Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
fitz  hugh  curtis syndrome is an extra - pelvic manifestation of pelvic inflammatory disease ( pid ) and is characterized by perihepatic adhesions between liver capsule and diaphragm or anterior peritoneal surface(13 ) .
most fitz  hugh  curtis syndrome patients are women of child bearing age and rarely has the syndrome been reported in males .
the predominant symptom is pain in the right upper quadrant , which may be confused with biliary disease
an abdominal computed tomography ( ct ) scan may reveal subcapsular enhancement of the liver in arterial phase ( 4 ) . we herein report a case of fitz  hugh  curtis syndrome in a male patient that was diagnosed via laparoscopy .
a 29 year - old african american male with russel - silver dwarfism presented with one day history of diarrhea , nausea , vomiting , right side abdominal pain , and abdominal distention .
the pain was constant , gradually increasing in severity , and not related to food intake .
his medical history was significant for russel - silver dwarfism , calcium deficiency , cardiomegaly , and bilateral testicular implants for undescended testicles .
the patient was sexually active only with his girlfriend and denied any history of sexually transmitted disease . on examination patient was afebrile and his vitals were stable .
laboratory workup revealed white blood cell ( wbc ) count of 14,000/l with normal liver function tests .
ct scan of the abdomen and pelvis showed a small amount of free fluid in pelvis ; the proximal appendix appeared normal , however the distal appendix was not visualized .
the liver capsule appeared normal and there was no subcapsular fluid collection ( figure 1 ) .
ct scan showing normal appearing liver capsule and no perihepatic fluid collection the patient was admitted to the surgical service .
he was made nil per os ( npo ) , and placed on intravenous fluids and pain medication .
he was refusing any surgical intervention at this point . on hospital day 5 , a repeat abdominal ct scan demonstrated a normal appearing liver , small bowel , large bowel , and appendix , with a mild increase in pelvic free fluid .
as the patient 's symptoms did not improve with conservative management , he ultimately agreed to undergo a diagnostic laparoscopy , and was taken to the operating room on hospital day 9 .
the small bowel was run in a retrograde fashion starting at the caecum , and no stricture , mass , or perforation was noticed .
appendectomy was not performed as per patient'swishes . following the procedure , the patient reported complete resolution of his symptoms .
his diet was gradually advanced , which he tolerated well , and was discharged on post operative day 2 .
fitz -hugh  curtis syndrome was first described in 1920 by carlos stajano . in the 1930 's thomas fitz
hugh and arthur curtis also described the syndrome and made a connection between right upper quadrant pain following a pelvic infection and violin  string like perihepatic adhesions(5 ) . the first case of gonococcal perihepatitis in a male
the incidence ranges from 4% to 14% in women with pid , but is as high as 27% in adolescents with pid , whose less mature genitourinary tract anatomy makes them more susceptible to infection(1 ) .
the inflammation of the liver capsule has been attributed to the direct bacterial spread from an infected fallopian tube via the right paracolic gutter . in men , hematogenous and lymphatic spread to liver
the predominant symptoms are right upper quadrant pain , tenderness , and pleuritic right sided chest pain(2 ) .
these symptoms can pose diagnostic challenges as they may be confused with biliary tract symptoms . in a clinical setting ,
the diagnosis is adequately established by excluding other possible causes of right upper quadrant pain . on laboratory examination ,
white blood cell count can be elevated in nearly half of the patients , while liver function tests are normal in most patients . because urethral cultures frequently fail to demonstrate the presence of gonorrhea and chlamydia , the serologic microimmunofluorescence antibody test is helpful in diagnosis ( 2 ) .
ct scan may show subcapsular fluid collection , thickening of hepatic capsule in the arterial phase , and wedging enhancement of the involved liver parenchyma in more than 50% of patients .
most cases of fitz  hugh  curtis syndrome are managed with antibiotics against gonorrhea and chlamydia .
it occurs mostly in premenopausal women , however , cases in males have also been reported .

Answer:
fitz  hugh  curtis syndrome is a condition characterized by inflammation of the liver capsule with concomitant pelvic inflammation without involvement of liver parenchyma .
 it is classically seen in young women who present with sharp , pleuritic right upper quadrant pain , usually but not always accompanied by symptoms of pelvic inflammatory disease ( pid ) and is frequently confused with biliary tract disease . rarely the syndrome has been reported in males , hematogenous and lymphatic spread to liver is thought to be the underlying mechanism .
 serological tests and computed tomography ( ct ) scan may aid in diagnosis of fitz  hugh  curtis syndrome .
 definitive diagnosis is made by laparoscopy , which provides both diagnostic and therapeutic benefits .
 we report a case of fitz  hugh  curtis syndrome in a young male patient , which was diagnosed and treated by laparoscopy .
 we also include a review of the literature .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
psychobehavioral approaches attempt to identify the underlying cognitive dissonance creating the intense emotional discomfort that can trigger seizures .
a recent review of psychobehavioral therapy for epilepsy recommends case reports as a research design to explore specific psychological mediators of seizure self - control .
this case report illustrates how a psychobehavioral intervention addresses cognitive dissonance in order to decrease internal stressors of seizures and was prepared according to the consensus - based care guidelines for standardized clinical case reporting .
his magnetic resonance imaging ( mri ) shows extensive bilateral gray matter band heterotopia ( fig .  1 ) .
electroclinical day- and nighttime seizures captured during video - eeg studies displayed seizures with loss of consciousness consisting of irregular shaking of his body correlating with epileptiform activity originating from bilateral parasaggital regions synchronously and tonic posturing of arms originating from the left hemisphere . before losing consciousness , he feels a loss of sensation in some of his body parts , usually starting from his right arm .
these findings suggest localization - related epilepsy originating from the left hemisphere and bilateral parasagittal regions with simple and complex partial as well as secondarily generalized seizures .
he experiences predominantly nocturnal seizures that occur in clusters of up to four complex partial seizures once or twice per week and daytime seizures once or twice per month .
a. 's parents had installed an acoustic monitoring device in his bedroom and reported that this baseline seizure frequency had remained unchanged for >  3  years prior to the beginning of the intervention .
a. is currently taking valproate , topiramate , and lamotrigine and complies with the modified atkins diet protocol .
past medication failures have included carbamazepine , levetiracetam , clobazam , and oxcarbazepine . during previous psychological assessments
, he has been diagnosed with a verbal and auditory learning disability as well as expressive language impairment . because of parental worries that challenges would increase a. 's seizure frequency , a. received parental support for doing his schoolwork , and he was never expected to contribute to household chores . as a result
, a. was deprived of opportunities to build his confidence in his own achievements and pictures himself as  broken
otherwise , a. is in good health ; he has never used alcohol or tobacco .
a. and his parents consented to the use of these data for this case report .
to resolve the resultant conflict between insecurity with his performance , fear of failure , and high expectations of himself , a. actively avoided responsibility and demanded help rather than engaging in self - reliant problem - solving behaviors .
this defense mechanism that incorporated learned helplessness and secondary gain issues was exacerbated by an anticipated challenge at school or social anxiety .
after an initial assessment period comprising two sessions of 3  h each , a treatment plan was formulated including the workbook  taking control of your epilepsy  , daily journaling , and daily relaxation exercises .
the participant received training in abdominal breathing and visualization techniques ( imaginary journey and an attention - focusing exercise ) to address early seizure warning symptoms .
the initial assessment was followed by weekly counseling sessions of 1030  min that were conducted over the phone for 12  months , and monthly sessions were conducted for a 6-month follow - up period .
a. engaged in a daily guided relaxation practice after returning from school and listened to a nonguided relaxation tape before going to bed .
he reports that he is able to interrupt warning signs of the early onset of a seizure by utilizing deep diaphragmatic breathing , visualization techniques , and self - affirmation statements of personal choice ( e.g. ,  peace and release  ) .
a. 's parents report that he took on responsibility for the completion of his schoolwork and studies in a self - motivated and timely fashion , all of which helped him to prevent the buildup of anxiety . after a nighttime seizure
, he can reliably identify the behavioral strategy which he could have employed in order to avoid the buildup of distress during the day prior to the seizure .
a. admitted that it was , at times , easier to have a seizure rather than to address the situational accumulation of seizure triggers by taking responsibility and implementing the appropriate proactive behaviors .
hence , motivational exercises were employed to allow a. to deliberately weigh the motivational factors and obstacles regarding prior set goals ( e.g. , an early bed rest ) to facilitate informed changes of his present decision - making habits . while he considered himself  broken  at the beginning of the intervention , he has developed a perspective on life in which he feels that he can shape his future according to his preferences if he follows through with taking responsibility for the acquisition of self - organizational skills ( see patient perspective in table  1 ) . by the end of the follow - up period
his nighttime seizures dropped to 12 clusters per month after 6  months of participating in the intervention .
since the internalization of the therapeutic principles is an active process that requires continuous learning , motivation , and compliance of the individual , effects are usually expected 36  months after the beginning of the intervention , especially since it takes an individual at least 12  weeks to finish the 12 sessions of the workbook .
this seizure frequency has remained stable during the remaining 6  months of the intervention and the 6-month follow - up period ( fig .
( 3  months after the follow - up period ) , the seizure frequency has still remained the same despite increasing stressors that arise within the framework of a. 's successful admission to college .
the implementation of the therapeutic strategies correlated with a cessation of daytime seizures and a clinically significant drop of nighttime seizures .
literature suggests that seizure frequency may be positively influenced by the restoration of balance within the autonomic nervous system by the regular practice of relaxation exercises and proactive avoidance of emotional distress during wakefulness , thereby preventing the buildup of seizure activity  .
furthermore , a. would regularly wake up during the night when preictal or early ictal phenomena arose ; he would then react with the application of previously practiced countermeasures .
literature indicates that evidence for the enhancement of psychological well - being by psychobehavioral therapy is more established , while reliable evidence on its role on seizure control is scarce .
the a / r intervention may represent the most comprehensively developed cognitive  behavioral approach to epilepsy   that has repeatedly been correlated with a reduction of seizure frequency in individuals with complex partial seizure disorders in uncontrolled prospective and retrospective studies , , .
the possibility of false negative self - reports of seizure occurrence can not be ruled out but seems unlikely because the patient and his parents have been very conscientious in keeping a seizure diary for a long time .
because of the uncontrolled nature of a case report , nonspecific effects of attention and natural fluctuations of seizure frequency that could have contributed to improve seizure frequency can not be factored into the interpretation of the presented data .
however , the long and stable seizure frequency prior to the intervention makes natural fluctuations unlikely .
furthermore , the decreased seizure frequency has remained stable during follow - up and post follow - up with decreased and no contact with the a / r counselor which makes unspecific effects of attention implausible .
in this case of a 16-year - old male , the acquisition of self - organizational skills and the development of seizure interruption techniques correlated with a clinically significant drop of seizures and an increased sense of  being in control  of his seizures . the case exemplifies that motivational strategies may be applied to facilitate the regulation of lifestyle - related seizure precipitants .
future prospective studies are needed to further investigate the psychological mediators of an individual 's increasing sense of seizure self - control and its actual relationship with seizure frequency .

Answer:
a recent review of psychobehavioral therapy for epilepsy recommends case reports as a research design to explore specific psychological mediators of psychobehavioral interventions for epilepsy that address the bidirectional relationship between psychological states and seizures .
 the report was prepared according to the consensus - based care guidelines for standardized clinical case reporting.this is a case of a 16-year - old male individual with a diagnosed seizure disorder and learning disability who continued to have daytime and nighttime seizures on a regular basis despite exhausting of available conventional treatment options .
 a psychological assessment led to the working hypothesis that cognitive dissonance between fear of failure and high expectations of self had led to a  broken  self - image and active avoidance of responsibility that resulted in intense emotional distress which correlated with the occurrence of seizures .
 this working hypothesis resulted in a treatment plan that employed the acquisition of self - organizational skills and relaxation techniques as the main therapeutic strategy .
 motivational strategies were employed to facilitate the regulation of lifestyle - related seizure precipitants . in this case , the acquisition of self - organizational skills and the development of seizure interruption techniques correlated with a clinically significant decrease of seizures .
 methodological limitations of the interpretation of the presented data are discussed .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
a 9-month - old , 10-kg girl without any relevant medical history was presented at our emergency room because she had aspirated a peanut 5 hours previously .
chest computed tomography showed a foreign body at the carina and the proximal right main bronchus , and emphysema in both lung fields ( fig .
anesthesia was induced intravenously with thiopental 60 mg and rocuronium 6 mg after administering atropine 0.2 mg .
approximately 25 minutes after the start of the operation , spo2 gradually decreased to 78% from 100% .
accordingly , the surgeon was asked to stop the procedure , and an uncuffed endotracheal tube ( i d 4.0 , euromedical , denmark ) was intubated and fixed at 10 cm .
left lung sounds were heard clearly , but no right lung sounds were evident on auscultation .
spo2 did not improve despite manual ventilation with 100% o2 and an increased inspiratory pressure airway was detected .
accordingly , a simple chest radiograph was taken . while waiting for the result of the chest radiograph , the otolaryngologist extubated the endotracheal tube and attempted to re - insert the rigid bronchoscope in order to check for possible causes of the airway obstruction , such as , residual foreign body .
meanwhile , the heart rate decreased to 50 beats / min , and spo2 decreased to 57% ( blood pressure was not measured ) .
atropine 0.2 mg and epinephrine 1 g were injected intravenously , but vital signs did not improve and no carotid artery pulse was palpable . external cardiac compression was performed and epinephrine 10 g was injected intravenously three times .
heart rate and blood pressure then recovered , and thus , cardiac compression was stopped .
a chest tube was immediately inserted into the right thorax and a massive air leak was observed . at this time
, the sounds of both lungs were clearly heard and spo2 improved to 100% . follow up chest radiography showed a significant reduction of the right tension pneumothorax and a scattering of subcutaneous emphysema at the left upper chest and around the neck ( fig .
the tension pneumothorax suggested major tracheobronchial injury and a subsequent bronchoscopic examination revealed three major sites of laceration , one in the mid trachea of length 1.5 cm , a second in the distal trachea of length 2 cm ( immediately above the carina ) ( fig .
4 ) , and a third in the right main bronchus of length 1 cm .
an arterial line was placed in the left radial artery to monitor blood pressure continuously .
arterial blood gas analysis showed ; ph 7.10 , paco2 63 mmhg , pao2 77 mmhg , hco3 19.6
mmol / l at fio2 1.0 , etco2 24 mmhg , and spo2 100% . after a rigid bronchoscope examination confirmed the absence of remaining foreign body , an uncuffed i d 4.5 endotracheal tube was inserted into the left main bronchus for single lung ventilation under fiberoptic bronchoscopic guidance .
however , the patient did not tolerate single lung ventilation well and her spo2 decreased to 79% . in view of the facilitation of surgical approach and the risks of hypoxemia and hypoventilation ,
after 1,000 units of heparin was injected as a bolus , a 10 fr catheter ( fem - flex ii femoral cannula , edwards lifesciences , irvine , ca , usa ) was placed in the right internal jugular vein for drainage , and a 12 fr catheter was placed in the right femoral vein for perfusion using a sono - guided seldinger technique ( fig . 5 ) .
ecmo flow was maintained at 0.7 - 0.8 l / min , and spo2 remained at 98 - 100% without mechanical ventilation . at the initiation of ecmo ,
anesthesia was maintained with continuous intravenous infusions of sufentanil 5 g / kg / h , midazolam 0.1 mg / kg / h , and vecuronium 0.1 mg / kg / h during ecmo .
dopamine was infused at 5 g / kg / min and vital signs were stabilized . an activated clotting time ( act ) of approximately 200 seconds
was maintained and arterial blood gas analysis under maximal ecmo support showed ; ph 7.34 , paco2 41 mmhg , pao2 81 mmhg , and hco3 22.1 mmol / l at fio2 1.0 .
when the ecmo flow rate reduced , it was recovered by pulling the cannula in the internal jugular vein slightly .
body temperature , measured using an oral thermometer , fell to as low as 35.0 after ecmo was initiated , and thus , a forced air warmer was applied to prevent further hypothermia .
total anesthesia time was 8 hr 25 min , estimated blood loss was 300 ml , and urine output was 120 ml ; 250 ml of crystalloid solution and 1 unit of packed red blood cells were administered .
ecmo was maintained postoperatively to minimize airway pressure . in the intensive care unit ( icu )
, the mechanical ventilation was performed using pressure control mode ( inspiratory airway pressure 10 cmh2o , pressure support 11 cmh2o , respiratory rate 20/min , fio2 0.5 and peep 3 cmh2o ) , which resulted in the expiratory tidal volume of 49 ml .
vital signs were stable in the icu , and the patient awoke with no signs of respiratory or neurologic deficit on the first postoperative day .
the simple chest radiograph taken in the icu showed reduced subcutaneous emphysema and no residual pneumothorax .
ventilating bronchoscopy has the risk of severe complications , such as , infection , laryngeal edema , laryngospasm , bronchospasm , bleeding , hypoxia , pneumomediastinum , and pneumothorax .
rothmann and boeckman   reported that the probability of pneumothorax during rigid bronchoscopy for the removal of a foreign body is approximately 1% .
therefore , the possibility of pneumothorax should be suspected when ventilation worsens during ventilating bronchoscopy . however , an early diagnosis of pneumothorax during anesthesia is not easy because the symptom is masked by anesthesia .
tension pneumothorax during surgery may manifest as a reduction in oxygen saturation , a rapid increase in airway pressure , hypotension , and/or tachycardia . in this case ,
the reasons for the delayed diagnosis in the present case were that the reduction in oxygen saturation and the diminished right lung sounds were mistakenly attributed to airway obstruction by a foreign body .
in addition , if lung sounds had been checked more carefully , it might have been easier to determine whether the respiratory failure was due to foreign body obstruction or tension pneumothorax .
furthermore , it would have been safer to evaluate airway with a fiberoptic bronchoscope inserted through the endotracheal tube under ventilation rather than attempt airway assessment using a ventilating bronchoscope after extubation . during surgery on the trachea and bronchus , a double lumen endotracheal tube or
however , in small children , because conventional single lung ventilation methods are likely to fail to maintain adequate ventilation and oxygenation , the elective application of ecmo may be a good option .
ecmo was also useful during the postoperative course in the described case because it can minimize inspiratory airway pressure during mechanical ventilation . during ecmo
, heparin was administered as a single bolus of 100 unit / kg followed by continuous intravenous infusion at 20 - 60 unit / kg / min .
anticoagulation was accomplished by titrating heparin administration to maintain an act of between 180 and 220 seconds .
furthermore , levels of blood anticoagulation were monitored hourly , and the amount of heparin administered was carefully controlled to prevent bleeding complications .
in addition , because the ecmo machine was not equipped with a sevoflurane vaporizer and almost no mechanical ventilation was performed during ecmo , intravenous opioids and midazolam were added for anesthesia .
summarizing , the tension pneumothorax should be considered when inspiratory pressure is increased and oxygen saturation is decreased during ventilating bronchoscopy .
effective communication between the operator and anesthesiologist is essential when unexpected complications are encountered to facilitate the prompt planning of coping strategies .

Answer:
tension pneumothorax during ventilating bronchoscopy for foreign body removal is a rare but life - threatening complication .
 the authors present a case of cardiac arrest caused by tension pneumothorax in a 9-month - old girl who underwent ventilating bronchoscopy for foreign body ( peanut ) removal .
 tension pneumothorax was due to tracheobronchial lacerations caused by a bronchoscope .
 the patient was successfully resuscitated by cardiopulmonary resuscitation and chest tube insertion .
 the airway injury was effectively repaired by thoracotomy under extracorporeal membrane oxygenation .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
during october 2009october 2010 , a total of 448 respiratory specimens were obtained from 448 patients ( 258 male patients and 190 female patients ) with rtis and fevers in a virus surveillance system in osaka , japan ( 9 ) . the mean  sd age of the patients was 41.4  53.7 months ( range < 1404 months ) , and 351 ( 78.3% ) were < 5 years of age .
procedures for viral nucleic acid extraction and cdna synthesis have been reported ( 9 ) .
pcr for detecting hrv and enterovirus was conducted by using evp4 and ol68 - 1 primers , which detected hrv and human enterovirus , respectively , in amplicons of 530 and 650 bp , respectively ( 7 ) .
results showed 178 positive specimens ( 140 for hrv , 16 for human enterovirus , 7 for hrv and human enterovirus , and 15 for an unexpected amplicon of 600 bp ) . to identify the 600-bp amplicon , we sequenced viral protein 4 ( vp4 ) and vp1 genes .
blast analysis ( www.ncbi.nlm.nih.gov/ ) showed that these isolates had high identity with ev68 vp4 ( 98.5%99.5% with the pav25426868 strain [ genbank accession no
. hm370293 ] ) and vp1 ( 96.7%97.5% with the md021 strain [ genbank accession no
phylogenetic analysis using vp1 sequences ( 14 of 15 osaka strains were sequenced ) demonstrated that osaka strains were clustered in 1 group and differed from previously reported strains ( figure 2 ) .
monthly distribution of enterovirus 68 ( ev68 ) in osaka , japan , october 2009october 2010 , bars indicate no .
phylogenetic tree of enterovirus 68 viral protein 1 gene sequences constructed by using a 927-nt sequence corresponding to nt sequence 23553281 in strain 3799 , osaka , japan , october 2009october 2010 .
genbank accession numbers for strains used in this analysis were fermon , ay426531 ; 3799 , ef107098 ; jpoc10200 , ab601872 ; jpoc10290 , ab601882 ; jpoc10373 , ab601873 ; jpoc10378 , ab601883 ; jpoc10396 , ab601884 ; jpoc10402 , ab601874 ; jpoc10404 , ab601885 ; jpoc10412 , ab601875 ; jpoc10441 , ab601876 ; jpoc10445 , ab601877 ; jpoc10471 , ab601878 ; jpoc10573 , ab601879 ; jpoc10616 , ab601880 ; jpoc10618 , ab601881 ; md021 , ay426491 ; tx021 , ay426495 ; mo00 , ay426493 ; wi00 , ay426494 ; mn98 , ay426497 ; tx99 , ay426498 ; md99 , ay426499 ; tx03 , ay426500 ; mn89 , ay426489 ; ny93 , ay426490 ; ev70 , d00820 ; and ev94 , dq916376
nucleotide and amino acid identities among 4 osaka ev68 ( jpoc10 - 290 , 378 , 396 , and 404 strains ; nt 5017265 corresponding to the 3799 strain ) , fermon , and 3799 strains were determined . to determine sequences , we synthesized cdna by using specific primers and amplified 4 segments ( nt 1601153 , 5433391 , 31324032 , and 37477333 corresponding to the 3799 strain ) .
the fermon and 3799 strains are the only ev68 strains for which complete genome sequences are available .
the 3799 strain was isolated from a 6-year - old girl with pneumonia in 1998 ( h. norder , pers .
the sequenced region coded partial 5 untranslated regions ( utrs ) and all structural and nonstructural viral proteins ( vp43d ) .
identities between strains were calculated by using bioedit version 7.09 ( www.mbio.ncsu.edu/bioedit/bioedit.html ) ( table 2 ) . *
osaka strains , jpoc10 - 290 , jpoc10 - 378 , jpoc10 - 396 , and jpoc10 - 404 ; vp , viral protein . among osaka strains ,
nucleotide and amino acid sequences were highly conserved ( nt identity 96.5%100% and aa identity 98.6%100% ) .
in contrast , osaka strains had lower similarities with the fermon strain ( nt identity 83.5%91.7% and aa identity 90.6%100% ) than with the 3799 strain ( nt identity 91.9%98.4% and aa identity 95.4%100% ) . when we compared individual viral proteins in osaka strains with those in the fermon strain , no gene except for vp4 showed > 90% nt sequence identity ; gene 2b showed the lowest identity ( 83.5%85.8% ) .
regarding amino acids , < 95% identity was observed in vp1 , vp2 , and vp3 in the fermon strain , and no genes with < 95% aa identity were found in the 3799 strain in contrast with osaka strains .
moreover , no integration or deletion of nucleotides was observed in vp43d sequences among osaka , fermon , and 3799 strains . to clarify why ev68 osaka strain genomes were smaller than those of other enteroviruses and the ev68 fermon strain ( 7 ) , we aligned the partial 5 utr sequences ( nt 541820 corresponding to the fermon strain ) of 4 osaka , fermon , and 3799 strains ( figure a1 ) .
results showed that the osaka and 3799 strains had deletions at nt 681704 and 717727 in contrast with the fermon strain .
moreover , a 1-nt deletion in osaka strains was identified at nt 641 in contrast with the fermon and 3799 strains .
because 14 patients with ev68 were detected during 20062009 ( 8) , detection of 15 patients with ev68 during a 4-month period suggests an ev68 epidemic in the summer of 2010 in japan .
phylogenetic analysis with vp1 sequences showed that osaka strains differed genetically from previously reported strains . for precise analysis of osaka , fermon , and 3799 strains ,
results showed that osaka strains more closely resembled the 3799 strain than the fermon strain .
alignment of partial 5 utr sequences showed that osaka and 3799 strains had deletions in 2 regions in contrast with the fermon strain , and the amplicon was shorter than expected .
the 5 utr of enterovirus contains an internal ribosome entry site ( 10 ) that is associated with translational efficiency and virulence of the enterovirus ( 11,12 ) .
deleted regions of osaka strains appear to be in the flanking region between the internal ribosome entry site and an open reading frame ( 1 ) .
detection of ev68 in numerous patients was reported in france during 2008 ( 4 ) and italy during 20082009 ( 13 ) . because this deletion was found in the 3799 strain in 1998 , recent detection of ev68 in japan
reported that serum samples from 281 pregnant women in finland in 1983 , 1993 , and 2002 had high titers of neutralizing antibody against ev68 ( 14 ) .
all ev68-positive patients in this study were < 5 years of age and had lower respiratory tract inflammation .
seroepidemiologic studies in finland showed that most adults might have been previously infected with ev68 and therefore might have neutralizing antibodies ( 14 ) . increased detection of ev68 , especially in infants and children
this result indicates that ev68 can replicate in blood and may damage the central nervous system .
ev68 was detected in cerebrospinal fluid of a young adult patient with acute flaccid paralysis ( 5 ) .
epidemiologic data for ev68 are lacking , and little information is available regarding virologic characteristics .
if one considers results of phylogenetic analyses and nucleotide and amino acid identities , evolutionary changes might have occurred in ev68 .
our results show the potential role of ev68 infection in infants and children with rtis .

Answer:
enterovirus 68 strains were detected in 14 specimens from children with respiratory tract infections and 1 specimen from a child with febrile convulsions during 2010 in osaka , japan .
 these strains had deletions in the 5 untranslated region and were genetically different from reported strains .
 this virus is associated with respiratory tract infections in japan .


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Thiopeptide Pyridine Synthase TbtD Catalyzes an Intermolecular Formal Aza-Diels-Alder Reaction

Paper sections:

The Diels-Alder (DA) reaction has been a staple of organic synthesis since its discovery by Otto Diels and Kurt Alder in 1928.1 Numerous total syntheses have exploited different versions of this typically concerted cycloaddition reaction and related transformations to efficiently construct carbon frameworks and stitch together complex organic scaffolds.2 In recent years, it has become apparent that similar chemistry is employed widely in the biosynthetic pathways of complex natural products.3–6 Several enzymes have been found to catalyze DA or DA-like reactions, including PyrI4 in pyroindomycin biosynthesis, SpnF in spinosyn biosynthesis, and LovB in lovastatin biosynthesis, among others.7–11 In many of these cases, the enzymes work to activate, accelerate, and/or direct the stereochemical outcome of an otherwise spontaneous cycloaddition reaction. As a result, reactions catalyzed by these Diels-Alderases can be highly substrate dependent and their biocatalytic utility is limited.

Pyridine synthases in thiopeptide biosynthesis provide unique examples of what is thought to be an enzyme catalyzed aza-DA. The biosyntheses of thiopeptides are similar to other ribosomally synthesized and post-translationally modified peptides (RiPPs) in that the C-terminal 'core' of a precursor peptide is transformed into the mature natural product by a suite of peptide modifying enzymes that are recruited by an N-terminal 'leader' peptide. 12,13 Pyridine synthases are responsible for the late stage formation of the class-defining nitrogenous heterocycles at the core of the thiopeptide pharmacophores.14–16 The key reaction is thought to entail an intramolecular formal [4+2] cycloaddition between two dehydroalanines (Dhas) followed by elimination of water and leader peptide (LP) to yield a tri-substituted pyridine core (Fig. 1a).17,18 In contrast to other DAs, this reaction is non-spontaneous and incurs a significant thermodynamic penalty due to the inactivated nature of the reaction subcomponents. Synthetic versions of this cycloaddition are low yielding and require high temperatures.19

The in vivo manipulation of thiopeptide biosynthetic gene clusters has demonstrated that pyridine synthases are very promiscuous enzymes and can be used to generate a variety of thiopeptide derivatives with different sized macrocycles and pyridine substituents.20–25 More specifically, enzymatic macrocyclization is independent of any structural preorganization imposed by the core peptide, as neither its length nor rigidity prevent cyclization.23 Thus we reasoned that pyridine synthases might be able to catalyze an intermolecular reaction between isolated 2π and 4π components. Such a reaction would provide perhaps the most extreme example of substrate promiscuity and support a two-site model of substrate recognition. Therefore, we sought to test whether pyridine synthases TclM or TbtD, from the biosynthetic pathways of thiocillin (1) and thiomuracin (2), respectively, could catalyze an intermolecular reaction (Fig. 1b). Optimization of the enzyme reaction conditions was an important initial step to test this hypothesis because our previous work showed that the enzymes could be slow and several modifications known to be permitted in vivo either refused to be cyclized in vitro and/or generated by-products.26

We first looked to improve the in vitro activity of TclM and TbtD by investigating the influence of pH on the rate of pyridine formation. Several steps of the proposed mechanism could be influenced by pH: (1) tautomerization of the enamide to iminol, (2) elimination of water and (3) aromatization (Fig. 1a). We used our previously described solid-phase strategy to prepare substrates for TclM and TbtD (compounds 3 and 4, respectively, Fig. 2a, b) based on their respective precursor peptides, TclE and TbtA (Fig. 1c).26 Each substrate consisted of a simplified core with a minimal LP fragment that was previously found to be sufficient for complete processing.14,26 The TclM substrate (3), was synthesized with a 10-residue LP, while the TbtD substrate (4), had a 15-residue LP (Fig. 2a, b). Enzymatic reactions were monitored at neutral and basic pH by measuring the distinctive absorbance of the newly forming, tri-substituted pyridine at 350nm over time. Reaction rates were calculated based on standard curve (see SI). A significant increase in rate was observed for each enzyme at pH 9.0 (Fig. 2c). Specifically for TbtD, a nearly 10-fold increase in kcat was observed from pH 7.2 to 9.0 (Fig. 2d, S1). Although kcat at pH 9.0 is still generally considered low, it is comparable to other late stage RIPP-modifying enzymes.27–32

Next, we assessed whether pH influenced substrate binding. We measured the dissociation constant, Kd for TbtA bearing the 15-residue LP and MBP-TbtD via fluorescence polarization assay. A non-reactive substrate for TbtD, with alanines instead of Dhas, was synthesized and derivatized with fluorescein isothiocyanate (FITC) at the N-terminus (5). Kd's were determined at pH 7.2, 8.0 and 9.0 (Fig. 2d, S2). Effects of pH on Kd were minor compared to those on kcat. At pH 7.2, a Kd of 3.2μM was measured whereas values of 3.9 and 7.1μM were observed at pH 8.0 and 9.0 respectively. These data suggest that the pH does not significantly influence substrate binding.

Due to the pronounced binding affinity of TbtA's N-terminal 16-residue LP for TbtD,33 we sought to determine whether this region of the LP might further enhance the reaction rate by allosteric regulation in trans. Studies have shown that this region contribute much of the full-length leader LP binding affinity to TbtD (Kd = 1.3μM),33 but is not strictly essential for enzymatic processing.16,26 The 16-residue N-terminal fragment (6) was synthesized by SPPS and reaction rate for substrate 4 was measured at pH 7.2 and 9.0 in presence or absence of 6. No appreciable change in rate was observed (Fig. S3). These data suggest that the N-terminal LP fragment does not act as an allosteric modulator. In the context of full length TbtA, this fragment's higher affinity may allow the LP to bind first, thereby increasing local concentration of the core around the active site to facilitate faster modification.

As an initial test of TbtD's improved substrate promiscuity under the optimized reaction conditions we assessed its ability to cyclize TbtA LP mutants. Previously, alanine scanning mutagenesis had been used to investigate LP binding to TbtD16,33 but not substrate processing. We reasoned that similar experiments might identify residues within the LP that are important for catalysis in addition to acting as a metric for promiscuity. A suite of 16, largely alanine-substituted, LP variants were prepared in parallel by solid-phase peptide synthesis (SPPS, see SI). The LP variants were separately tested at pH 7.2 and 9.0, and LCMS analysis revealed several differences (Table 1, Fig. S4a–q). Overall, 12 of the 16 substrates were processed at neutral pH, while 15 were cyclized under basic pH. Interestingly, only the H27A LP variant failed to cyclize under either condition. These data indicate that TbtD exhibits broader substrate promiscuity under basic pH.

With the enhanced activity of pyridine synthases confirmed, we sought to test whether TclM or TbtD could catalyze an intermolecular reaction. 2π components for both TclM and TbtD were prepared by SPPS and consisted of the corresponding minimal leader sequences with a C-terminal Dha-thiazole. The TclM 4π component was synthesized via SPPS following the same synthetic strategy that was used to prepare the intramolecular substrates. The TbtD 4π component was synthesized in solution from thiazole building blocks following standard peptide coupling procedures (see SI). In either case, each 4π component was designed to present the amide bond and Dha proposed to be involved in the cycloaddition plus two-to-three modified residues flanking either side. Incubation of each set of substrates with their respective pyridine synthases at pH 7.2 for 21 hrs yielded only trace amounts of product by LCMS. At pH 9.0, we again observed only trace amounts of product in reactions with TclM (Table S1). However, TbtD cleanly consumes both components and produces a new UV peak with characteristic absorbance at 350 nm and [m/z] consistent with a fully formed pyridine product (Fig. 3, S5a). The intermolecular reaction was scaled up and the identity of the product was confirmed by 1H and 13C NMR. TbtD is capable of recognizing the 2π and 4π reaction partners separately, without need for tethering between them, suggesting that an exceptionally broad array of macrocycles could likely be prepared by this enzyme.

In order to further define the limits of the TbtD-catalyzed intermolecular reaction, we prepared a small library of 2π and 4π substrates. With respect to the 2π component, previous LP truncation experiments and the above LP variants have defined the important residues in the LP so we focused further variation on the C-terminal side on the Dha. The thiazole (Thz) was changed to an oxazole (Oxz, Fig. 4b, entry 2) or removed entirely (Fig. 4b, entry 3). These 4π substrates were again synthesized via solution-phase chemistry and Dhas were installed either through alkylation-elimination chemistry of cysteine thiols or via mesylation-elimination of serine alcohols (see SI). As with the 2π substrates, thiazoles were iteratively changed to oxazoles and residues flanking the necessary Dha were removed to isolate the crucial components of the 4π substrate. For each new reaction, a percent conversion was calculated based on LCMS analysis and the rate of cyclization was measured by change in absorbance at 350 nm over time relative to a standard curve of purified product (Fig. 4b, S5a–h, S6). The results illustrate several key requirements for intermolecular substrates (summarized in Fig. 4a): (1) the C-terminal heterocycle must be present in the 2π component (Fig. 4b, entry 3), but a thiazole can be exchanged for an oxazole without significantly perturbing the rate or conversion (Fig. 4b, entry 2); (2) TbtD is sensitive to changes to both the N- and C-termini of the 4π component (comparing entry 1 to 6, 7 and 8 in Fig. 4b); (3) the bisazole motif is critical for cyclization; truncation to a single thiazole results in no product (Fig. 4b, entry 8); (4) removal of the C-terminal Dha results in no product – this Dha can be replaced with an alanine, albeit at significant cost to overall rate (Fig. 4b, entries 6 and 7); (5) in all 4π substrates, exchanging thiazoles for oxazoles is tolerated but there is a decrease in efficiency in each case (comparing entry 1 to 2, 4 and 5 in Fig. 4b). Ultimately, all permissible reactions could be forced to full conversion with higher enzyme loadings, allowing isolation and structural confirmation of products by 1H and 13C NMR. These data demonstrate TbtD is tolerant of major changes to nearly every residue outside of the two Dhas undergoing pyridine ring formation.

In conclusion, we found that the thiomuracin pyridine synthase TbtD is capable of catalyzing an intermolecular pyridine formation in addition to its cognate intramolecular reaction. The intermolecular reaction proved possible only under rate-enhancing alkaline conditions, which allow an approximate 10-fold increase in enzyme turnover (kcat) while minimally affecting substrate binding (Kd). The thiocillin pyridine synthase, TclM, observed similar base-catalyzed rate-enhancement but could not perform an intermolecular reaction, suggesting that different families of pyridine synthases may have distinct substrate requirements. The intermolecular chemistry of TbtD provides evidence that pyridine synthases use a two-site model to engage and process their precursor peptides; this reaction is a strong indicator of this enzyme family's broad promiscuity, suggesting that their use as biocatalysts could be extended beyond natural thiopeptide scaffolds, to allow larger ring sizes, incorporation of non-natural functionality or even novel linear substrates. The intermolecular reaction may be of use in elucidating the mechanism of these enzymes and may provide a barometer for evaluating new pyridine synthases for biotechnology applications.

Answer: Thiopeptide pyridine synthases catalyze a multistep reaction involving a unique and non-spontaneous intramolecular aza-[4+2] cycloaddition between two dehydroalanines to forge a tri-substituted pyridine core. We discovered that the in vitro activity of pyridine synthases from the thiocillin and thiomuracin pathways are significantly enhanced by general base catalysis and that this broadly expands the enzymes substrate tolerance. Remarkably, TbtD is competent to perform an intermolecular cyclization in addition to its cognate intramolecular reaction, underscoring its versatility as a biocatalyst. These data provide evidence that pyridine synthases use a two-site substrate recognition model to engage and process their substrates.


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
clinical practice gives students the opportunity to make decisions , apply theories , prioritize those decisions , learn time management , and provides them with a chance to practice their clinical skills ( 2 , 3 ) . in a supportive learning environment ,
clinical teachers encourage students to be independent in their learning and they advise them to be self - reliant ( 4 , 5 ) .
however , some earlier studies conducted in iran have shown that clinical learning is usually ineffective for nursing students ( 6 ) , students experience high levels of anxiety ( 6 ) , nursing instructors are mostly inexperienced , and clinical learning fails to integrate theory and practice ( 7 )
. however , few studies are available on the reasons behind the ineffectiveness of clinical learning in nursing education .
this study aimed to find out the factors that can impede nursing students clinical learning .
participants were purposively selected among the nursing students who were studying in their seventh semester of the baccalaureate program in 2014 and who had clinical rotations in the hospitals affiliated to bushehr university of medical sciences .
after the researchers explained the objectives of the study to the participants , 12 students , out of 30 , volunteered to participate and to keep reflective journals . in a briefing session , the first researcher gave them a notebook and presented them with a verbal description of how to complete the journaling task .
the students were asked to write in their journals about their own experiences , important learning events , attitudes , feelings , and their own opinions on their clinical learning experiences in after passing a week of their practical course in each ward .
they were asked to return these anonymous journals to the researcher at the end of each week .
46327 ) and review board of bushehr university of medical sciences approved and granted the proposal of this study .
all of the participants signed a written informed consent form and were assured that their written texts would not be shown to any persons other than the researchers and would not affect their clinical evaluation scores .
thus , the researchers received each journal from the participants , and then they considered them carefully .
analyses consisted of identifying , coding , and summarizing themes according the approach suggested by graneheim and lundman ( 8) . in order to evaluate the data s trustworthiness , the researchers gave summarized results to a few participants to confirm the credibility of the data analysis .
the established relationship between the researchers and participating students facilitated a trust - based relationship between the parties in relation to data generation and treatment .
credibility was also enhanced because of the prolonged engagement of the researchers with participants and having experience in the practical field as an instructor .
participants were purposively selected among the nursing students who were studying in their seventh semester of the baccalaureate program in 2014 and who had clinical rotations in the hospitals affiliated to bushehr university of medical sciences .
after the researchers explained the objectives of the study to the participants , 12 students , out of 30 , volunteered to participate and to keep reflective journals . in a briefing session , the first researcher gave them a notebook and presented them with a verbal description of how to complete the journaling task .
the students were asked to write in their journals about their own experiences , important learning events , attitudes , feelings , and their own opinions on their clinical learning experiences in after passing a week of their practical course in each ward .
they were asked to return these anonymous journals to the researcher at the end of each week .
46327 ) and review board of bushehr university of medical sciences approved and granted the proposal of this study .
all of the participants signed a written informed consent form and were assured that their written texts would not be shown to any persons other than the researchers and would not affect their clinical evaluation scores .
thus , the researchers received each journal from the participants , and then they considered them carefully .
analyses consisted of identifying , coding , and summarizing themes according the approach suggested by graneheim and lundman ( 8) . in order to evaluate the data s trustworthiness , the researchers gave summarized results to a few participants to confirm the credibility of the data analysis .
the established relationship between the researchers and participating students facilitated a trust - based relationship between the parties in relation to data generation and treatment .
credibility was also enhanced because of the prolonged engagement of the researchers with participants and having experience in the practical field as an instructor .
the participants believed that interpersonal communication between students , nurses , teachers , physicians , and patients was one of the most important factors affecting clinical learning . from the students point of view
, a positive and friendly relationship between students , nurses , and instructors affects the clinical learning environment and increases their self - confidence and learning .
students described that communication with their classmates in the educational environment was positive and satisfying .
my friend and i always are together , and ask each other questions that we have , and this is good .
 however , relationships were not respectful from the side of the qualified nurses , and this affected the students motivation to learn .
some nurses frowned at me , when i asked them a question .  from the participants point of view , some nurses did not trusted the students ' work , and they blamed them when anything bad happened in the ward .
participants emphasized that the competence of the clinical instructors and staff nurses -as a role models- was a crucial factor affecting their learning in the clinical field .
to the students , their instructors kindness , knowledge , clinical skills , expertise , and self - efficacy were among the main characteristics that made them good role models .
some instructors have sufficient knowledge and skills , so they have a higher self confidence level , and they help us ( students ) to understand how to do our duties . some of them say to follow whatever staff do . in this
 however , the majority of the students believed that the lack of clinical experience among instructors was the main barrier that decreased their competency to train students effectively .
nonetheless , although they were technically skillful , they did not always have a caring attitude and sometimes performed procedures without upholding any standards .
participants revealed that there is a theory - practice gap in the clinical setting , and this hindered their clinical learning .
the participants indicated that they confronted problems such as confusion about how to do procedures based on theoretical knowledge or like nurses in real situations .
one student wrote :  we did nt see many things that we have learnt in theoretical class .
if we follow standards , the nurses may laugh us and i dread this .
participants wrote in their journals that the nurses were often unaware of educational objectives and the students learning needs ; further , their expectations of the students were not the same as the teachers. one of them wrote :  the staff nurses demand that we do their routine tasks , such as checking vital signs and changing linens .
these are not useful for us , because these are repeated each day and we learnt them well , but we did nt learn some special procedures , like cpr .
the participants believed that interpersonal communication between students , nurses , teachers , physicians , and patients was one of the most important factors affecting clinical learning . from the students point of view
, a positive and friendly relationship between students , nurses , and instructors affects the clinical learning environment and increases their self - confidence and learning .
students described that communication with their classmates in the educational environment was positive and satisfying .
my friend and i always are together , and ask each other questions that we have , and this is good .
 however , relationships were not respectful from the side of the qualified nurses , and this affected the students motivation to learn .
some nurses frowned at me , when i asked them a question .  from the participants point of view , some nurses did not trusted the students ' work , and they blamed them when anything bad happened in the ward .
participants emphasized that the competence of the clinical instructors and staff nurses -as a role models- was a crucial factor affecting their learning in the clinical field . to the students , their instructors kindness , knowledge , clinical skills , expertise , and self - efficacy were among the main characteristics that made them good role models .
some instructors have sufficient knowledge and skills , so they have a higher self confidence level , and they help us ( students ) to understand how to do our duties . some of them say to follow whatever staff do . in this
 however , the majority of the students believed that the lack of clinical experience among instructors was the main barrier that decreased their competency to train students effectively .
although they were technically skillful , they did not always have a caring attitude and sometimes performed procedures without upholding any standards .
participants revealed that there is a theory - practice gap in the clinical setting , and this hindered their clinical learning .
the participants indicated that they confronted problems such as confusion about how to do procedures based on theoretical knowledge or like nurses in real situations .
one student wrote :  we did nt see many things that we have learnt in theoretical class .
if we follow standards , the nurses may laugh us and i dread this .
participants wrote in their journals that the nurses were often unaware of educational objectives and the students learning needs ; further , their expectations of the students were not the same as the teachers. one of them wrote :  the staff nurses demand that we do their routine tasks , such as checking vital signs and changing linens .
these are not useful for us , because these are repeated each day and we learnt them well , but we did nt learn some special procedures , like cpr .
the current study has shown that , despite the crucial role of appropriate relationships in students clinical learning experiences , it is not enough .
this finding was in line with findings of jahanpour et al . , who studied clinical decisionmaking in senior nursing students ( 2 ) .
according the participants in this study , the competence of their clinical instructors and the theory - practice gap were among the most important factors affecting them and their learning in clinical settings .
some earlier studies have also pointed out the role of clinical instructors and staff nurses as role models for nursing students learning in clinical setting ( 6 , 9 , 10 ) . in iran , many experienced nursing instructors who hold master s or phd degrees are reluctant to participate in clinical education , and so this role is mostly assigned to inexperienced , newly graduated nurses with master s degrees , or those who are still master s degree students .
these people are not ready to fulfill their role as competent role models . on the other hand , as cheraghi et al .
( 7 ) reported , due to the domination of task - oriented work in clinical settings , nurses clinical behaviors can not support nursing students efforts to integrate theory and practice .
this study was only conducted in one nursing school , and this might limit the generalizability of the results .
however , based on out findings , we can say that nursing students lack sufficient clinical learning due to unsupportive and inappropriate communication running throughout clinical settings , they lack effective role models , and they are harmed by the theory - practice gap . restructuring the healthcare setting so that experienced nursing instructors are encouraged to enter and participate in clinical settings , establishing appropriate workshops for preparing inexperienced nursing instructors for their roles as clinical instructors , and implementing appropriate strategies to motivate staff nurses to take part in the education of nursing students might help in decreasing the barriers to effective learning in clinical settings .

Answer:
backgroundclinical training is an integral part of nursing education ; however , some studies have shown that it is not always efficient.objectivesthis study aimed to find out the factors that can impede nursing students clinical learning.materials and methodsin this qualitative study , data were collected via reflective journal writing .
 purposeful sampling was used , and 12 senior nursing students were recruited to the study .
 the data were analyzed using a content analysis method.resultsthree main categories were derived , including inappropriate communication , ineffective role models , and theory - practice gaps .
 students perceived that inappropriate communication between instructors , staff members , and students had the greatest impact on student learning .
 the competence of clinical instructors and staff is an important factor affecting students training
 . the clinical learning environment does not always integrate theory and practice together.conclusionsnursing students did not experience effective clinical learning .
 having expert instructors and supportive communication are important factors in creating a clinical learning environment .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
when i hear the word quantitation , what comes to mind is the contrast between two famous 19th - century german scientists , alexander von humboldt and carl gauss , as described in measuring the world : a novel ( kehlmann , 2009 ) .
von humboldt was a great prussian explorer who made many discoveries , including electric eels , in his expeditions to south and central america , which included the casiquiare canal , which connects the orinoco and amazon rivers .
a man of extraordinary energy , he was the consummate quantitater  he measured the heights of mountains and the numbers of lice on the heads of natives .
gauss , as surveyor and astronomer for the kingdom of hannover , was also a quantifier , but with a different style .
charged with devising a practical method to survey on a spherical earth , he laid the foundation for a school of geometry that culminated in the work of riemann and the notion of curved space - time in einstein 's general theory of relativity .
the lesson here is that when you have a theory , measurement becomes very important and intellectually challenging .
have all the relevant parameters been measured ? have all the confounding complications been considered ?
does the theory really fit to the data ? how accurately have the underlying quantities ( parameters ) been measured ?
what is a model ? what is the difference ? in biology , we usually distinguish three types of model : conceptual models , mathematical models , and simulations ( bowne - anderson et  al . , 2013 ) .
they all serve the same general purpose : to explain more complex phenomena in terms of more elementary processes or molecular interactions .
this can be in the form of a cartoon or picture that conveys the author 's idea or explanation of his or her results .
but can it really explain the data ? usually , more work is needed to establish the plausibility of a conceptual model .
a mathematical model is the development of the conceptual model into a system of equations .
the postulates are identified ( often in the form of parameters ) , and the implications or predictions are derived by solving the equations . the equations usually describe the average behavior of a large number of interacting molecules or entities  a so - call mean - field theory ( although variances and other statistical properties can often also be calculated ) .
the solutions are then compared with the experimental measurements  the quantitation of the data . if the equations can be solved analytically , all is well and good because this usually indicates that the solution is simple , or at least familiar . if not , numerical solutions are readily provided by such programs as matlab ( www.mathworks.com ) .
the predictions of the model ( with appropriate parameters ) can then be used to quantitatively account for the experimental data .
this is the process of curve fitting , which can be used to ask whether the theory actually fits the data ( i.e. , establish plausibility ) and to measure the underlying parameters and their uncertainties . a simulation is a computer - based imitation of a system . like a mathematical model , a simulation postulates interactions between underlying molecules or entities . unlike
a mathematical model , however , a simulation models individual behavior ( rather than mean behavior ) and often needs to be repeated a large number of times to obtain an accurate measure of the average behavior .
simulations are especially valuable when modeling small - number systems , which can display highly stochastic behavior .
simulations can be used for establishing the plausibility of a conceptual model , and by changing the parameters , the simulator can experiment with the model to gain insight into how it works .
the first is that they often contain many details such as the precise initial conditions or the order of the interactions . in this sense
they are often like experimental results , which also depend on many details ( e.g. , the composition of the buffers ) . in light of well - documented cases in which the results of simulations depended on these details , it has been argued that a simulation should be treated like an experimental result in the sense that it should be confirmed in different laboratories before being accepted ( mitchell , 2009 ) .
a second potential limitation of simulation is that although it can establish plausibility of a mechanism , it might provide only limited insight .
this is especially the case if the system behavior is unexpected and the elementary interactions give rise to so - called emergent or collective behavior . in this case
, the behavior of the simulation may be as mysterious as the biological phenomenon being modeled , even when the simulator can probe the model by varying the model parameters ( analogous to performing wet experiments ) .
an alternative approach is to use so - called toy models ( or idea models ; mitchell , 2009 ) , which , while oversimplifying the system under study , are nevertheless simple enough to solve using a mathematical model , thereby providing insight into mechanism .
an example of a toy model is turing 's reaction - diffusion mechanism of pattern formation ( turing , 1952 ; gierer et  al . , 1972 ) .
i do not want the reader to think that simulations are always inferior to mathematical models . indeed , there are now very good algorithms that have solved many of the technical problems associated with simulations ( e.g. , the gillespie algorithm ; doob , 1945 ; gillespie , 2007 ) .
the physicist freeman dyson recounts attending a conference at which enrico fermi criticized the complexity of dyson 's model by quoting the mathematician john von neumann ( dyson , 2004 ) :  with four parameters i can fit an elephant , and with five i can make him wiggle his trunk .
actually , it is not so easy to model an elephant with four parameters , although we recently achieved it , even making the trunk wiggle with the fifth parameter ( mayer et  al . , 2010a ) !
if a model has a small number of premises or parameters that give rise to broad and/or unexpected implications , then we might call it a theory .
evolution  the modern evolutionary synthesis  is a theory because it makes a relatively small number of postulates yet predicts a very broad range of observations , including the laws of inheritance and models of population genetics .
it could be argued that other models , especially those underlying spatial oscillations ( e.g. , turing patterns ) and temporal oscillations ( e.g. , the cell cycle ; see later discussion ) , rise to the level of theories .
theories and models can be used to establish plausibility , sufficiency , or impossibility . they can also be used to measure .
the importance of establishing plausibility is illustrated by a recent example in which a textbook conceptual model was shown not to explain the observations .
myosin cortex was driven by a gradient of tension ( bray and white , 1988 ) . however , using experiments ( laser cutting ) and theory , it was found that cortical flow in the one - cell caenorhabditis elegans embryo is driven not by a gradient in tension but by a gradient of contractility ( i.e. , motor activity ) : in the direction of flow , there is no tension gradient , but , counterintuitively , in the transverse direction , there is a tension gradient but no flow ( mayer et  al . , 2010b ) !
this example shows the importance of developing a mathematical model ( and testing it ) to establish the plausibility of a conceptual model .
two examples of the use of theory to establish sufficiency are the action potential and the cell cycle . in a remarkable feat that serves as a foundation for neurobiology , hodgkin and huxley ( 1952 ) formulated and solved equations showing that the action potential in nerve cells can be accounted for by the voltage - dependent interactions between sodium and potassium conductances ( channels in the modern parlance ) .
the second example concerns the cell division cycle . following seminal discoveries showing the necessity of phosphorylation for controlling the transitions between phases of the cell cycle , tyson and novak ( 2011 ) showed the sufficiency of phosphorylation networks to drive the transitions . in other words
, they answered the question ,  what do you need to build a molecular switch
( answer : feedback and cooperativity ) , and , by doing so , they made the problem of the cell cycle  finite .  in the process , they made key predictions that were confirmed experimentally and they explained many phenotypes .
an excellent example of the use of theory to show impossibility is the prescient work of ken machin ( machin , 1958 ) .
he proved that the periodic bending motion of cilia and flagella ( such as sperm tails ) can not be driven by motor activity localized to the base of the cilium only : if the beating were driven by a whip - like process at the base , the amplitude would die out with a characteristic shape due to the damping from the fluid .
this shape is not consistent with the observed beating patterns , whose amplitudes are maintained along the length of the flagellum .
instead , he proposed motors all along the length , with a traveling wave of activity propagating from base to tip .
not bad , considering that the motor dynein had not been discovered ( gibbons and rowe , 1965 ) , nor was it known whether the filaments inside the flagellum ( the microtubules ) slid or contracted ( they slide ; satir , 1965 ) . of interest
showing impossibility is the most powerful use of mathematical models : it allows hypotheses to be falsified , which is difficult to achieve using simulations . in my work , i have used theory as a tool to measure molecular properties and interactions . for example , we used precise mechanical measurements on hair cells  the sensory receptors underlying the sensation of sound and acceleration  to estimate the force needed to open a single channel , the displacement associated with the opening of the channel 's gate , and the number of channels ( howard et  al . , 1988 ) .
in other work , we used theory to infer the bending stiffness of actin filaments and microtubules from an analysis of their shape fluctuations ( gittes et  al . , 1993 ) .
more recently , we showed how molecular interactions between kinesin motor proteins and microtubules can give rise to length - dependent microtubule depolymerization , which may play a key role in determining the size of organelles such as the mitotic spindle ( varga et  al . , 2006 , 2009 ;
these include the following :
 morphology : what determines the size , number , and shape of cells and organelles?signaling : how do molecules compute , and what is the role of spatial localization and compartmentalization?scaling : how do we bridge from one scale to another ? are there universal laws ?
morphology : what determines the size , number , and shape of cells and organelles ?
signaling : how do molecules compute , and what is the role of spatial localization and compartmentalization ? scaling : how do we bridge from one scale to another ? are there universal laws ?
especially important is to understand how variability is minimized within a cell to produce reproducible structures and signals , and amplified among cells to enlarge the number of stimuli to which a population of cells can respond .
there has been rapid development of single - molecule techniques , making it possible to manipulate individual molecules using optical and magnetic techniques and to visualize their activity inside cells using fluorescence microscopy . in this way
it is even possible to sequence single molecules of dna ( www.pacificbiosciences.com ) . at the whole - cell level
the developments are as impressive : image processing techniques can be used to segment single cells in tissues to measure shape and activity , their total protein assayed by mass spectrometry , and their genomes sequenced .
these studies have revealed remarkable cell - to - cell variability of  identical  cells .
hand in hand with these developments , we must have theory and models to make sense of the experimental results , as exemplified by gauss , rather than the collection of data for their own sake .
i predict that in the future , theory will drive biology as it does physics and engineering .

Answer:
quantitative biology is a hot area , as evidenced by the recent establishment of institutes , graduate programs , and conferences with that name .
 but what is quantitative biology ? what should it be ? and how can it contribute to solving the big questions in biology ?
 the past decade has seen very rapid development of quantitative experimental techniques , especially at the single - molecule and single - cell levels . in this essay
 , i argue that quantitative biology is much more than just the quantitation of these experimental results . instead , it should be the application of the scientific method by which measurement is directed toward testing theories .
 in this view , quantitative biology is the recognition that theory and models play critical roles in biology , as they do in physics and engineering . by tying together experiment and theory ,
 quantitative biology promises a deeper understanding of underlying mechanisms , when the theory works , or to new discoveries , when it does not .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:

 measuring performance of health systems is an essential tool for health policy - makers to conduct analysis and track change .
the 2000world health organization ( who ) report reflects that promoting health status , fairness in financing and responsiveness are the three main goals of evaluating health system performances ( 2 ) .
responsiveness refers to the ability of a health system to respond to the legitimate expectations of the population ; this is associated with the non - medical aspect of the health system and environment in which the people are treated ( 2,3 ) .
" respect for human right " and " client - orientation " are two broad categories of responsiveness .
furthermore , respect for human right consists of dignity , autonomy , communication and confidentiality ( 2,4 ) .
client orientation includes prompt attention , quality of basic amenities and access to social support networks as well as choice of provider . in 2000 , iran s health system was ranked 100th in terms of responsiveness ( 2,5 ) .
prompt attention and dignity were the most important domains of responsiveness of health systems for the iranian populations ( 6 ) .
besides , urgent and special attention was recommended to improve the responsiveness of the health system ( 7,8 ) .

 in a survey on health system responsiveness in tehran ,
more than 90% of the households believed that responsiveness was very important ( 5 ) .
in addition , it was reported that responsiveness was better for outpatient care than inpatient care ( 9 ) .
most of the studies on health care responsiveness have focused on household survey , and only a few studies were conducted to address the responsiveness of a health system to inpatient care ( 5,6,10,11 ) .
moreover , there is a gap in the concerning patients views on health system responsiveness in iran .

the 11th government , elected in june 2013 , took health as the top priority of its administration and has been implementing a health sector evolution plan ( hsep ) since may 6 , 2014 ( 12 ) .
hsep is a national plan , with two main phases : the first phase relating to improving fair access to healthcare and quality of inpatient and outpatient care in hospitals and the second to the public health care ( 13 ) .
hsep aimed to provide the followings : health insurance coverage to all uninsured individuals , reducing out - of - pocket expenses for inpatient services , providing financial protection of patients with specific diseases and poor patients , encouraging medical doctors to stay in deprived areas through motivational policies , improving quality of care through increasing specialists , and improving hospital amenities and lodging services ( 13,8 ) .
this study aimed at examining the effect of hsep on health system responsiveness in kermanshah , western iran .
the findings may contribute to improvements in the responsiveness of the health system in this area of iran .

 this was a cross - sectional study conducted on the responsiveness of the hospitals in admitted patients in kermanshah in 2015 .
the city has seven public university hospitals with a total number of 1,570 active beds and two private hospitals .
data were collected from six public university hospitals with the exception of the seventh university hospital , which was a psychiatry hospital .
a sample of 335 patients was calculated using the formula for single population proportion at 50% proportion of responsiveness ( as no evidence was available from similar studies in the area ) , 5% level of significance and 0.05 margin of error .
the proportionate allocation to population size technique was employed to collect data from each hospital .
at least three days hospitalization by a patient and age above three years were the inclusion criteria whilst patients who refused to participate or admission in intensive or critical care units were excluded .

data were collected using standard world health survey(whs ) questionnaire , which was developed by world health organization ( who).this questionnaire is a valid , reliable and comparative instrument that contains questions about the  importance of responsiveness domains from an inpatient s point of view ,  health services utilization and  people 's view about the responsiveness domain of inpatient services ( 14 ) .
items in each component of responsiveness were as follows : prompt attention ( 2 items ) ; communication ( 2 items ) ; human gentility and dignity ( 2 items ) ; patient s participation in decision - making and autonomy ( 2 items ) ; confidentiality and trust ( 2 items ) ; choice of provider ( 1 items ) ; quality of basic amenities ( 2 items ) ; and access to social support ( 2 items ) . in this study ,
responsiveness of the hospitals was considered as a dependent variable while the socio - demographic variables of the patients were the independent variables .
we used a five - point likert scale where 5was very important / very good , and 1 represented least important / very poor .
the responsiveness score for each domain was obtained by dividing the sum of the scores within the domain by the number of items in the likert scale .
the stata version 12 statistical package was used to analyze the responses of a five - point likert scale data .
the frequency distribution , ranges and mean ( sd ) were used to describe the data . the principal component analysis ( pca )
similar to another study in iran ( 5 ) , we used 0.4 and above as a cutoff for factor loading in the pca .
the overall relationship between the socio - demographic variables and health system responsiveness was checked by chi - square test .

 this was a cross - sectional study conducted on the responsiveness of the hospitals in admitted patients in kermanshah in 2015 .
the city has seven public university hospitals with a total number of 1,570 active beds and two private hospitals .
data were collected from six public university hospitals with the exception of the seventh university hospital , which was a psychiatry hospital .
a sample of 335 patients was calculated using the formula for single population proportion at 50% proportion of responsiveness ( as no evidence was available from similar studies in the area ) , 5% level of significance and 0.05 margin of error .
the proportionate allocation to population size technique was employed to collect data from each hospital .
at least three days hospitalization by a patient and age above three years were the inclusion criteria whilst patients who refused to participate or admission in intensive or critical care units were excluded .

 data were collected using standard world health survey(whs ) questionnaire , which was developed by world health organization ( who).this questionnaire is a valid , reliable and comparative instrument that contains questions about the  importance of responsiveness domains from an inpatient s point of view ,  health services utilization and  people 's view about the responsiveness domain of inpatient services ( 14 ) .
items in each component of responsiveness were as follows : prompt attention ( 2 items ) ; communication ( 2 items ) ; human gentility and dignity ( 2 items ) ; patient s participation in decision - making and autonomy ( 2 items ) ; confidentiality and trust ( 2 items ) ; choice of provider ( 1 items ) ; quality of basic amenities ( 2 items ) ; and access to social support ( 2 items ) . in this study ,
responsiveness of the hospitals was considered as a dependent variable while the socio - demographic variables of the patients were the independent variables .
we used a five - point likert scale where 5was very important / very good , and 1 represented least important / very poor .
the responsiveness score for each domain was obtained by dividing the sum of the scores within the domain by the number of items in the likert scale .

 the stata version 12 statistical package was used to analyze the responses of a five - point likert scale data .
the frequency distribution , ranges and mean ( sd ) were used to describe the data . the principal component analysis ( pca )
similar to another study in iran ( 5 ) , we used 0.4 and above as a cutoff for factor loading in the pca .
the overall relationship between the socio - demographic variables and health system responsiveness was checked by chi - square test .

 three hundred thirty five , 190 ( 56.7% ) male and 145 ( 43.3% ) female , patients with the mean ( sd ) age of 41.5 ( 2.36 ) yrs . and the age range of 3 - 92 yrs.were included in the study . of the respondents ,
92.8% had health insurance coverage , and 44.7 % were illiterate ( table 1 ) .

 the respondents rank on the level of importance of the health system responsiveness based on the domains of the responsiveness questionnaire is shown in fig .
the proportion of patients who rated the responsiveness of the hospitals as important or very important based on quality of the basic amenities , communication and dignity domains accounted for 94% , 91% and 90% , respectively .
the social support domain was considered as the least domain as only 77% of the patients rated this domain as important or very important .

proportion of the participants who rated the responsiveness domain as important / very important
 the mean performance of each domain of the health system responsiveness is shown in table 2 .
the best and worst performance for domains of dignity and autonomy were 82.2 and 62.5 , respectively .

the findings indicated that 68% of the variance of the overall responsiveness score was explained by four components .
the first component which contained communication , dignity and autonomy explained 31.4% of the variance ; the second component contained confidently and social support and explained17.6 % of the variance ; the third component contained quality of basic amenities and choice domain and explained 11% of the variance and the fourth component contained dignity domain only and explained8% of the variance .

the empirical analysis revealed no significant association between total health system responsiveness scores and gender , education , age , health insurance coverage , and working status of the respondents .

 this study was the first of its type after health sector evolution plan ( hsep ) .
the aim of this study was to describe health system responsiveness in western part of iran .
however , several studies have been conducted on health system responsiveness before hsep elsewhere ( 5,10,11,16 ) .
responsiveness of the health system is the result of interactions between health system agents and the patients ( 16 ) , which is related to the patient s well - being ( 17 ) .
the well - being of the patients is influenced by health system and the health system s responsiveness to the patients ( 18 ) .

quality of basic amenities , dignity , communication and prompt attention received higher scores in terms of importance .
this implies that from patient s point of view , these domains are more important than other domains of responsiveness . in addition , compared to previous studies in iran , patients kept their preferences about responsiveness domains .

 in this study ,
the mean performance of each domain of the health system responsiveness was not much different except for autonomy that was rated the least . in another study that assessed the responsiveness of hospitals to inpatient care in zanjan reported an overall responsiveness score of 58.4 ( 10 ) .
similarly , karami - tanha et al . found hospital responsiveness score of 57 to patients with heart failure ( 15 ) .
furthermore , a household survey on responsiveness of health systems to outpatient and inpatient services in tehran reported 70.6 responsiveness score ( 5 ) . generally , the overall score of responsiveness of the hospitals to inpatient services in our study was higher than the scores reported in previous studies in iran .
besides , hospital responsiveness scores in our study were higher than the scores reported in studies elsewhere ( 9,21,22 ) , but lower than the scores reported in germany ( 23 ) .

 in this study , dignity , confidentiality , and quality of basic amenities had the best performance .
this finding is in line with the reports of several studies ( 11,15,17,18 ) , and with that of rashidian et al . , but the quality of basic amenities in their report was the second worst performance ( 5 ) . in  previous  iranian studies , social support / confidentiality/ dignity ( 11 ) , dignity/ confidentiality/ prompt attention/ ( 5 ) , dignity/ confidentiality/ prompt attention ( 15 ) confidentiality/ communication / prompt attention ( 10 ) were reported as the best performing domains . unlike our study , a study in china reported social support to be the best performance domain ( 24 ) .
confidentiality and dignity domains achieved highest scores in the health system of iran before and after hsep .
in addition , a high score in the quality of basic amenities means that the rooms in the hospitals were clean and there were enough waiting and examination rooms .
in fact , after hsep , public hospital rooms were renovated and lodging and welfare equipment were purchased ( 12 ) . in this study , the autonomy domain had the worst performance score followed by choice domain .
this finding is similar to the findings reported in several other studies ( 5,10,15,22,23 ) . in the above - mentioned study of iran , autonomy/ quality of basic amenities ( 5 ) , autonomy/ communication ( 11 ) , choice/ autonomy ( 10 ) , and autonomy / choice received the least score ( 15 ) . in this study ,
performance of hospitals with respect to communication , prompt attention , social support , choice and autonomy were rated 4th to 8 , respectively .
therefore , providing training for the health care providers and improving their knowledge is necessary to achieve a higher score in the autonomy and choice domains .

 in this study
, the principal component analysis revealed that responsiveness for inpatients care included communication dignity/ autonomy , confidently/ social support , and lastly quality of basic amenities / choice as the main factors . in a study conducted in taiwan , five factors of respect , access , confidentiality , basic amenities and social support were extracted .
these five factors revealed acceptable internal consistency , four of which were significantly correlated with the overall responsiveness score ( 25).in other studies , communication , autonomy and confidentiality were the main factors ( 5,21 ) . while the majority of the above - mentioned reports included both inpatient and outpatient cares , this study was limited to inpatient care and university hospitals .

 this study indicated a high rate of overall responsiveness score of each of the domains compared to other similar previous studies in iran .
although it is difficult to reach a conclusion , our findings may show better responsiveness of the health system than the previous reports . the relatively higher responsiveness of the hospitals in the " quality of basic amenities " domain may be a direct result of huge resources use that was allocated to the hospitals during hsep .
finally , improvement in  client - oriented  domains of health system responsiveness such as quality of basic amenities and prompt attention may require large investments and additional resources , while improvement in

Answer:
background : responsiveness is one of the three main goals of the health system introduced by world health
 organization .
 this study aimed at examining health system responsiveness after health sector evolution plan in
 kermanshah , western iran .

 methods : a sample of 335 hospitalized patients was selected using proportionate allocation to population size
 method in the city of kermanshah ( iran ) in 2015 .
 world health survey ( whs ) questionnaire was used to collect
 data .
 data were analyzed using descriptive statistics and principal component analysis by stata 12 .

 results : the overall health system responsiveness score was 72.6 .
 the best and worst performance for domains
 of dignity and autonomy were 82.2 and 62.5 , respectively .
 socio - demographic variables of the patients
 had no significant effect on the total health system responsiveness score .
 the principal component analysis findings
 indicated that 68% of the variance of the overall responsiveness score was explained by four components .

 conclusion : the overall responsiveness score of each of the domains was higher than that of other similar
 previous studies in iran . although it is difficult to reach a conclusion , our findings may show better responsiveness
 of the health system compared to the previous reports