Authors’ ReplyDear Editor,Moleiro et alFirst, Moleiro et alSecondly, the rationale for the addition of the Pereira suture is unclear. Moleiro et alI commend Moleiro et al


N = 70) derived from the use of Gamified Environments and Serious Games with people with Autistic Spectrum Disorder (ASD), identifying: authorship, nationality, publication period, topic, and design of the investigation. After that, the advantages and limitations observed are identified. Results indicate that most of them are focused on the design and testing of prototypes, (mostly) linked to the increase of social and emotional skills. The revision highlights that the game’s mechanics and dynamics  involve students from motivation. There is unanimous agreement to emphasize the positive impact of these resources to increment self-control, self-conscience, autonomy, and empathy.The aim of this study is to review the available research ( Kalantarian et al. , Arzone et al. , observing a tendency to seek resources to stimulate interpersonal relationships, increasing linguistic-communicative skills or autonomy as a whole. Adjorlu and Serafin  created for these people. Lee et al. , Gaudi et al.  socio-emotional, Dapogny et al.  linguistic, Silva et al.  design Sy et al.  create Jlls. And  socio-emNew Horizon to empower people in this group, reducing their stress and anxiety through mini-games which include gamification techniques. Elshahawy et al.  is also relevant, specifically linked to the stimulation of communication skills: on the one hand, associated with language skills, as pointed out by Gómez et al.  to increase sensitivity to gaze signals based on an immersive story that encourages interaction with animated characters and allows them to discover the usefulness of observing gaze signals to guide their behavior. In this same line, Scherf et al.  where the study areas are diverse. Bossavit and Parsons , Almurashi et al. (Finally, regarding studies focused on i et al.  and Jiméi et al.  conduct i et al.  focus oni et al.  study thi et al.  focus oni et al.  focus oni et al.  analyze i et al.  establisgamified environments in people with ASD, all the papers emphasize the great advantages of using the mechanics and dynamics of the game at the service of learning of people of this group, since an essential aspect of the success of the game is the attraction and motivation that lies beneath it (Malinverni et al., Regarding the The rules of the game, the visual rewards, the feedback, and the establishment of short-term goals involve the students in the game from their intrinsic motivation (Lee et al., Regarding the limitations observed in the gamified environments used in the interventions with these subjects, Lee et al.  point ouSerious Games in interventions with people with ASD, it is observed that these can be heterogeneous and used in various ways, favoring social interactions in several contexts and situations such as during the pandemic (Elshahawy et al., On the other hand, with reference to the use of Concerning the creation of SG, Terlouw et al.  indicateRegarding the limitations of the use of SG, Tang et al.  highlighAs future lines of research, and in accordance with Grossard et al. , it is n


Dear Editor,Effects of Plyometric Training on Physical Performance: An Umbrella Review”. We understand the substantial amount of work in doing such a review  and acknowledge its novelty. However, some methodological shortcomings may impact their results. Our aim is to provide constructive, methodologically based criticisms so that readers have the necessary information at hand to decide if the article by Kons et al. [Due to the relevance of plyometric training for the strength and conditioning community and the exponential rise in the number of original research and systematic reviews on the topic, an umbrella review is needed, as it summarises findings from published meta-analyses which could meaningfully advance knowledge in this field of research. We have read with great interest the work by Kons et al.  entitleds et al.  is justiLiterature search strategy. Kons et al. [s et al.  includeds et al. , the auts et al. –29 not is et al. . Moreoves et al. –37 were s et al. . Furthers et al.  selecteds et al.  above alInterpretation of published meta-analyses. Kons et al. [Although several meta-analyses investigated the effects of plyometric training on physical performance outcomes, most of them lack comparisons with control groups and are classified as low-to-moderate quality.s et al.  concludeFive meta-analyses compared the effects of intervention to control group, while the other 24 compared within-intervention-group effects.Moreover, the authors indicated:This seems an erroneous interpretation given that the control condition was part of the eligibility criteria for the umbrella review and, aside from one meta-analysis , all theInconsistent and erroneous data. Kons et al. [s et al.  provideds et al.  reporteds et al.  interpreWith this letter, we encourage researchers to conduct more comprehensive umbrella reviews in the future on the effects of plyometric training on physical fitness of individuals across the lifespan.Additional file 1: Table S1. Sections from the work of Kons et al. [


Rhythmicity is a fundamental characteristic of every living organism. It manifests itself at every level of an organisation, from structural and physiological changes to behaviour or cognitive processes. An evolutionarily dependent endogenous mechanism, in the form of a so-called biological clock, generates circadian changes in rhythmic processes independently of environmental conditions . A very Nutrients, titled ‘Circadian Clock and Nutrition’, aims to present further scientific evidence on the interdependence of the biological clock and nutrition. The first experimental study conducted by Verde et al. [This Special Issue in e et al.  containse et al. . The aute et al. , the aute et al. . In the e et al. , this ste et al. . The aute et al. . These ve et al. . The aute et al. . The aute et al. . The reve et al.  was inspNutrients.Therefore, to paraphrase the record in the Old Testament that “For everything there is a season and a time for every matter under heaven: a time to be born and a time to die; a time to plant and a time to pluck up what is planted. God has made everthing beautiful in its time”, it should also be assertively added that “there is also a time for eating”. This is the most general but very important conclusion of all the Special Issue articles in


Epilepsy is one of the most frequently encountered neurological conditions worldwide. The International League Against Epilepsy (ILAE) pointed out that epilepsy is a disorder of the brain characterized not only by recurrent seizures but also by its neurobiological, cognitive, psychological, and social consequences, emphasizing the long-term psychosocial issues and the high prevalence of psychiatric and behavioral disorders that are frequently more harmful than seizures themselves, worsening the quality of life in patients with epilepsy (PWE) . SeveralThis Research topic aimed to highlight basic, clinical, and translational research involved in studying epilepsy and its related neuropsychiatric disorders. A careful evaluation of all these aspects will contribute to optimizing therapy with a positive impact on seizure management, neuropsychiatric well-being, and quality of life in PWE.et al. [The review by Neri et al.  discusseet al. . Accordiet al. . Moreoveet al. [Concerning pharmacological treatment, Operto et al.  providedet al. [et al. [As widely reported in the literature, a PWE is more prone to develop psychiatric comorbidities, particularly depression . Such comorbidities are frequently more harmful to patients than seizures themselves, worsening their quality of life , 9. Suchet al. , several [et al. , antidep [et al. . Not sur [et al. , ASMs an [et al. . Clinica [et al. . In the  [et al. .et al. [et al.The review by Fortunato et al.  illustraet al. . The devet al. [The review by Rollo et al.  describeWe, the Guest-Editors, would like to express our gratitude to the many authors who contributed to this special issue: Epilepsy and Related Neuropsychiatric Comorbidities: Basic and Clinical Research.


P=0.97) different AM fungal quantification or change in image clarity. Therefore, the results of the present communication suggest that Parker blue and washable blue inks are alternative ink stains for the viewing and quantification of AM fungi in host cortical root tissues.Alternative methods for arbuscular mycorrhizal (AM) fungal colonized root staining have recently gained more attention for the reduction of hazard exposure to the user. Sheaffer blue ink has been employed for such an identification and quantification, having shown an increased degree of image clarity. However, sourcing Sheaffer blue ink is becoming problematic, leading to the need to find alternative inks that are readily available. Parker ink is a well-known brand, providing comparable colour options to Sheaffer. Two Parker inks, blue and washable blue, were employed alongside Sheaffer blue for comparative AM fungal colonized root staining. From quantified AM fungal vesicles and arbuscles, along with the degree of stained image clarity under microscopy, none of the inks utilized for this comparison produce a significantly ( All data pertaining to the present findings are contained within the manuscript.There have been many developments in host root staining for the identification and quantification of arbuscular mycorrhizal (AM) fungi . SheaffeTriticum aestivum) (n=15) was grown under controlled conditions for 4 weeks . Root staining was performed in accordance with Wilkes et al.  for both arbuscular (t-testing was not required, as no further significance could be determined.Single-factor ANOVA was able to show no significant difference between any blue inks used [buscular  and vesibuscular . Post-hoet al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [The present short communication has been able to provide indications that there is no discernible difference in AM fungal quantification between Sheaffer blue, Parker blue and Parker washable blue inks. Furthermore, as presented in et al. , Wilkes  [et al.  and Kowa [et al. . Yon et  [et al. , however [et al. , Wilkes  [et al. , or Kowa [et al. , whilst  [et al.  do not p [et al. . As the  [et al. . As show [et al.  and Wilk [et al. , Sheaffe [et al. .From AM fungal structures quantified and the clarity of micrograph images, no difference between ink brands was detectable. Therefore, the present communication can conclude Parker blue and washable blue inks are equally effective for quantifying and viewing root cortical AM fungal structures for the assessment of AM fungal–host symbiosis.


Cancers [In his Comment  on our rCancers , Dr. YafDr. Yaffe points out that there is little if any evidence for self-selection bias in the Canadian study of Coldman et al. . This do


Coincet al.  present et al. . We conc. 1.1et al. [Foster et al.  focus onet al. . Other set al. ) highliget al. ,7 and seet al. ,8,9) supUneven sampling in the fossil record is omnipresent and well known. Observed extinction records are often smeared back in time, more so for some organism groups than others, and the record of each mass extinction varies by the geography of its exposed outcrops  –12. Such. 1.3et al. [Phylogeny remains one of the strongest predictors of extinction  and covaet al. . Groups et al. , which met al. ,15).et al. [within an event only just meet this mark . These values should become the practical benchmark for the best between-event prediction that could be hoped for. If a model trained on random observations of extinction variation at an event struggles to provide a good prediction for extinction variation within the same event, then the conclusion must be that fossil data are difficult to predict from per se. The mean across the six between-event AUC values in Foster et al. [The benchmark for successful predictability depends on context and discipline. Foster et al.  use the r et al.  was 0.62r et al. ,17).. 1.5et al. [Foster et al.  judged pet al. ,18,19 anet al. ,20).et al. [Evolutionary and Earth system changes are components we must account for in hypotheses of cause-effect, as Foster et al.  fittinglet al. ,8. This . 2et al. [We congratulate Foster et al.  on a sopet al. ,19, alonet al. ,21 and tet al. , and theet al. . The fos


Horses hold an important place in many human societies with a role that has changed considerably over time from beast of burden and meat (and later milk) source, via transportation means, to leisure activities and even financial speculations today. It is therefore no wonder that horses also attract the interest of investigative geneticists. The recent literature provides new insights into the genetic history of horse domestication. In an article published last month, Achilli et al.  studied et al. , indicatet al. . Strikinet al. . Is this [et al.  appear t [et al.  investig [et al.  (althoug [et al.  have now [et al.  performe


Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential.The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various  Cycas circinalis) flour to make tortillas, soups and dumplings by the native Chamorro people [Medical research attention was drawn towards Guam in 1953 when it was reported that the incidence of an amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) within the local Chamorro people was 100 times higher than the rest of the world ,3. The uo people ,5, couplo people , led to o people .In 1967 Vega and Bell  isolatedet al. correlated elevated incidence of ALS in communities in the Kii peninsula of Japan [et al. [et al. [Despite this observation, little attention was paid to BMAA until 1987, when Spencer of Japan  and Iriaof Japan  to the tof Japan . The groof Japan . This wa [et al. , who sug [et al.  who calc [et al. .et al. [In 2002, Cox and Sacks  rejuvenaet al.  compiledet al. , supportet al. [et al. [At this point in time the source of BMAA in cycads was unknown. In 2003 Cox et al. . Cyanobaet al. ,23. The  [et al.  have suget al. [et al. [post mortem brain samples in 2009 [et al. [et al. [et al. [N-hydroxysuccinimidyl carbamate method used by Murch et al. [et al. might explain the lack of detection.In 2003, studies conducted by Banack and Cox  showed tet al.  detectedet al. . These bet al. . In thiset al. . HPLC anet al. ,27. Thes [et al.  conducte in 2009 . These o [et al.  with a c [et al. ). The di [et al. ,29 have  [et al. ,31 to beh et al.  is more h et al. , and is h et al. . Instabiet al. [et al. [In 2006 Banack et al.  tested v [et al.  detectedet al. [Nostoc species produce BMAA, proving that it could be produced globally. The ubiquitous nature of cyanobacteria means that given the right conditions, bioaccumulation of BMAA could potentially occur in any of the greatly varying environments in which cyanobacteria are found [in vivo uptake of BMAA by the aquatic macrophyte Ceratophyllum demersum in an experimental system [Daphnia magna [In 2007, Banack et al.  employedre found . This prre found , as wellre found . BMAA hare found , and in re found . The potl system , and bioia magna .2+, K+, Na+, Mg2+ and Cl− [N-methyl-d-apartate (NMDA) and metabolic glutamate receptors (mGluR), all of which are activated by glutamate and similar substances. A review by Doble [Excitatory amino acids (EAAs) act as neurotransmitters within the nervous system . Their a and Cl− . Malfunc and Cl− . Excitot and Cl− . The maiby Doble  explaineby Doble –50.et al. [et al. [et al. [et al. [et al. [et al. [post euthanasia failed to find any evidence of neurochemical or neuropathological changes in the any of the sample animals [-Aguado et al. [et al. [-Aguado et al. [et al. [With substantial and ever growing evidence that BMAA does play a role in the onset and progression of neurodegenerative diseases, the most important question is; what mode of activity does BMAA exert? Although BMAA had not yet been discovered, Dastur  fed cycaet al. ,53 also  [et al. , with ad [et al.  was repo [et al.  and 1993 [et al.  produced [et al.  fed high animals . Similaro et al.  fed 28 mo et al. . In the o et al. , the aut [et al.  to obsero et al. , as poss [et al.  that thein vitro when a physiological concentration (10 mM and above) of bicarbonate (HCO3−) ions were present in the media. This discovery was soon followed by Richter and Mena’s [3− was required for BMAA activity to occur. Follow up experiments showed that BMAA could bind to NMDA and non-NMDA receptors on mouse cortical neurons [3− was a critical discovery as it greatly affected the results of experiments conducted using freshly isolated tissues where experimental reagents are generally simple and defined, and often did not contain HCO3−. Using these leads Myers and Nelson [in vitro assays.The first mechanistic BMAA research was performed in 1988 when Weiss and Choi  discoverd Mena’s  observatd Mena’s , that HC neurons . The depd Nelson  identifiet al. [et al. [in vitro assays. Brain slices and mixed primary cultures taken from 8-day old rats were exposed to BMAA at 1 mM in conjunction with various neural metabolites and antagonists of NMDA. Their results indicated that BMAA acts as a mixed agonist of metabotropic and NMDA receptors, and as seen in other studies, BMAA activity was enhanced by the presence of bicarbonate ions at 25 mM [et al. [et al. [et al. [et al. [post administration. They also demonstrated that BMAA is taken up into the brain by the large neutral amino acid carrier of the blood-brain barrier, which suggests that uptake may be sensitive to the same factors that affect neutral amino acid transport such as diet, metabolism, disease and age [In 1990 Lindström et al.  gave int [et al.  conducteat 25 mM . The gro [et al.  and Mats [et al.  performe [et al. . The 199 [et al.  reported [et al.  demonstr and age . In esseet al. [2+ in the presence of BMAA (5 mM) with or without HCO3− ions. This experiment indicated that there was a small increase in intracellular Ca2+ concentration with BMAA only, but a large increase when BMAA and HCO3− were added together. This further supports the belief that BMAA is dependant on HCO3− as a cofactor and that the correspnding β-carbamate is the active compound. It also suggests another potential mechanism of activity as impairment to intracellular calcium homeostasis has been shown to cause disruptions in Ca2+-dependant cascades that lead to neuronal cell death and neurodiseases [Brownson et al.  assayed diseases ,72.et al. [Haemopis sanguisuga after treatment with BMAA (100 μM–10 mM) and HCO3− (20 mM). A significant reduction in input membrane resistance was measured, indicating that BMAA depolarizes the cell by increasing membrane permeability and conductance.The study of Nedeljkov et al.  measuredpost exposure. This study showed that BMAA caused injury to hippocampal neurons. They also demonstrated that BMAA increasingly caused a degree of cell death in NSC-34 cells  as the amount of BMAA administered increased from 100 μM up to 1 mM. A study conducted by Lobner et al. in 2007 [+. This observation holds great significance determining that very low concentrations of BMAA (orders of magnitude lower than previously thought) can potentially cause serious neurological damage if other factors are involved. This study also showed that BMAA has three-fold activity by causing excitotoxicity on NMDA and metabotropic glutamate receptor subtype 5 (mGluR5) receptors, and via oxidative stress. This supports the notion that BMAA may play a role in a variety of different neurodegenerative conditions. Rao et al. [2+ concentrations and the generation of selective reactive oxygen species (ROS) in motor neurons, with minimal effect on other spinal neurons. Liu et al. [et al. [−, leading to glutathione depletion and oxidative stress [in vitro. It is worth noting that this product was not formed in brain tissues in this study. This provides evidence of yet another method of toxicity by BMAA, although the test dose is potentially too high for the result to be environmentally significant. Production of methylamine is significant as it has been shown to produce a state of oxidative stress in rats [et al. [post injection. The results showed that BMAA interacts/binds with melanin, particularly during its synthesis, and increasingly bioaccumulates in melanin and neuromelanin-containing cells over time. The authors proposed that this may provide a link between BMAA and the PDC symptom of pigmentary retinopathy [et al. [in vitro membrane potential depolarization of leech nerve cells by action on non-NMDA ionotropic glutamate receptors. A concomitant increase in cell membrane input conductance, as well as an increase in Na+ activity and a decrease in K+ activity was noted. This indicated that, in addition to AMPA/kainite receptors, BMAA could initiate excitotoxicity through the activation of other non-NMDA ionotropic glutamate receptors. In 2009, Santucci et al. [post administration. Increases in retinal neuron death and the production of ROS were observed in this study. Also in 2009, Purdie et al. [In 2007, Buenz and Howe  intracra in 2007  showed to et al.  concludeu et al.  validate [et al. , as welle stress . In 2009e stress  found th in rats . In 2009 [et al.  injectedinopathy . Also in [et al.  showed ti et al.  injectede et al.  exposed et al. [2+ and a massive release of cytochrome-c (cyt-c) into the cytosol. This study also demonstrated that activity was predominantly mediated via mGluR1 receptors. These observations indicate disruption to mitochondrial activity, excitotoxicity, and induction of apoptosis induced by exposure to BMAA. More recently Karlsson et al. [in vivo. Summaries of both in vivo and in vitro investigations into the bioactivity of BMAA are presented in In 2010, Cucchiaroni et al.  found ran et al.  injectedn et al. . Most ren et al.  exposed n et al. . It shouet al. [et al. [et al. [d-glucoside (BSSG) is suggested to play the same proposed role [When reviewing BMAA literature it quickly becomes clear that there are large differences in opinion. When Borenstein et al.  proposedet al.  raised d [et al.  indicate [et al.  claimed  [et al.  has beensed role . Varioussed role ,91. Inte+ [2+ [+ [− [− increases the release of glutamate from the cell  that BMAA plays in neurodegeneration. Karamyan and Speth have reviewed the available literature on the evidence for and against the involvement of BMAA in the development of ALS/PDC . They coet al.  were alset al. [When considering all the published data, it appears certain that BMAA can contribute to the onset and progression of neurodegenerative disease in certain susceptible individuals. It would be useful to focus on better understanding the proposed mechanisms of BMAA activity, as well as identifying new as yet undescribed mechanisms that might play an important role in the overall potency of BMAA. Without a sound understanding of how BMAA truly works, it is impossible to predict the level of risk it poses with any significant degree of confidence. One question posed in the review by Karamyan and Speth  that is et al.  when theet al. , this po


Sir,et al[et al.[I read the article entitled, “Percutaneous endoscopic colostomy: A new technique for the treatment of recurrent sigmoid volvulus,” with greet al describeal[et al. had alsoal[et al. Althoughal[et al., it is nal[et al. Major coal[et al. also neeal[et al.


Science, Salimpoor et al. (In a recent issue of r et al.  reportedr et al.  demonstrr et al.  where thr et al. . Nonether et al. . For insr et al. . We sugg


Besides connexins, another group of proteins, the pannexins, showing many molecular similarities with connexins have been identified. They seem to form hemichannels which may regulate cytosolic homeostasis or the release of small molecules. The present issue provides a comprehensive picture of recent developments and current research in this fascinating, fast developing area comprising review and original research articles on both connexins and pannexins written by leading experts in their research areas. The articles are organized in three parts:n et al. . Verheuln et al.  shed lign et al. . With ren et al.  review tn et al. -are exprr et al.  investigr et al. . In the r et al.  or with r et al. . The secr et al.  and a ner et al. .Part B starts with an original article about pannexin 1 elucidating the problems with Panx1 knock outs and showing the generation of astrocyte and neuron-specific Panx1 deletions (Hanstein et al., Part C focuses on the role of gap junctions in various diseases starting with an interesting hypothesis article by Végh et al.  on the rThis compilation of articles on most recent developments in connexin and pannexin research hopefully encourages more scientists to investigate these highly interesting cell biology mechanisms in their research areas. When cellular interaction or interplay is of relevance this recent research suggests: mid the gap!


Dear Editor,The article by Mogadam et al.  regardin


To the Editor: Xing et al. (Phlebovirus (


Radiofrequency ablation in the management of advanced pancreatic cancer should be no longer utilized in patients with locally advanced or metastatic pancreatic adenocarcinoma. Spiliotis  about ouet al. , no stanet al. . This opet al. . In thiset al. . Using t


Acta Cryst. (2010), E66, o3315.Corrigendum to  et al.  is corrected.The correspondence author in the paper by Jia


Dear Editor,Hereditary hemochromatosis (HH) is the most frequent genetic disease in populations of European origin. The HH gene was cloned by Feder et al. in 1996, and 2 major mutations were discovered: C282Y and H63D. Geographical differences with mutation frequencies have been published [Jowkar et al.  have recJowkar et al. , with th


The Indian Journal of Psychiatry published three articles in its first issue way back in 1958. Since then, it has steadily published more than 200 papers on one or the other aspect of schizophrenia. From rudimentary research methodology and descriptive approach, schizophrenia research, as published in the Journal, seems to have come of age with more and more sophisticated research designs and methodologies. Our ardent researchers have made significant contributions in the understanding of this riddle called schizophrenia. Notable contributions have been made in the field of epidemiology, course and outcomes and phenomenology of this disorder. However, research in psycho-social rehabilitation of schizophrenia and related areas is sparse and sporadic. The need to conduct research that impacts health policies and planning of services for this disorder is evident and our researchers would do well to provide impetus in these areas. The Indian Journal of Psychiatry has come a long way from its humble beginning with the publication of its first volume in October 1958. The inaugural issue had three articles on schizophrenia, the first, an Editorial Annotation titled “Tranquillizers” by Dr. Kirpal Singh, which drew attention to the phenomenon of “market being flooding with numerous so called tranquillizers,” though Dr. Kirpal Singh observed even at that time that the efficacy of these and relative superiority of any one of these were questionable. The thirAnnotation of research in various aspects of schizophrenia published in the Indian Journal of Psychiatry, since its inception, follows the above mentioned prelude. We have adopted a descriptive approach, describing the research published in our Journal and offer comments on the research efforts where appropriate.The articles published in the Journal in the 1960s were an assortment of publications related to the etiology, clinical aspects, treatment and, course and outcome of schizophrenia.Evident from the writings of the sixth and seventh decades of the last century, psychodynamics and psychotherapy had important places in the field of schizophrenia. However, no significant research endeavors were made to study the dynamics of schizophrenia in a systematic manner. Rao the onlyTeja showed tBiological experiments conducted elsewhere started finding mention in the abstracts by eminent Indian psychiatrists. Kirpal Singh providedA paper by Deb gave aptNarayana Murthy studied Clinical observations rather than ‘trials’ were the main basis for guiding management of patients with schizophrenia. Catatonia was thought to be aggravated by Rauwolfia and/or Largactil.An eight-week placebo controlled study of prochlorperazine carried out by Menon in 20 feDutta Ray and Kapur conducteThe research publications of the 60s are creditable for various reasons. Even though research tools and funding were not available and though the research mostly followed a descriptive paradigm, it is praiseworthy that people even then had enthusiasm and enterprise. These publications are now of historical value contributing richly to the history of psychiatric research in our country.Prabhu and Ramchandran in a samet al.[et al.[Cytogenetic scientists conducted research on dermatoglyphics in schizophrenia and found that the patients had higher indices as compared to normal controls. Eswaraiaet al. found lyet al. studied et al. studied l.[et al. (1976) set al.[A family study detecting psychiatric morbidities in family members of schizophrenia patients was carried out in a sample of 500 patients by Sethi et al. Though cBhaskaran and Saxena comparedet al.[Akhtar et al. attempteet al.[Singh et al. construcet al.[et al.[et al.[Varma et al. studied l.[et al. Abraham l.[et al. used Repl.[et al. studied et al.[et al.,[et al.[Therapeutic efficacy of thiothixene was compared to five phenothiazenes in 60 chronic schizophrenia patients by Kishore et al. Prochloret al. Mahal anet al. used Briet al. Sharma aet al. Bagdia e.[et al., conducte.,[et al. conducteet al.[et al.,[Clinical trials of depot preparations had begun in the 70s. A trial of fluphenazine enanthate of four-week duration with a follow-up of eight weeks was carried out by Bagadia et al. involvinet al. in 112 l.[et al., but withControlled trial of multiet al.[rd of the patients were followed up and outcome was defined a priori; a positive relation was found between good prognostic factors and outcome. Sarada Menon and Ramachandran[In a, longitudinal study  tachandran comparedRastogi and Mahal46 studieMazumdar and Sinha conducteVarma studied et al.[Bhaskaran et al. studied The research carried out in the 70s failed to adhere to a rigorous methodology, compounded by the fact that diagnosis of schizophrenia lacked reliability. Dermatoglyphics and phenomenology dominated research efforts. However, there was no unifying trend in the research carried or reported.et al.[Padmavathi et al. (1988) cet al.[et al.[et al.[et al.[et al.[Various studies were reported in the Journal in search of biological markers and diagnostic tests in schizophrenia. Kondaiah et al. found thl.[et al. found thl.[et al. and Tiwal.[et al. found inl.[et al. observedl.[et al. and no dl.[et al. and no dl.[et al. Chatterjl.[et al. studied l.[et al. who founet al.[The soft neurological signs (SNS) and minor physical anomalies (MPA) were studied in 107 adult schizophrenia patients by Nizamie et al. SNS wereet al.[Sethi et al. conducteet al. studied et al. Some genet al. The propet al. Jangid aet al. comparedet al.[Jayaswal et al. studied et al. studied the phenomenology of delusions in 112 patients with schizophrenia using the Present State Examination. The authors found that the delusions of persecution were more common in males and those above the age of 30 years. Educated patients had more delusions of reference, delusional misinterpretation and delusions of thoughts being read. Also, systematization was seen more in younger patients, while married patients had more delusions of reference. Kulhara et al. presented the usefulness of the Brief Psychiatric Rating Scale (BPRS) in positive and negative sub-typing of schizophrenia as significant differences emerged between the two sub-types on items like emotional withdrawal, guilt feelings, tension, hallucinatory behavior, motor retardation, blunted affect and excitement. Also, Kota and Kulhara[et al.[Kulhara d Kulhara used a cra[et al.. Signifiet al.[Mazumdar et al. assessedRamanathan studied A study comparinet al.[Kota et al. carried et al., high scet al.et al.[The child-rearing attitudes and personalities of 100 pairs of parents of patients with schizophrenia of either gender were compared with controls and significant differences were found on variables like irritability, suppression of anger, suppression of sex, avoidance of communication etc.83 Suman et al. studied et al.[Trivedi et al. studied et al.[Compared to families of patients with chronic lung disease, the families of the patients with schizophrenia felt greater burden in the areas of finance, family leisure, family interaction and mental health of other family members according to a study by Gautam and Nijhawan. Mubarak et al. found noAs in the last decade, drug trials of various oral and depot preparations of antipet al.[A comparative study showed net al. with thret al. studied et al. found inet al. observedet al.[et al.[Verghese et al. reportedl.[et al. studied et al.[Kulhara et al. examinedet al.[et al.[Nagaswami et al. studied l.[et al. found thBiological and phenomenological investigations dominated research in the decade of the 80s. Biological research was mostly directed towards replication of the research findings of the West although it did not match research sophistication and the technical fastidiousness of the Western researchers. Nonetheless, our pioneering researchers in this area were able to generate research funding, thus, forcing research funding agencies to take a more benevolent attitude towards research in mental health. Phenomenological research carried out during this period on the other hand had more sophisticated research designs, trusted and tested research instruments and adherence to some or the other operationalized criteria for the diagnosis of schizophrenia.Phenomenology research in this era brought comparative or transcultural psychiatry in sharp focus, compelling outsiders to take serious notice of similarities as well differences in phenomenology between the East and the West. Course and outcome studies provided the much needed independent support to “better outcome” hypothesis. Despite the publication of a few studies, research in psychological, psychosocial and rehabilitation aspects of schizophrenia continued to be neglected areas. Drug trials were few but had improved research designs and assessment though the numbers of patients studied in these trials were modest. ECT research had few dedicated workers and their research output is commendable.et al.[As part of the World Health Organization (WHO) collaborative study, two geographically defined populations in urban and rural Chandigarh (North India) were monitored for a period of two years. The annual incidence rates obtained were 4.4 and 3.8 per 10,000 for the rural and urban areas respectively. As part et al. found anet al.[et al.[et al.[et al.[et al.[et al.[et al.[et al.[As in the previous decade, Jhingan and Munjal studied et al. studied et al. and Ponnl.[et al. in famill.[et al. found thl.[et al. found sil.[et al. and no dl.[et al. also foul.[et al. studied l.[et al. Agarwal l.[et al. conducteet al.[et al.[et al.[Ananthnarayan et al. studied l.[et al. studied l.[et al. used theet al.[et al.[Neuroimaging had begun to be used as a research tool by this time. Siddhartha et al. studied l.[et al. studied et al.[Somanath et al. conducteThus, research in India reflected the drive to find biological markers of schizophrenia in common with elsewhere in the world. Improvement in methodology; use of advanced techniques, comparatively larger sample size were also visible.et al.[With revisions of classifications, more emphasis was laid on delusions and hallucinations for diagnosis of schizophrenia. Singh and Kulhara presenteet al. carried et al.[et al.[et al.[Borde et al. reportedl.[et al. comparedl.[et al., the frel.[et al. studied l.[et al. found thet al.[et al.[et al.[Giridhar et al. found a l.[et al. examinedl.[et al., who repOn Luria - Nebraska Neuropsychological Battery (LNNB), schizophrenia patients performed better than brain damaged patients but worse when compared to normal controls. The findet al.[In a five-year follow-up study, Verghese et al. found thThara and Rajkumar studied et al.[et al.[et al.[et al.[Among families of long-term psychiatric patients, Roychaudhuri et al., found tl.[et al. assessedl.[et al. comparedl.[et al. assessedet al.[et al.[Padmavati et al. developel.[et al. devised Thara and Srinivasan studied et al.[et al.[Borde et al. attemptel.[et al. in a conet al.[et al.[et al.[et al.[Towards the end of the decade, newer antipsychotics (second generation) had made entry. In small open trials of risperidone, the drug was found to be both efficacious and safe.–149 Singet al. in a doul.[et al. studied l.[et al. in treatl.[et al., in a grl.[et al. while Srl.[et al. reportedl.[et al. reportedet al.[As in the previous decade, researchers began examining the side-effects of antipsychotics. Ravi et al. found thet al. conducteet al. reportedet al.[et al.[Chauddury et al. found thet al. examinedl.[et al. and it wEpidemiological work in the 90s established incidence and prevalence rates for schizophrenia in our country, which has been a very significant contribution of this era and has impacted health policies and planning of delivery of mental health services. Biological research continued its directionless replication-oriented path without much impact. Phenomenological research continued in a sound way and had varied topics from clinical descriptions to insight and the like. Course and outcome research consolidated the gains of 80s and attracted national and international attention. Clinical psychological assessment research took a back seat though research in psychosocial and rehabilitation aspects flourished. Introduction of “second generation antipsychotics” ushered in a wave of drug trials that is still pulsating. Clozapine and “treatment resistant schizophrenia” were studied more energetically and with better research designs.et al.[et al.[et al.[et al.[Like in the previous decade, researchers across the country continued to perform research on various metabolites and hormones. Anand et al. measuredet al. Dadheechl.[et al. studied l.[et al. comparedl.[et al. studied et al.[et al.[et al.[Using neuroimaging and functional imaging, Raju et al. carried et al. studied l.[et al. studied l.[et al. examinedl.[et al. carried et al.[et al.[Malhotra et al. using SPl.[et al. studied et al.;[In children of schizophrenia patients, neurobehavioral functioning, social behavior, cognitive function, attention and intelligence were assessed by Shah et al.; with moret al.[Singh et al. investiget al.[et al.[et al.[Tharyan and Sarvanan studied et al. found noet al. found thl.[et al. and no dl.[et al. assessedet al.[et al.[The demographic and clinical correlates of substance abuse in schizophrenia were assessed by Aich et al. The subset al. found thl.[et al. found thet al.[et al.[Sabhesan and Parthasarty studied et al. found a l.[et al. found thet al.[et al.[et al.[et al.[et al.[The Quality Of Life (QOL) was assessed by using WHOQOL- BREF in 50 patients by Solanki et al., who fouet al. assessedl.[et al. studied l.[et al. revealedl.[et al. found thl.[et al. assessedet al.[et al.[Thomas et al. found a l.[et al. also stul.[et al. assessedet al.[et al.[et al.[Jagadisha et al. found thl.[et al. conductel.[et al. who founl.[et al. assessedl.[et al. found thet al.[et al.[et al.[As in the previous decade, trials with newer antipsychotics continued. Shrivastava and Gopa conducteet al. comparinl.[et al. comparedl.[et al. of 6 weel.[et al. of 2 fixl.[et al. carried et al.[Raguraman et al. evaluateet al.[With the recognition of obsessive-compulsive symptoms in schizophrenia, Agarwal and Agarwal carried et al. evaluateet al.[Most of the trials were open label trials, with small sample size, with short durations of follow up. Dutta et al. observedet al.[Goswami et al. carried et al. ECT showet al.[Shriharsh et al. conducteet al.[et al.[Ponnudurai et al. followedl.[et al. studied International trends of research in biological aspects were mirrored in research publications of this decade. Neurotransmitter research, neuroimaging, PET scanning, EEG, oxidative stress and antioxidants were investigated and reported with varying degrees of success and impact. Research interest in phenomenology and psychopathology dwindled but “dual diagnosis” i.e. the interface between substance dependence and schizophrenia evoked research fancy of few. Psychometric research had few takers, though enthusiasm in psychosocial and rehabilitation aspects was evidenced by increased number of research publication in these areas during this time frame in question. Drug trials flourished, ECT research declined and other interventions did not attract many researchers.From this descriptive annotation it is evident that Indian researchers have meaningfully engaged themselves in schizophrenia research. Phenomenology, clinical and psychosocial variables in schizophrenia are the main strengths of Indian research as reported in our Journal. Of late, coping strategies, stigma and caregiver issues have also emerged as areas of study interest. Significant contribution has been made by Indian researchers in the field of prognosis, course and outcome of schizophrenia that has caught the awareness of the whole world fuelling debate whether or not outcome is genuinely better in the Indian context. Good quality but sporadic biological research in schizophrenia by Indian workers is also documented but cutting edge research in this area still eludes us. Operational research and psychosocial intervention researches are still lagging behind and our talented researchers need to make a move in these areas. Sound research in these areas, complimented by research in health economics of schizophrenia, will impact health policies and delivery of healthcare to this underprivileged, ignored and unfortunate group of patients and their ever so Social caregivers.


The theme of the 2012 International Conference on Bioinformatics (InCoB) in Bangkok, Thailand was "From Biological Data to Knowledge to Technological Breakthroughs." Besides providing a forum for life scientists and bioinformatics researchers in the Asia-Pacific region to meet and interact, the conference also hosted thematic sessions on the Pan-Asian Pacific Genome Initiative and immunoinformatics. Over the seven years of conference papers published in BMC Bioinformatics and four years in BMC Genomics, we note that there is increasing interest in the applications of -omics technologies to the understanding of diseases, as a forerunner to personalized genomic medicine. BMC Bioinformatics and BMC Genomics Supplements have been summarized by Schönbach et al.[BMC Bioinformatics [BMC Bioinformatics [Since 1998, the Asia-Pacific Bioinformatics Network (APBioNet) [ch et al., along wormatics . With thormatics . A detaiormatics .th International Conference on Bioinformatics [APBioNet's 11ormatics  was heldInCoB2012 hosted a special forum, organized by PAPGI researchers. PAPGI, formerly known as the Pan Asian SNP Initiative (PASNP), is a collaborative project that strives to explain the Pan Asian continuous spectrum of phenotypic traits by deciphering the underlying population genomic diversity. In 2009, the consortium published the fundamental prediction of Asian migration history  using thDuring the discussions, several issues including ratification of consent agreement, sample selection criteria, collaboration with other countries/societies and external funding were raised. In particular, PAPGI will be officially affiliated to the Human Genome Organization (HUGO). The affiliation to the Asia Pacific Society of Human Genetics is being finalized. Since the samples used in PAPGI may be different from the ones used in the previous PASNP study and there are more countries, mainly from the Middle East participating in the project, issues about sample selection criteria was discussed and a general guideline for PAPGI sample selection will be drafted.BMC Bioinformatics Vol. 13 Supplement 17 [Of the 53 accepted proceedings papers 25 articles were published in the et al. [et al. [et al. [et al. [Piriyapongsa et al.  present  [et al.  have pre [et al.  have car [et al.  have dev [et al.  is a new [et al. .et al.[et al. [et al. [et al. [Garg and Ranganathan  have devet al. present .[et al.  have rep [et al.  have sys [et al.  have uncet al. [Burkholderia pseudomallei, a soil bacterium which causes the disease melioidosis. Yang et al. [et al. [et al. [Khoo et al.  report tg et al.  have prog et al.  while mig et al. . Lee et  [et al.  have dev [et al.  have anaet al. [et al. [et al. [Ali et al.  have dev [et al.  report m [et al.  report pet al. [et al. [Kumar et al.  have eng [et al.  have preet al. [Praneenararat et al.  present et al.  have uncet al.  has compet al.  have ideet al. [de novo next-generation sequence assembler. An application of modern genome informatics to marine ecosystems is reported by Somboonna et al. [To leverage on the newly developed cloud computing technology, Chang et al.  have deva et al. , in theiet al. [et al. [BMC Bioinformatics supplement.The best paper title was awarded to Li and Li for their advancement of disease gene identification using a new random walk model that allows cross-walking between phenotype and gene networks . The runet al.  and Abba [et al. , in the http://ictbi.imed-cn.org/) in Taicang, China. To follow the rising interest in biomedical and translational bioinformatics InCoB2013 will be hosted jointly with the 2nd ICTBI and is scheduled to be held September 18-21, 2013 in Suzhou, China. We also hope to support PAPGI session, bringing population genomics together with translational bioinformatics, in the quest for personalized genomics.APBioNet participated recently in the 1st International Conference in Translational Biomedical Informatics (ICTBI; The authors were organizers, co-chairs, and/or session chairs of InCoB2012. TWT is a founding Director of Asia Pacific Bioinformatics Network, Ltd. All authors declare they have no other conflict of interest.SR and CS wrote this editorial. SR, ST, TWT and CS served as co-editors for the InCoB2012 supplement issues with SR as the lead editor. CS and SR managed the manuscript submission, peer-review and editorial decision processes as superchairs of EasyChair Conference System.


Dear Editor,We read with interest the paper by Pawlowska et al.  and we w


We appreciate the interest of Pigatto et al. in our review . We undeNone of the studies mentioned by Pigatto et al. in their letter  includes


Dear Editor,et al. [et al. [et al [In their letter to the editor, Egeland et al.  criticizet al. , and pro [et al.  are not  [et al. , is math. [et al  uses theX = x) applies to 'alleles to change by adding or subtracting an absolute number of x repeat units'. Hence, by definition x > 0, and as noted just after equation 8 'equal probabilities for gaining or losing repeats are assumed', it is incorrect to multiply the geometric terms by a factor of 2, as Egeland et al. have done [X ≠ 0) becomes μ, by summing the individual terms over all non-zero positive integer values of X. In addition, we are not the first to use such formulations of a mutation model. Estoup et al. [et al. [et al. [First, the mutation model, explained by equation 8 of page 5 of our paper , clearlyave done . Followip et al.  used exa [et al. ). Both oa or >b, for some arbitrary allele sizes a and b, defined by the smallest and largest sizes of alleles found at a locus in worldwide surveys , with α = 0.95 and μ = 10-4, the chances of zero or negative allele sizes occurring by mutation is 1.25 × 10-7, an order of magnitude smaller than that suggested by Egeland et al. [et al. [Second, it is true that this mutation model allows for production of zero or negative repeat sizes of alleles. This is also true for the simple stepwise mutation model (SMM ), in whialleles' -11). The reports  suggest et al. [et al. [φ(x)dx, meaning that there are φ(x) many alleles with allele frequency in the range of . However, these allelic states have a 'wandering' nature, because of the continual new introduction of mutations. Published research starting from the early 1990 s and continuing to the present day support some form of a generalized stepwise mutation model as an approximation of the governing mutation model for STR loci [et al. [Third, Egeland et al.  claim th [et al. , does no [et al. ), and he [et al. ,14. Beca [et al. ,15. The STR loci ,8,16-18. [et al. ,21 as su [et al. , withoutApart from such statistical support of stepwise mutation models for STR polymorphisms, there is also empirical support for the occurrence of such mutations, as seen from compilations of experiences of mutational observations in parentage testing laboratories . Such daet al. [i) is inversely related to its frequency (πi). This, together with the lack of any stationary frequency distributions of alleles labeled by allele sizes, make that mutation model unrealistic and inapplicable to STR loci such as those used in DNA forensics, and probably for other microsatellite loci as well. We should also note that the most widely practiced adjustment of population substructure effects on allelic/genotypic diversity at STR loci [In addition to statistical support for such mutation models, the compilation of observed mutations at the forensic STR loci  reveals et al. ), which STR loci , as usedSTR loci , is alsoSTR loci . This apSTR loci , and ouret al. [We have one last point to make. Although not mentioned by Egeland et al. , we founet al.  while pret al.  represenet al. [et al. [In conclusion we contend that in absence of any definitive mechanism of mutation models experimentally shown to explain all mutations at STR loci, any mutation model can only be an approximation and hence, the two-phase mutation model described in our paper  cannot bet al.  less rea [et al.  assertinThe authors declare that they have no competing interests.RC and JG wrote the manuscript. All authors contributed to the contents, read and approved the manuscript.


Acta Cryst. (2011), E67, o1861.Corrigendum to  et al.  is corrected.The name of one of the authors in the paper by Al-Salahi


Dear Editor,We read with interest the article by Abu El Makarem MA et al.  entitled


Acta Cryst. (2013), E69, o187.Corrigendum to  et al.  is corrected.The title in the paper by Elgemeie


BMC Medical Genomics that includes16 papers selected from the 2011 World Congress in Computer Science, Computer Engineering, Applied Computing as well as other sources with a focus on genomics studies with a focus on human diseases.This is an introduction to the supplement to  BMC Medical Genomics with manuscripts selected from this congress as well as invited submissions. More than 30 manuscripts were submitted to this supplement. Each manuscript was reviewed by at least two reviewers in addition to the review by the editorial board. We hope that the selected 15 manuscripts represent the current success and challenges of medical genomics research and indicate the future direction.This supplement is dedicated to the World Congress in Computer Science, Computer Engineering, and Applied Computing on July 18-21 in 2011 in Las Vegas, Nevada. The congress drew a wide attention from computer scientists, applied mathematicians and statisticians, bioinformaticians, and researchers in many other fields. As one of the fastest developing fields, genomics became a prominent area that drew attentions from most attendants. Noting that a substantial part of genomics work was dedicated to human disease studies, we decided to launch a supplement to et al. [et al. [The genetic heterogeneity and the complicated molecular mechanism underlying tumor progression have made it highly difficult to develop sustainable approaches for cancer therapy. The explosion of knowledge about global gene alterations and genomic variations has changed the traditional approaches of cancer research and presented a promising foundation for diagnosis and treatment of cancer. Much effort of this supplement is devoted to cancer research with various types of genomics data in terms of early diagnosis, biomarker identification, cancer classification and therapy. Wang et al.  proposedet al.  also expet al.  for breaet al. . His met [et al.  proposedet al. [et al. [et al. [Gene pathway and networking is another major focus of this special issue. Garrett et al.  investig [et al.  to inves [et al.  identifi [et al.  comparedet al. [et al. [et al. [et al. [The manuscripts of this supplement cover various data types and broad topics. ChIP-Seq of RNA Pol II was used to identify the bidirectional promoter by detecting bi-peak shapes using computational approach . Qureshiet al.  investig [et al.  develope [et al.  proposed [et al.  develope [et al.  using neIn short, this special issue brings forth many exciting scientific discoveries and methodology advances that present the cutting edge development of genomics research in human diseases. We hope that it would provide guidance for the questions and attempts in current genomics research and stimulate ideas for future studies.The authors declare that they have no competing interests.


Two references cited in this article were incorrect. The reference to Ingram et al. (1996) should instead be Page et al.  and the


Acta Cryst. (2010), E66, o3033–o3034.Corrigendum to  et al.  is corrected.The name of one of the authors in the paper by Adam


Acta Cryst. (2010), E66, o3020–o3021.Corrigendum to  et al.  is corrected.The address of three of the authors in the paper by Shahani


Journal of Immunology, Bauernfeind et al.  as well as endogenous damage-associated molecular patterns (Kolliputi et al., d et al.  present d et al.  conducted et al.  showed td et al.  as they d et al.  has shed


Structural genomics projects have solved many new structures with unknown functions. One strategy to investigate the function of a structure is to computationally find the functionally important residues or regions on it. Therefore, the development of functional region prediction methods has become an important research subject. An effective approach is to use a method employing structural and evolutionary information, such as the evolutionary trace (ET) method. ET ranks the residues of a protein structure by calculating the scores for relative evolutionary importance, and locates functionally important sites by identifying spatial clusters of highly ranked residues. After ET was developed, numerous ET-like methods were subsequently reported, and many of them are in practical use, although they require certain conditions. In this mini review, we first introduce the remaining problems and the recent improvements in the methods using structural and evolutionary information. We then summarize the recent developments of the methods. Finally, we conclude by describing possible extensions of the evolution- and structure-based methods. The prediction of functional regions in a protein is an important research focus, and many methods have been developed for this purpose . One of et al. [et al. [One of the most widely used scores to consider evolutionary information is the residue conservation at a site in an MSA. The residue conservation reflects the evolutionary selection at functional sites to maintain protein function and to retain structural folds , regardlet al.  developeet al. , which det al.  predicts [et al.  also add [et al. , which iet al. [et al. [et al. [etc., and are summarized as a table (html or downloadable xlsx format). CUBE-DB presently covers only human proteins belonging to multi-member families.Zhang et al.  develope [et al.  to refer [et al.  used het [et al. , etc., aet al. [It is difficult to predict all of the types of functional regions by a single score, because each functional region has its own physico-chemical properties. For example, protein interfaces are not simply discriminated from non-interface surfaces by the patches of conserved residues . The moset al.  addresseet al. , to deteet al. [et al. [st November, 2013, the SitesIdentify server is not working at the URL described in the original paper [Teppa et al.  comparedet al. , cumulatet al. , proximiet al. , evolutiet al. , and theet al. ) to idenet al. , 24–26,  [et al.  developeal paper .et al. [et al. [et al. [et al. [The evolutionary scores calculated in an MSA used for functional region prediction are roughly divided into two types: the scores at a site and those between sites. The former type is the conservation/variation of amino acids at a site, while the latter one is the score of the degree of coevolutionary relationship between two or more sites. In our opinion, the performance comparisons by Teppa et al. , describet al. , 29, MI et al. –36, and et al. , have beet al. –38 but aet al. , regardl [et al.  investig [et al.  performe [et al.  highligh [et al. .et al. [et al. [The availability of many protein sequences enables the use of various statistical approaches to address this problem. Recently, discrimination between directly and indirectly correlated residues was achieved by the direct-coupling analysis (DCA) by Weigt et al. . DCA comet al. . In addiet al. –50. Theset al. –49. Howe [et al.  applied  [et al. , 51.etc.) can be considered simultaneously at both the nodes and edges, to highlight the information encoded within an MSA. Such a visualization tool clarifies the intricate evolutionary connections among sites.In addition, one of the recent advances in coevolution-based approaches is the development of MISTIC , by whicAlmost all annotations assigned to protein sequences rely primarily on the computational identification of similarity between the protein sequences with unknown and known functions, which are identified by BLAST  and otheet al. [http://mammoth.bcm.tmc.edu/eta/manual.Recently, Kristensen et al.  applied et al.  is descrz-score for every function is assigned to every node. The function corresponding to the most significant score is adopted at each node, as its annotation, for example, by referring to the Enzyme Commission (EC) numbers of the retrieved structures. In high throughput controls, this competitive diffusion process recovered enzyme activity annotations with 99% and 97% accuracies at half-coverage for the third and fourth levels of the EC number, respectively, although currently these predictions have only been evaluated for homologs. These accuracies corresponded to false positive rates 4-fold lower than that of the nearest-neighbor method and 5-fold lower than that of the sequence-based annotations.html. At first, a few key functional residues are clustered into 3D templates, and local structures similar to them are searched for in other protein structures. Secondly, when the 3D template is matched in the structure of a protein, the function of the structure in the found protein is transferred to the query structure. In order to increase the sensitivity of the functional annotation , the proet al. [et al. [The selection of homologous sequences is a critical step in the prediction of functional regions by using the conservation score, because conserved residues are identified through comparisons of homologous sequences . The samet al.  develope [et al. , 86 appl [et al. , 86. The [et al. . They sh [et al. . FREPS i [et al. . Structu [et al. , 86, how [et al.  and resi [et al. , 86 shouet al. developed GeMMA [We would like to conclude by describing three possible extensions of the methods using structure and evolutionary information. The first is the extension to identify the functional differences of closely related proteins. In considerable numbers of protein families, a subfamily develops a new function, changes substrate specificity, or loses an original function. These family members can be categorized into several subfamilies, for investigations of their functions. Several databases and methods have been developed. For example, the FunShift database  is a coled GeMMA , which aed GeMMA . The comed GeMMA , DSPAC wed GeMMA , 86. In ed GeMMA  could beThe second point is the extension to the template selection in homology modeling, by the application of evolutionary information. See details in our previous work . Homologet al. [The third point is the extension to protein design , which iet al.  develope


The fabrication and characterization of a radio frequency (RF) micromachined switch with annealing were presented. The structure of the RF switch consists of a membrane, coplanar waveguide (CPW) lines, and eight springs. The RF switch is manufactured using the complementary metal oxide semiconductor (CMOS) process. The switch requires a post-process to release the membrane and springs. The post-process uses a wet etching to remove the sacrificial silicon dioxide layer, and to obtain the suspended structures of the switch. In order to improve the residual stress of the switch, an annealing process is applied to the switch, and the membrane obtains an excellent flatness. The finite element method (FEM) software CoventorWare is utilized to simulate the stress and displacement of the RF switch. Experimental results show that the RF switch has an insertion loss of 0.9 dB at 35 GHz and an isolation of 21 dB at 39 GHz. The actuation voltage of the switch is 14 V. The insertion loss and isolation of the RF switch were 0.4 dB and 28.0 dB at 10 GHz, respectively. Zhu et al. [et al. [et al. [2 layer, and the CPW was made by the electroplated copper. The switch had an actuation voltage of 10 V and an isolation of 20 dB at 15 GHz. Chang et al. [et al. [et al. [et al. [et al. [et al. [et al. [Radio frequency switches are applied in wireless communication systems . Compareet al.  presenteu et al.  employed [et al.  used the [et al.  proposed [et al.  develope [et al. , Kügeler [et al. , Chang e [et al. .The commercial CMOS process has been employed to manufacture various microdevices –14. Micr2.The insertion loss and isolation of the RF switch depend on the flatness of membrane. To obtain excellent membrane flatness, this study adopts an annealing process to improve the residual stress of the membrane. The insertion loss and isolation of this work exceed that of the previous works ,21. In a3; Young's modulus, 70 GPa; Poisson's ratio, 0.3 [The FEM software CoventorWare was used to simulate the stress and displacement of the RF switch. According to the structure as shown in tio, 0.3 . Figure The simulation results reveal that the maximum stress of the RF switch is 38 MPa that locates at the anchored end of the springs. The maximum stress of the switch is below the yield strength of aluminum (124 MPa). Thereby, the deformation of the switch operates in the elastic range.The characteristic impedance of the CPW lines was evaluated using the Agilent CAD tool. The electrical properties of the RF switch are simulated using the Ansoft Q3D extractor and the Agilent ADS. The electrical parameters of the switch in accordance with the dimensions as shown in 3.The 0.35 μm CMOS process of the Taiwan Semiconductor Manufacturing Company  was employed to fabricate the RF switch. The process flow of the RF switch was illustrated in The material of springs and membrane was aluminum. The anchors were the laminated structures of aluminum and stack-via layers. The material of via layers was tungsten. A sacrificial silicon dioxide layer was located under the membrane and springs. The switch needed a post-process to etch the sacrificial silicon dioxide layer and to release the membrane and springs –25. Figu4.The membrane of the RF switch produced a deformation because of residual stress. To characterize the deformation of the membrane, a white light interferometer was used to measure the profile of the RF switch. The performances of the RF switch were measured using an Agilent 8510C network analyzer and a Cascade probe station. The S-parameters of the switch were obtained by a de-embedded procedure to remove the undesired pad parasitic . The RF The RF switch without annealing was also tested. As shown in et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [Zhu et al.  proposed [et al. , the RF  [et al.  presente [et al. , the act [et al. . The rea [et al.  develope [et al.  because  [et al.  manufact [et al. , the act [et al. . The rea [et al. .The insertion loss and isolation are two important performances of RF switches. Several methods can enhance the performances of insertion loss and isolation, such as adopting GaAs substrate or high resistivity substrate to reduce substrate loss ; reducin5.A RF micromachined switch has been fabricated using the commercial CMOS process. The switch needed only one wet etching post-process step to release the suspended membrane and springs. The advantages of the post-process were easy execution and low cost. In addition, the post-process was compatible with the commercial CMOS process, so the RF switch has the potential for mass-production. In order to reduce the influence of residual stress for the RF switch, an annealing process was adopted. The membrane of the switch obtained an excellent flatness after the annealing at 300 °C for 30 min. The simulation results showed that the pull-in voltage of the switch was about 14 V. Experiments showed that the actuation voltage of the switch was 14 V that the value was in good agreement with the simulation value. The measurement results showed that the RF switch had an insertion loss of 0.9 dB at 35 GHz and an isolation of 21 dB at 39 GHz.


Dear Editor,et al. entitled “The Effect of Biofeedback Therapy on ICIQ-SF Scores and Urodynamic Parameters in Patients with Stress Urinary Incontinence” (et al. (I read with great interest the article by Seckiner tinence” . The aut (et al.  showed t (et al.  suggeste (et al. . Other m (et al. , 6, 7. T (et al. . Results (et al. .Another aspect discussed in the article is the need for exercise continuity at home. I am in total agreement with the authors, since exercises must be continued in order to avoid the emergence or worsening of symptoms. This matter should be emphasized more in studies, and include a description of the forms of patient adherence and incentives, especially over the long term.


Pluripotent human embryonic stem cells (hESCs) are able to differentiate in all different specialized tissues . Yet, asHowever, Bogomazova et al.  now convThe work of Bogomazova et al.  hence in


The 2011 IEEE International Workshop on Genomic Signal Processing and Statistics (GENSIPS 2011) was organized in San Antonio, Texas from December 2-4th. GENSIPS'11 provided a forum for researchers in the signal processing community, other related computational experts, and biomedical scientists to exchange ideas and discuss signal processing challenges due to the high modality of disparate high-throughput data, high variability of the data acquisition, high dimensionality of data, and high complexity of genomics and proteomics systems. The theme of GENSIPS'11 was cancer and computational biology and GENSIPS featured prominent plenary speakers including Dr. John N. Weinstein from UT MD Anderson Cancer Center, Dr. Stephen Wong from Methodist Hospital at Cornell University, Dr. David Nelson from Baylor College of Medicine and Dr. Chung-I Wu from the Beijing Institute of Genomics.This supplement contains extended versions of selected articles from GENSIPS conference proceedings. Each submitted article to the conference was reviewed by a minimum of two reviewers and the top twenty favorably reviewed papers from sixty selected papers (33%) were invited to submit the extended versions for this supplement. The extended journal versions were further reviewed according to rigorous peer-review criteria.The accepted articles can be broadly categorized into four groups:et al. [et al. [α Chip-seq data from the MCF-7 cell line. Fine-scale modeling of genetic regulatory networks using stochastic master equation models entails a huge computational complexity and Karim et al. [et al. [et al. [Models of genetic regulatory networks can belong to the class of deterministic or stochastic, discrete or continuous, fine-scale or coarse-scale quantitative models. The availability of experimental data, prior biological knowledge and purpose of modeling frequently guide the selection of the quantitative model to represent the biological network. Sridharan et al.  provideset al.  consideret al. , a Boole [et al.  providesm et al.  presents [et al. , a quantet al. [et al. [For analysis of DNA methylation profiles, Zhang et al.  presentset al.  applies  [et al.  proposes [et al.  proposeset al. [et al. [Targeted cancer therapy is considered to be a cornerstone for personalized medicine. Research problems in this area include understanding and modeling the mechanisms of action of molecularly targeted drugs and design of combination drug therapies. Li et al.  presents [et al.  proposes [et al.  presentset al. [et al. [et al. [et al. [et al. [et al. [et al. [Advancement in measurement technologies provides vast quantities of experimental data on various components of the regulome. This requires new approaches for the systematic generation and analysis of the experimental data. For large-scale protein profiling, Sun et al.  provides [et al.  proposes [et al.  presents [et al.  studies  [et al.  proposes [et al.  analyzes [et al. . The appThe authors declare that they have no competing interests.All authors served as editors for the supplement, with RP serving as the Lead Editor. All authors helped write this editorial.


Acta Cryst. (2013), E69, o906–o907.Corrigendum to  et al.  is corrected.The correspondence address in the paper by Huang


Acta Cryst. (2004), E60, o2295–o2297.Corrigendum to  et al.  is corrected.The name of one of the authors in the paper by Watkin  In the paper by Watkin et al. (2004)


A biosensor is a physicochemical or hybrid physical-chemical-biological device that detects a biological molecule, organism, or process. Because of the nature of their targets, biosensors need to be faster, smaller, more sensitive, and more specific than nearly all of their physicochemical counterparts or the traditional methods that they are designed to replace. Speed is of the essence in medical diagnosis as it permits for rapid, accurate treatment and does not allow patients to be lost to follow-up. Small size and greater sensitivity mean less-invasive sampling and detection of molecules such as neurotransmitters or hormones at biologically-relevant levels. Greater specificity allows assays to be performed in complex fluids such as blood or urine without false negative or false positive results.Nanotechnology promises to improve biosensing on all of these fronts. Nanofabricated materials can bind directly to biomolecules and/or act as transducers to extremely small and sensitive detectors. Their sensing mechanisms can be sensitive at the single-molecule level, and include standard outputs such as fluorescence and color as well as label-free techniques such as evanescent wave coupling or electrochemistry.et al. [et al. [et al. [This Special Issue reviews and introduces some ways in which nanofabrication and nanomaterials can aid in specific biomolecule detection. Several of the papers present complete lab-on-chip systems for microfluidic sample delivery and analysis. Germano et al.  present  [et al.  improve  [et al.  have devet al. [et al. [2 nanospheres as a humidity sensor. Prakash et al. [Principles of microfabrication for improved sensors are discussed by Passaro et al. , who mod [et al.  present h et al.  review tet al. [et al. [et al. [Other papers evaluate the potential of novel materials, particularly nanoparticles, to serve as biosensors. Three papers in this issue discuss biosensing using fluorescent semiconductor nanoparticles (quantum dots). Orcutt et al.  contribu [et al.  provide  [et al.  have wriet al. [et al. [et al. [et al. [Not all nanoparticles show photoluminescence, but their optical properties may still be useful for biosensing. Kim et al.  show tha [et al.  review t [et al.  review e [et al.  who demoet al. [Liu et al.  review het al. [Finally, Rezek et al.  attack aThis collection gives a flavor of the many challenges faced in biosensing: functionalization, signal transduction, nonspecific interactions, and practical system integration. Many of the techniques and approaches have broad application and will be able to be adopted by multiple laboratories. Others represent complex systems that will be packaged into commercial devices that replace benchtop instruments with smaller, lighter, possibly field-ready sensors. Our hope is that the successes as well as the limitations of these sensors, and the general principles upon which they are based, can inspire further innovation in this rapidly-expanding field.


Dear Editor,I have read with interest the paper of Tayyebi et al.  and I am


Dear Editor,I read the recently published article by Adib-Hajbaghery et al.  in your


In the paper by Samineni et al. , the fol


Acta Cryst. (2010), E66, o1881.Corrigendum to  et al.  is corrected.The name of one of the authors in the paper by Hussain


Acta Cryst. (2004), E60, o909–o910.Corrigendum to  et al.  is corrected.The name of one of the authors in the paper by Newton


Dear Editor,I read with interest the article by Mogadam et al.  in which


Acta Cryst. (2011), E67, o2143.Corrigendum to  et al.  is corrected.The name of one of the authors in the paper by Kluge


The tenet of this presumption should be held dearly by all, and we as scientists should strive to reduce practices that cannot be supported. Biedermann et al.  appear t [et al.  and othe [et al. ) have di [et al.  that we  [et al.  is clearet al. [et al. stated 'it remains questionable whether scientists should interfere with a topic of which practicing legal decision makers are already well aware and that, above all, they are in a better position to appreciate' and cite the case State of New Jersey versus Spann [et al. have misunderstood the decisions in the Spann and Collins cases. These cases fully support our call for an empirical basis for assumptions and that untethered use of personal belief is not acceptable. The court is calling for more justification and guidance and that scientists not usurp the responsibility of the jury. Courts typically do not prescribe science to scientists; they demand that the scientists support their conclusions with data. Personal beliefs alone are not a sufficient basis for entering scientific evidence into legal proceedings. However, in contrast to the misunderstandings of Biedermann et al., the Courts in Collins and Spann have prescribed what is not scientifically acceptable.Budowle et al.  describeet al. , which hus Spann . Biedermet al. [Contrary to the position promoted by Biedermann et al. , we advoet al. [et al. [et al. missed these concerns when reviewing the literature.It is worth noting that Jackson et al. , of whic [et al.  to suppoThe authors declare that they have no competing interests.BB was responsible for drafting the response. JG, RC, and HG-K contributed to the response and provided edits. All authors read and approved the final reply.


These exchanges highlight the role of scrutiny in studies with potential effects on humans, but also raise questions about minimum requirements for demonstrating biological effects.Recent nuclear accidents have prompted renewed interest in the fitness consequences of low-dose radiation. Hiyama  Natural background radiation varies by more than a factor of 300 with significant negative effects on mutation, immunology and disease . Low-doset al. [Zizeeria maha under field conditions in Japan.Surprisingly, the health consequences of nuclear accidents are poorly understood . For exaet al.  presenteet al. [The paper by Hiyama et al.  has beenet al. .et al., the sample sizes, and the analyses are standard for ecological and evolutionary studies, so there is no major reason for objections. Still, numerous objections were raised to these interesting findings. In a rebuttal Hiyama et al. [The approaches adopted by Hiyama a et al.  providedBut the great strength of this study rests with the use of lab-based experimental manipulations of radiation that capture the genetic and phenotypic consequences observed in the wild-caught populations. In the absence of such experimental manipulations this study would be far less convincing given the small sample sizes of field collections, and lack of replication of populations within contaminated areas with the result that a dose–response relationship could not be characterized for wild populations. However, the use of experimental manipulations provides unambiguous support for the hypothesis that radioactive fallout is the likely cause of the abnormalities observed in the field and this effectively counters all of the major criticisms that have been levied at this study.et al. [et al. [The papers by Hiyama et al. ,10 raise [et al. ,10 to be [et al. . Given tet al. [et al. [Finally, Hiyama et al.  emphasizet al. . Hopeful [et al.  will pro


Dear Editor,et al.[We thank Jain et al. for theiet al. We do aget al.et al.[Treatment with oral steroids along with oral acyclovir is definitely justified in our case. In contrast, we do see cases of EM minor with only ocular involvement in the form of coin-shaped lesions which will definitely improve only with topical steroids just like the case described by Jain et al. As we ha


Here we present an opinion on “motor neglect,” one of the several scotomas in neglect research  is an increase of the coupling between ipsilesional premotor areas . Such coupling may be critical in patients with motor neglect. Recent studies suggest that noradrenergic (NA) stimulation may be the tool for the job. Grefkes et al. (As yet (as far as we know) there have been no studies specifically addressing rehabilitation for motor neglect. Exciting new techniques such as repetitive TMS and tDCS (used either to enhance the activity in the lesioned hemisphere or at suppressing the over-activity observed in the unaffected hemisphere) have been used for visuospatial neglect t et al.  report nt et al.  have args et al.  used a cs et al. . In addis et al.  studied s et al. . As the s et al. , NA stim


Acta Cryst. (2010), E66, m570.Corrigendum to  et al.  is corrected.The address of one of the authors in the paper by Salam


A significant clinical problem is patients presenting with exercise-limiting dyspnoea, sometimes with associatedchest pain, in the absence of detectable left ventricular (LV) systolic dysfunction, coronary artery disease, or lungdisease. Often the patients are older, female, and have isolated basal septal hypertrophy (BSH), frequently on a backgroundof mild hypertension. The topic of breathlessness in patients with clinical heart failure, but who have a normalejection fraction (HFNEF) has attracted significant controversy over the past few years. This review aims to analyse theliterature on BSH, identify the possible associations between BSH and HFNEF, and consequently explore possible pathophysiologicalmechanisms whereby clinical symptoms are experienced. In 1978, Maron et al. [Focal hypertrophy of the basal inter-ventricular septum is a well-recognized but poorly understood echocardiographic finding Fig. . In 1978et al. [et al. [et al. study. Using different definitions, later authors reported prevalence rates as high as 10% for isolated BSH [Prospective studies suggest that up to 10% of cardiovascular cohorts may have isolated BSH. Shapiro et al.  conducte [et al.  identifiated BSH , 5. Whilet al. [et al. [et al. [To date, only 3 studies have assessed the prevalence of isolated BSH in otherwise healthy individuals. Diaz et al.  evaluate [et al.  and Ayou [et al.  have cor2). Moreover, the additional load created by pressure from the right ventricle exerts additional stress on the septum. Therefore, it is conceivable that the basal septum hypertrophies earlier than other LV regions in response to increased afterload as it already operates under higher loading conditions [The precise mechanisms leading to isolated BSH have yet to be determined but plausible reasons exist as to why the basal septum might be uniquely susceptible to hypertrophy. For example, Laplace’s law states that the larger a vessel’s radius, the larger the wall tension required to withstand internal fluid pressures . Becausenditions .et al. [et al. [Irrespective of whether the basal septum is more susceptible to hypertrophy, there is evidence linking its presence to that of systemic hypertension. Verdecchia et al.  performeet al.  corrobor [et al.  demonstr [et al.  stronglyet al. [et al. [Objective evidence for the heightened susceptibility of the basal septum to the structural and functional alterations triggered by hypertension was provided by Baltabaeva et al. . Using set al. . Additio [et al.  observedAs an anatomical component of the left ventricular outflow tract (LVOT), a hypertrophied basal septum could alter systolic haemodynamics in a manner akin to the ‘septal bulge’ in HCM that is associated with dynamic LVOT obstruction in the presence of systolic anterior motion (SAM) of the mitral valve . Dynamicet al. [et al., DSE itself is not physiological exercise. Indeed, Luria et al. [Henein et al. , 22 testa et al. , found tet al. [-1 on DSE. After treatment with atenolol , repeat DSE showed a marked reduction in LVOT velocities  and breathlessness  in the 11 patients who tolerated beta-blockade Ranasinghe et al. [Al-Nasser et al.  subsequee et al.  substantet al. [3).Whilst it is unlikely that a focal anomaly such as BSH could increase LV passive stiffness in the absence of global hypertrophy, abnormal septal motion due to BSH could hinder energetic myocardial relaxation [et al. [Optimal LV diastolic filling is dependent on an active early untwisting process (relaxation) and on the intrinsic passive characteristics (compliance) of the ventricle. Kitzman et al.  have prolaxation , 27 and  [et al. , 22, diaet al. [Tissue Doppler Imaging (TDI) provides reliable non-invasive measurement of LV relaxation  and its et al.  found thet al. attempted to disentangle the relative contributions of systolic (via LVOT obstruction) and diastolic dysfunction to the genesis of dyspnoea during DSE in BSH patients [ et al. [-1 at peak stress with associated dyspnoea. Unlike Henein et al., the E/A ratio did not change. In a follow-up study using TDI [Yalҫin patients , 32. At [ et al. , LVOT ve et al. [et al. [ et al. [Research on BSH is limited by the variation in criteria used to diagnose it. For example, Henein et al.  used a m [et al. , 32 adop[ et al.  used a pet al. [The inconsistency in our approach to diastolic dysfunction particularly hinders proper appraisal of the mechanism(s) via which BSH could trigger symptoms. An editorial by Henein et al.  outlineset al. . Yet, noAccumulating evidence suggests that β-blockade is effective in reducing LVOT velocities and breathlessness in patients with BSH during DSE and exercise , 24, and


Dear Editor,We read carefully the article by Zehedi et al.,  which de


Dear Editor,et al.[I read with interest the article by Shetty et al. on the set al. in additet al.–5


Acta Cryst. (2012), E68, o1366.Corrigendum to  et al.  are corrected.The title and Scheme in the paper by Wang


Over the past half century the molecular underpinnings of the variability in human cancers has been gradually revealed but within the last 5 years there has been an explosion in our ability to determine and learn from cancer heterogeneity, through the use of next-generation sequencing and related methods. The complexity and variation in the structure of cancers can seem daunting, but important lessons in cancer biology and the approaches to therapy can be learned from studying how much of the complexity is subject to change and how much is a consequence of stochastic rather than deterministic processes. The evolution of clones, individual variation in response to therapy, distinct biological subtypes of cancer and tumor immune responses are all examples of the heterogeneous nature of human cancers. Self evidently, when heterogeneity is used to describe any aspect of a cancer, it is important to know which variational feature is being addressed.The term heterogeneity covers many aspects of the variability in tumor phenotypes, which are a characteristic of human malignancies. Morphologists of the late 19et al. [et al. [et al. [et al. [et al. [A review by Hiley et al.  sets the [et al. ) and, by [et al. , Nadauld [et al. ). These  [et al.  provideset al. [et al. [et al. [Of equal importance to the experimental approaches used to study heterogeneity are the methods used to evaluate heterogeneity across the spectrum of variation that can be measured in cancer by different assay types. These encompass next-generation sequencing methods for analyzing tumor and normal cell composition, the analysis of clonal populations in cancers , and me [et al. ). Hence, [et al.  advocateResolving structure and function with single cell approaches is also becoming important, both in studies of clonality as well as for functional assessment of tumor cell populations. Learning how to reconcile whole tumor cell-based population approaches with the single cell data will be important. Nicholas Navin’s review  of singlet al. [et al. [et al. [et al. [et al. [et al. [Next-generation sequencing-based studies of RNA populations from cancer cells are revealing important aspects of transcriptional activity and its role in cancer. A review by Patrick Nana-Sinkam and Carlo Croce  sets theet al.  present  [et al.  describe [et al.  will als [et al.  , Fleisc [et al. , and Cha [et al. ).et al. [As our underlying knowledge about cancer genomics and heterogeneity improves, the need to translate this information into informed cancer care for patients is an obvious next step. Berger and Varghese have contributed an Opinion piece  to descret al. , delineaet al. [Finally, in the genomic era, sharing of data and complete descriptions of analytic methods, to the level of providing code in addition to data, will prove crucial to continued success. Boutros et al.  provide et al.  present


Acta Cryst. (2014), E70, o624.Corrigendum to  et al.  is corrected.The affiliation address of one of the authors in the paper by Chicha


Hemminki et al.  estimate [et al.  of an Am [et al.  of a conet al. [et al. [P = 0.023). Obesity was not studied per se.Associations between obesity and RA development have now also been studied in patients at high risk for progression to RA. van der Helm-van Mil et al.  investig [et al.  found beThese findings highlight the importance of a better understanding of the factors contributing to RA development, in particular any modifiable risk factors that we might address to reduce risk in various populations. We feel there is a signal that obesity is an important contributor to RA risk, but that further study is still merited.


Dear Editor:Mycobacterium avium subspecies paratuberculosis (MAP) infection. Opportunely, a prospective study  may be consequent to a  Kalfus,  is addreet al.,et al.,et al.,et al.,MAP is inhibited by agents that the scientific community categorizes as anti-inflammatory (Greenstein et al.,et al.,et al.,et al.,et al.,et al.,et al.,Disconcertingly, the inclusion criteria in the ongoing study Kalfus,  are esseet al.,et al.,et al.,et al.,We suggest that calling the study now recruiting Kalfus,  “placeboA consistently flawed study design may yet again be misinterpreted as showing no added efficacy of anti-MAP agents in CD. Consequently, the potential identification of the etiology of IBD as being due to the zoonosis of MAP may irrevocably be lost.


We read with interest the study by Vural et al. , who aim


In Table 1, the location for Waterhouse PJ et al. (2008) is incorrect. Please see the corrected


In the right hemisphere (RH) they observed RS in both high and low repetition-probability blocks and, importantly, the magnitude of this RS was similar between the blocks. Thus their RH LO data fully agrees with that of the Kovács et al.  the LH in the Mayrhauser et al. (What then could have caused the discrepancy between the studies? Mayrhauser et al.  observeds et al.  paper [ps et al.  when coms et al.  study fos et al.  did not s et al. . In facts et al.  and Grots et al.  data sugs Figure . This sur et al.  study isrep effects observed in some studies (Figures Figure  Figures , which c Figures  appears  Figures . DefininThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Addiction, for which Professor Babor was Associate Editor-in-Chief. This provides context to faulty comments made by Xuan et al.  causal inference is limited” It comes as a surprise that Xuan et al.  seek addXuan et al.  could ha


Brain and Language, 2005, 94, 72-85) reported evidence for significant improvements in phonological awareness in mainstream children following 6 h of exposure to a commercially available phoneme discrimination training programme, but not in a control group. In a follow-up study, we failed to replicate this finding, despite using an almost identical training programme . This paper directly compares the methods and the results of the two studies, in an effort to explain the discrepant findings. It reports that the trained group in Moore et al. (2005) showed significantly greater improvements in phonological awareness following training than the trained group in Halliday et al. (2012). However, the control group in Halliday et al. (2012) showed significantly greater improvements in phonological awareness than the control group in Moore et al. (2005). The paper concludes that differences in the randomization, blinding, experimenter familiarity and treatment of trained and control groups contributed to the different outcomes of the two studies. The results indicate that a plethora of factors can contribute to training effects and highlight the importance of well-designed randomized controlled trials in assessing the efficacy of a given intervention. © 2014 The Authors. Dyslexia published by John Wiley & Sons, Ltd.In a previous article, Moore, Rosenberg and Coleman ( With the advent of learning technologies, the fledgling field of ‘educational neuroscience’ is fast becoming a cornerstone of educational policy and practice. Educators are encouraged to follow an evidence-based approach, seeking out intervention studies with a view to informing practice. However, with an explosion of research papers published in the last decade, the task of interpreting that research is no mean feat  arise from a low-level deficit in processing auditory information  SLI  training programme . Phonomena was a computer-based auditory training programme designed to train the discrimination of English phonemes in order to accelerate language learning in multiple target groups . The parent company, MindWeavers Ltd, has since ceased trading. In Moore et al. (n = 12) but did not receive any training (‘NI’ control group). Immediately before (pre-training) and after (post-training) training, both groups were given a battery of standardized tests of phonological awareness ; Frederickson, Frith, & Reason, et al. . A second group was trained on an auditory frequency discrimination task designed to match the PD task in terms of task demands , and a third group was trained on a visual analogue of the AFD task, a visual frequency discrimination task . Finally, a fourth group of children received no intervention and participated in normal school activities during training . As in the Moore et al.  and the two NI groups  from Moore et al.  and Hall . Consequently, for the Alliteration subtest only, data were analysed using nonparametric statistics.Participant characteristics for the two studies are shown in Table et al.  = −2.96, p = 0.005.Differences in the amount of training received by the two trained groups are also shown in Table et al.  study  = 76.05, p < 0.001 , and F = 23.28, p < 0.001 , respectively.Figure et al.  study, fet al.  = 0.93, p = 0.341 , or Spoonerisms subtests, F = 0.05, p = 0.829  after controlling for pre-training scores.Figure et al. . The PD-et al.  = 6.62, p = 0.014 , and the Spoonerisms subtests, F = 6.83, p = 0.013 , after controlling for pre-training scores.Pre-training to post-training change following training for the PD groups from the studies of Moore et al.  and Hall  = 13.85, p = 0.001 , and Spoonerisms subtests, F = 17.07, p < 0.001 , after controlling for pre-training scores.The change in pre-training to post-training scores is compared in Figure et al.  and Hall , the analyses were repeated after excluding these children. The results remained the same throughout .et al. (et al. (et al. (et al. (The analyses reported in the previous texts directly compared the methods and results of the studies of Moore et al.  and Hall (et al.  in an ef (et al.  showed s (et al.  did not.et al. (et al. (et al. (et al. (A comparison of the participant characteristics of the two studies indicates that it is unlikely that these differences contributed to the discrepant findings. First, the proportions of nonnative English speakers in each of the two studies did not differ significantly, but even when these children were excluded from the analyses, the results remained the same. Second, children in the study of Halliday et al.  were sli (et al. . However (et al.  compared (et al. , particuet al. (et al. (et al. (et al. (less learning on the PD task. Nevertheless, there is some suggestion that a variable presentation paradigm can yield greater generalization of learning than a fixed presentation paradigm, at least in some listeners (Amitay, Hawkey, & Moore, et al. (Differences in the training methods of the two studies also cannot entirely account for the results. Although the two studies used different training procedures, the 3-interval, 2-alternative forced-choice AXB paradigm used by Moore et al.  has been (et al.  (Amitay, (et al. . Neverth (et al.  for thei (et al.  may have (et al. . However, et al.  will havet al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (A more parsimonious explanation is that differences in the designs of the two studies were largely responsible for our failure to replicate the results of Moore et al. . There w (et al.  and Hall (et al. . First,  (et al.  were ass (et al. . Second, (et al.  had a NI (et al.  also inc (et al.  were bli (et al.  were not (et al.  were bli (et al.  were not (et al. , all gro (et al. . Finally (et al.  were onl (et al.  had reguet al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (et al. (How can these design features account for the differences in the findings between these two studies? First, it is possible that the results of the study of Moore et al.  were sub (et al. , it was  (et al. , childre (et al. , childre (et al.  were sub (et al. . This wo (et al.  were not (et al.  did not  (et al. . This woet al. (The implications for these findings are twofold. First, the results of Halliday et al.  suggest et al. (et al. (et al. (Finally, it is important to note that the findings reported here in no way challenge the efficacy of the Phonomena programme in accelerating language learning in children. Halliday et al.  used onl (et al. , Moore e (et al.  also use


In Response: Regarding the comments by Berry et al. .


Although this factor may explain some gene absences from genomic assemblies, we believe it is insufficient to account for the extensive syntenic losses described in Lovell et al.Hron www.dx.doi.org/10.1186/s13059-015-0724-zPlease see related article:  We cons [et al.  report a [et al. ) that we [et al. ) by cond [et al.  do not c [et al.  “can be  [et al.  do align [et al. ). Thus, et al. [et al. [The main set of 274 missing genes we reported  represenet al. [The report by Hron et al.  has conset al. . Given t