The system of partial differential equations governing the unsteady hydromagnetic boundary-layer flow along an electrically conducting cone embedded in porous medium in the presence of thermal buoyancy, magnetic field, heat source and sink effects are formulated. These equations are solved numerically by using an implicit Finite-Difference Method. The effects of the various parameters that are source/sink parameter, porous medium parameter, Prandtl number, mixed convection parameter and magnetic Prandtl number on the velocity, temperature profiles, transverse magnetic field are predicted. The effects of heat source and sink parameter on the time-mean value as well as on transient skin friction; heat transfer and current density rate are delineated especially in each plot. The extensive results reveal the existence of periodicity and show that periodicity becomes more distinctive for source and sink in the case of the electrically conducting cone. As the source and sink contrast increases, the periodic convective motion is invigorated to the amplitude and phase angle as reflect in the each plot. The dimensionless forms of the set of partial differential equations is transform into primitive form by using primitive variable formulation and then are solved numerically by using Finite Difference Scheme which has given in literature frequently. Physical interpretations of the overall flow and heat transfer along with current density are highlighted with detail in results and discussion section. The main novelty of the obtained numerical results is that first we retain numerical results for steady part and then used in unsteady part to obtain transient skin friction, rate of heat transfer and current density. The intensity of velocity profile is increased for increasing values of porosity parameter Ω, the temperature and mass concentration intensities are reduced due heat source effects. Several studies have been conducted on heat transport through a porous medium due to its industrial applications and numerous technical processes. Flows through porous medium are of particular interest because they are so common in nature and daily life. Water is saturated in porous materials such as sand and underground crushed rocks, which allows the fluid to move and be transported through the material under the influence of local pressure gradients. This fascination stems from the various practical applications that can be modeled or approximated, through porous medium such as packed sphere beds, high-performance building insulation, grain storage, chemical catalytic reactors, sensible heat storage beds and heat exchange between soil and atmosphere. Moreover, soil salt leaching, solar power collectors, electrochemical processes, filtering devices, insulation of nuclear reactors, regenerative heat exchangers, geothermal energy systems and many other areas. Convective heat transfer in porous medium is of much interest of research community engaged in different applied and engineering disciplines.et al. [Kamel  proposedet al.  investiget al. . Cortellet al.  encounteet al. .et al. [et al. [et al. [et al. [et al. [Sharma and Singh  predicteet al. . Pal andet al. . Analyze [et al.  conducte [et al. . Osman e [et al.  computed [et al.  discusse [et al. .et al. [et al. [The combined effects of a magnetic field and convective diffusion of species through a non-Darcy porous medium over a vertical non-linear stretching sheet in the existence of Ohmic dissipation and a non-uniform heat source/sink have been depicted by Pal and Mondal . For traet al. . The com [et al. . The mag [et al. . Pal and [et al.  discusseet al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [et al. [Chaudhary et al.  briefly et al.  examined [et al. . They no [et al. . Hayat e [et al.  investig [et al. . Suneeth [et al.  gave an  [et al.  examined [et al.  investig [et al. . By exer [et al. . Unstead [et al. . Later,  [et al. –37 discu [et al. –41.In keeping view the above literature, we interact with the phenomenon for unsteady mixed convective flow across the surface of electrically conducting cone embedded in porous medium in the presence of heat source and sink. The time dependent dimensionless equations which illustrate the hydromagnetic laminar flow along the surface of sphere are formulated. Further, we consider the motion along sphere within plume region-I with main stream velocity. By using Stokes condition we separate steady and unsteady part from the modeled partial differential equation. Later, the unsteady part is further splited in to real and imaginary part. First we secure numerical solutions for steady part and then used in unsteady part to calculate periodic skin friction, heat transfer, and current density along the surface of the cone embedded in porous medium. We also calculate fluid velocity, magnetic field and temperature profiles, to ensure the correctness of numerical results by satisfying the prescribed boundary conditions.x is measured along the surface and y is measured normally on the cone surface. The velocities u and v along the -direction, Hx represent the component of magnetic field at the surface of cone, Hy component is taking normal to the surface of cone and external fluid velocity of the cone is U. Moreover, magnetic field intensity proceeds exact at the surface of the cone. The form of governing dimensioned continuity, momentum, magnetic, and energy equations, as well as the boundary conditions are given as belowConsider a two-dimensional periodic mixed convection boundary-layer fluid flow along the surface of thermally and electrically conducting cone embedded in porous medium. The scheme of coordinates is shown in The dimensioned form of boundary conditions areThe following are the dimensionless system of coupled nonlinear partial differential equations:The dimensionless boundary conditions are:λ, represents porosity number and mixed convection dimensionless number, γ is Prandtl magnetic number, Prandtl parameter is Pr, Ho is the exact strength of the magnetic field at the surface and δ represents the heat generation absorption parameter.The third and fourth term on right hand side of Eq  which arω is takes the term U(τ) = 1+ϵeiωτ. The velocity of the fluid, magnetic field and temperature components u, v, hx, hy and θ are defined as the sum of steady and unsteady equations.The stream velocity under |ε|<<1, where ε presents a small magnitude periodic component and the frequency parameter O(ε0) and O(εeiωτ), using these orders from Eqs  and and19) au, v, θ, hx and hy respectively, where A, B, C and D are coefficient matrices for above mentioned unknown variables. Later, the coefficient matrices are solved by using Gaussian elimination technique. Convergence of the solutions was declared at each step by following.Here, Γ represent the field variable n represent the nth iteration.Where τs, heat transfer τt and current density τm along the electrically conducting cone, where As, At and Am are amplitudes while, αs, αt and αm are phase angles .τw= sign indicates source and (–) sign indicates the sink), respectively. In these figures, it is shown that the velocity component U and the temperature variable (θ) is increased as the values of the source parameter (+δ) is increased and these components are reduced for the sink parameter (−δ). It is also shown the transverse component of magnetic field (ϕ) is reduced for the source parameter (+δ) but on the other hand it is slightly increased for the increasing values of sink parameter (−δ). It is pertinent to point out that the solid lines in each plot is seen the effects of source parameter while the dashed lines highlights the effects of sink parameter. The phenomena in U, temperature variable (θ) and transverse magnetic field variable (ϕ) in the simultaneous presence of source and sink parameter (δ = ±0.6). It is concluded that the increase in Prandtl number Pr is reduced the velocity component U and the temperature variable (θ) in both cases that is source and sink while the transverse component of magnetic (ϕ) is increased in both source and sink regions. The effects of the mixed convection parameter λ on the velocity component, temperature variable and transverse magnetic field are reflected in δ = ±0.7 respectively. In these plots, it can be seen for increasing values of mixed convection parameter λ the velocity component U is increased and variable temperature and transverse magnetic field are reduced with the same trend simultaneously both for source and sink parameter (δ = ±0.7). U, temperature variable (θ) and transverse magnetic field (ϕ) for δ = ±0.9 respectively. It is observed that imposition of porous medium parameter increases the velocity component and decreases the temperature variable (θ) for source parameter and the transverse magnetic field is reduced for sink parameter (−δ) and no changes are observed for the case of source parameter (+δ).δ on the periodical skin friction, heat transfer and current density is presented in Qo is increase and kinetic motion of the fluid particle is decreased. In these plots it is very clear that amplitude of periodic skin friction is increased for increasing values of source parameter δ and is reduced in the sink ranges. In the case of periodical heat transfer this trend is reversed, the amplitude of periodic heat transfer is increased in the sink range and reduced in the source range. It is important to point out that the periodical current density is uniform in both rages. The behavior of periodical skin friction, heat transfer and current density is highlighted in γ in source and sink range respectively. From these figures it is depicted that the amplitude of periodic skin friction is increased for source range and is reduced for sink range, but the periodic heat transfer is increased in sink region and is uniformly distributed in each range. In γ and particularly uniformly distributed in source and sink range. The physical reasoning depicted in γ the magnetic diffusion rate is dominant over viscous diffusion rate. In λ the amount of periodic skin friction is increased in the heat source range while the reverse trend is noted in the case of periodic heat transfer, mean to say the heat sink is significantly dominated. It is important to define that the mixed convection parameter is the ratio of the buoyancy force to flow shear force. The mechanism predicted in λ that buoyancy force is dominant over flow hear force.The influence of the source and sink parameter ±In this paper, the occurrence of periodic/oscillatory convection flow along the surface of electrically conducting cone has been investigated numerically. For this purpose, comprehensive numerical solutions have been obtained to delineate the effect of different parameters involved in the flow model on velocity, temperature field and transverse magnetic field along with periodic skin friction, heat transfer and current density. Characteristics of the transient periodic/oscillatory convection appear largely in skin friction and heat transfer and in some cases of periodic current density. The main objective of this study is to investigate the impact of heat source and sink parameter periodic/oscillatory skin friction, heat transfer and current density.In this study we conclude that intensity of heat and fluid flow is effective in the case of heat source and the heat sink effects are dominated by heat source. Moreover, heat source and sink are not prominent in the case of current density. It is noted that due to domination of the buoyancy force which acts like a pressure gradient the velocity profile, periodic skin friction is increased on the other hand temperature, transverse magnetic field, periodic heat transfer and current density are reduced. Due to the increase of porous medium parameter the avoid space accessible from the surface is increased thus a very significant reduction in periodic skin friction and heat transfer is noted. It is claimed that because of the prevailing attitude of the magnetic diffusion over viscous diffusion the velocity profile, temperature distribution, transverse magnetic field, periodic skin friction, periodic heat transfer, periodic current density are appreciably affected.


Persisting evidence suggests significant socioeconomic and sociodemographic inequalities in access to medical treatment in the UK. Consequently, a systematic review was undertaken to examine these access inequalities in relation to hip replacement surgery. Database searches were performed using MEDLINE, PubMed and Web of Science. Studies with a focus on surgical need, access, provision and outcome were of interest. Inequalities were explored in the context of sociodemographic characteristics, socioeconomic status (SES), geographical location and hospital-related variables. Only studies in the context of the UK were included. Screening of search and extraction of data were performed and 482 articles were identified in the database search, of which 16 were eligible. Eligible studies consisted of eight cross-sectional studies, seven ecological studies and one longitudinal study. Although socioeconomic inequality has somewhat decreased, lower SES patients and ethnic minority patients demonstrate increased surgical needs, reduced access and poor outcomes. Lower SES and Black minority patients were younger and had more comorbidities. Surgical need increased with age. Women had greater surgical need and provision than men. Geographical inequality had reduced in Scotland, but a north-south divide persists in England. Rural areas received greater provision relative to need, despite increased travel for care. In all, access inequalities remain widespread and policy change driven by research is needed. A key tenet of the United Kingdom’s National Health Service (NHS) is that access to healthcare should be fair and equal for all . Whilst A systematic search of published literature was performed on 4th February 2021. The search strategy followed the Population, Phenomena of Interest and Context (PICo) framework , such as shoulder arthroplasty, and studies relating to patients’ postoperative return to work (n = 6). The 16 remaining studies were included in this systematic review.Over the three databases searched , 482 articles were identified, of which 382 were removed in the deduplication process. With duplicates removed, 120 articles were screened against the inclusion criteria. Sixty-six papers published before December 2005 and those without UK-based cohorts were removed. The remaining 54 articles were screened against the exclusion criteria, using full-text copies, resulting in the removal of a further 38 papers. Reasons for removal are shown Figure The 16 studies included in this review are of varying characteristics and demographics. Table The risk of bias checklist for assessing the quality of the included studies is shown in Table p-value from p < 0.001 to p = 0.02. Neuburger et al. [Table r et al.  found thr et al.  found thp < 0.001), socioeconomic inequality did not change significantly. Judge et al. [Table e et al.  reportedp < 0.001). Despite this, by 2007, they reported almost uniformly distributed waiting times across the deprivation quintiles. Cooper et al. [In terms of waiting times, Laudicella et al.  showed tr et al.  was the r et al.  also repr et al.  reportedr et al.  reportedTable p < 0.001; SF-36 mental: p < 0.001). Neuburger et al. [p = 0.04). However, no evidence was found between SES and postoperative morbidity. Clement et al. [p < 0.001). No significant difference between patients’ SES and BMI was found by Clement et al. [p = 0.05 for no association hypothesis) and Jenkins et al. [p = 0.68). Jenkins et al. [Table r et al.  identifir et al.  reportedr et al.  reportedr et al.  reportedr et al. , who shot et al.  also fout et al.  , and a wider socioeconomic gap in provision, measured using SIMD. While provision inequity between socioeconomic groups is still apparent in the UK, evidence shows the gap has fallen over time in England [Scottish geographical inequality in access to hip replacement surgery declined from 1998 to 2008 , however England , 31, 38. England , researcp < 0.001) [p-value was < 0.001. One included study [Increasing numbers of CCGs in the UK have begun implementing rationing measures for smokers and obese patients . Concern< 0.001) . Despite< 0.001) , 39 inve< 0.001) , are not< 0.001) . Neverth< 0.001)  from the< 0.001)  investig< 0.001) ; however< 0.001) . Of the < 0.001) , 33, 39 < 0.001) , 29 failed study  used theed study  change. Only one study had Welsh data and no studies had Northern Irish data. Excluding large samples of the UK population introduces selection bias, as the missing population data may have changed the pattern of inequalities described. Consequently, a narrower approach individually focussing on England or Scotland may have been more suitable. While a lack of research may be responsible for the lack of Welsh and Northern Irish data, it is also possible that geographical search criteria may have been imprecise. A custom UK geographical filter was used for the MEDLINE database search ; it was This review summarises the available literature on access inequalities in hip replacement surgery for the UK. While the heterogeneity of study outcomes and methodology made drawing conclusive evidence challenging, it is clear that access inequality is a major issue in the UK. Potential inequalities in pre-surgical patient consultation were not explored in the included studies. Patient diagnosis and referral to surgery may be impacted by implicit biases present in practitioners, such as an ethnic bias in pain evaluation for Black patients . Despite


Vacuum-assisted breast biopsy (VABB) is a minimally invasive procedure and has become an important treatment method. Although VABB is a minimally invasive procedure, it might cause complications, particularly those associated with blood vessels. In this article, we aimed to describe a 35-year-old female who experienced pseudoaneurysm post-VABB and was successfully treated with embolization. She presented to the hospital with a suspected left breast tumor. The pathology report after biopsy confirmed fibroadenoma, and the patient underwent VABB to remove the tumor. One hour after VABB, the patient described pain and swelling at the location of the removed tumor. Breast ultrasound revealed a hematoma and pseudoaneurysm. The bleeding did not stop following the application of manual compression. Breast hemorrhage was controlled by endovascular embolization. Pseudoaneurysm is an uncommon complication of VABB, and embolization represents an effective method for the management of breast pseudoaneurysm. The introduction of breast cancer screening programs has resulted in the increased detection of benign breast tumors . The defA 35-year-old female underwent a medical check-up due to a painless mass in the left breast, which appeared 2 years prior, without thickening or dimpling of the breast skin, pulling in of the nipple, or bloody nipple discharge. Breast ultrasound revealed a mass at the 3 o´clock position in the left breast, measuring 20mm x 12mm . This maet al. [et al. [et al. [The VABB technique, which was developed in late 1995, uses ultrasound guidance to remove samples of breast tissue through a single, small skin incision . Becauseet al.  reported [et al.  reported [et al. . Followi [et al. . Multipl [et al. .Patients with more than two nodules or nodules with a maximum diameter of 25 mm or larger were found to be associated with a significantly increased risk of hematoma after VABB . HematomThis case represents an incident of failure to stop VABB-induced bleeding using focused compression. Although VABB is a safe procedure, associated with a low rate of typically mild to moderate complications, breast vessel injury is always a risk. Patients who present with increasing pain and rapid growth at the tumor site after biopsy must be evaluated for possible pseudoaneurysm. This patient received a prompt diagnosis and was treated successfully with intravascular embolization.


Du and colleagues  have conFirst, Du et al  note thaall individuals within the EU regardless of citizenship, including refugees and tourists). In other words, the GDPR does not rule out data transfer in principle, but sets high standards [Du et al  are parttandards . This betandards . ArticleSecond, Du et al  offer a More importantly, even if all legal barriers are addressed when adopting such an interface on a global scale, making a contact tracing app mandatory is too bold a proposal. This is not (only) a legal concern, but (even more so) an ethical concern. Morley and colleagues  have synSo, I agree with Du et al  on the n


Prostate cancer is the second most common cancer and the fifth leading cause of cancer-related death among men worldwide . In receChang et al.  reportedWu et al.  evaluateWu et al.  comparedChoi et al.  evaluateMilonas et al.  assessedKimura et al.  performeAbufaraj et al.  performeBRCA1, BRCA2, and ATM germline pathogenic variants are at an increased risk of aggressive disease. They concluded that these rare genetic variants could be incorporated into risk prediction models to improve their precision in identifying males at a higher risk of aggressive prostate cancer and those with newly diagnosed prostate cancer who require urgent treatment.Nguyen-Dumont et al.  performeAndo et al.  reportedIn conclusion, this Special Issue provides updated information on the prognostic factors for non-metastatic prostate cancer after curative therapy, the functional outcomes of local therapy for radiation-recurrent disease, the impact of rare genetic variants on aggressive prostate cancer, and prognostic factors in patients with castration-resistant prostate cancer.


Health Economics Review. 2020; 10 (1), 1–9. It explains the effects of health expenditure on infant mortality in sub-Saharan Africa using a panel data analysis (i.e. random effects) over the year 2000–2015 extracted from the World Bank Development Indicators. The paper is well written and deserve careful attention.This commentary assesses critically the published article in the The main reasons for inaccurate estimates observed in this paper are due to endogeneity issue with random effects panel estimators. It occurs when two or more variables simultaneously affect/cause each other. In this paper, the presence of endogeneity bias  and its omitted variable bias leads to inaccurate estimates and conclusion. Random effects model require strict exogeneity of regressors. Moreover, frequentist/classic estimation (i.e. random effects) relies on sampling size and likelihood of the data in a specified model without considering other kinds of uncertainty.This comment argues future studies on health expenditures versus health outcomes  to use either dynamic panel  to control endogeneity issues among health , GDP per capita, education and health expenditures variables or adopting Bayesian framework to adjust uncertainty  within a range of probability distribution. There is a growing concern of the importance of population health and its contribution to the national economy, but the issue of infant mortality remains a major concern in most of the developing economies including Sub-Sahara Africa , 2. One Health Economics Review, 10 (5) by Kiross et al. [P-values arising from hypothesis tests  with nos et al. , among oview, 10  by Kiross et al.  represens et al.  estimatis et al.  findingsConversely, Kiross et al.  used heaThe endogeneity bias observed in Kiross et al.  paper caIt is also known that countries with similar level of development like sub-Saharan Africa, public health spending differs significantly in health outcomes measures. For example, between 2010 and 2014, the average public health expenditure as percentage of GDP in Tanzania and Zambia was 2.5% and 2.5% respectively . SimilarTo address the aforementioned weakness encountered in Kiross et al. , the useAs a take home message for the readers and reviewers is that, random effects models require strict exogeneity of regressors and in the presence of endogeneity of variables, it leads to inaccurate estimates and misleading conclusion. Further, the Bayesian framework allows the authors to make use of prior knowledge or beliefs about the specific question being studied, as well as the new evidence collected specifically for the study . It alsoFuture studies examining the effects of health expenditures (i.e. public or private) on health outcomes  should either use dynamic system Generalized Methods of Moments (GMM) to control endogeneity and its omitted variables bias or adopting a Bayesian framework that provides a clear picture of parameter uncertainty adjusting for confounding, endogeneity and measurement error within a range of probability distribution .


N = 560), but there was high heterogeneity (96%). Meta‐analysis of two studies found a statistically significant increased number of stools per day in the probiotic group compared to the placebo group at 1 month of age , with moderate heterogeneity (69%). Meta‐analysis of two studies showed no statistical difference in body weight between the two groups  with minimal heterogeneity 23%. Probiotic therapy appears promising for infant regurgitation with some evidence of benefit, but most studies are small and there was relatively high heterogeneity. The use of probiotics could potentially be a noninvasive, safe, cost effective, and preventative positive health strategy for both women and their babies. Further robust, well controlled RCTs examining the effect of probiotics for infant regurgitation are warranted.Infant regurgitation is common during infancy and can cause substantial parental distress. Regurgitation can lead to parental perception that their infant is in pain. Parents often present in general practitioner surgeries, community baby clinics and accident and emergency departments which can lead to financial burden on parents and the health care system. Probiotics are increasingly reported to have therapeutic effects for preventing and treating infant regurgitation. The objective of this systematic review and meta‐analysis was to evaluate the efficacy of probiotic supplementation for the prevention and treatment of infant regurgitation. Literature searches were conducted using MEDLINE, CINAHL, and the Cochrane Central Register of Controlled trials. Only randomised controlled trials (RCTs) were included. A meta‐analysis was performed using the Cochrane Collaboration methodology where possible. Six RCTs examined the prevention or treatment with probiotics on infant regurgitation. A meta‐analysis of three studies showed a statistically significant reduction in regurgitation episodes for the probiotic group compared to the placebo group (mean difference [MD]: −1.79 episodes/day: 95% confidence interval [CI]: −3.30 to −0.27,   Infant regurgitation is common during infancy and can cause substantial parental distress.The currently available evidence does not support or refute the efficacy of probiotics for the prevention and treatment of infant regurgitation but data from the individual trials and subset meta‐analysis of studies are promising.There are no indications from the available data that probiotics have any adverse effects.Further well‐controlled RCTs are warranted to investigate the efficacy of various strains and species, dosage, and combinations of probiotics. The secondary outcomes were the effect of probiotics on gastric emptying time, number of stools, growth rate , admissions to hospital related to infant regurgitation, loss of parent working days related to infant regurgitation, number of admissions of mother to hospital due to anxiety/depression, number of visits to any health professional, and adverse events related to probiotic supplementation (mother and infant).2.2https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal; US National Library of Medicine: clinicaltrials.gov; ISRCTN Registry https://www.isrctn.com/). All potentially relevant titles and abstracts were identified and retrieved during the search. Independent hand searches were undertaken, and the bibliographies of each article were assessed for additional relevant titles.Eligible studies were sought from the Cochrane Central Register of Controlled Trials  in the Cochrane Library; MEDLINE via PubMed (1966 to 9 April 2021); Embase (1980 to 9 April 2021); and CINAHL (1982 to 9 April 2021) using the following subject MeSH headings and text word terms: ‘neonate(s)’, ‘newborn(s)’, ‘infant(s)’, AND ‘regurgitation’ OR ‘infant regurgitation’ OR ‘infantile reflux’ OR ‘reflux’ AND ‘probiotic’. Language restrictions were not applied. We searched clinical trials registries for ongoing or recently completed trials : 2.3We included randomised controlled trials (RCTs) that compared probiotics (any dose or composition) to placebo, control, or other forms of treatment in mothers during the antenatal period, and term and preterm infants in the postnatal period (from birth and up to 12 months) for the prevention (mother/infant) and treatment (infant) of infant regurgitation. Articles in any language were considered if there was an abstract in English.We used the data extraction form available within Review Manager software (RevMan) to extract data on the participants, interventions and control(s), and outcomes of each included trial. Two review authors (JF and KP) screened the title and abstract of all identified studies. The titles were also checked by third author (SF). We reassessed the full text of any potentially eligible reports and excluded the studies that did not meet all the inclusion criteria. Two review authors (JF and KP) independently extracted data from each study without blinding to authorship or journal publication. In case of any disagreement, the three review authors resolved them by discussion until reaching a consensus. One review author (JF) entered data into RevMan, and two review authors (KP and SF) verified them  were used to assess the methodological quality of included trial  were enroled across the six studies.L. paracasei DSM 24733, L. plantarum DSM 24730, L. acidophilus DSM 24735, and L. delbrueckii subsp. bulgaricus DSM 24734, three strains of bifidobacteria , and one strain of Streptococcus thermophilus DSM 24731. The probiotics in this study were given to mothers 4 weeks before the expected delivery date (36th week of pregnancy) until 4 weeks after delivery   from baseline to Day 28 of the study period, but did not provide any summary data. At the end of the second week the difference with the placebo group was significant (p = 0.05) and there was a trend to a significant result reported at the end of the third week of treatment (p = 0.06). Indrio et al. (p < 0.001). Baldassarre et al. .We were unable to include the remaining three studies in the meta‐analysis due to the method of reporting. Garofoli et al.  reportedo et al.  found ine et al.  reportedN = 468, p = 0.00001).Indrio et al.  was the 3.2p < 0.001). Indrio et al. . However, the I2 statistic of equal to 69% indicates moderate heterogeneity . Garofoli et al. .Only one study reported no. of stools/day after 3 months' administration of the probiotic/placebo. Indrio et al.  and foun3.4I2 = 23%, N = 112, p = 0.28] .Four studies reported on total body weight after 1 months' administration of the probiotic/placebo. Two studies were able to be included in the meta‐analysis  and control group , p = 0.087 at 4 weeks after commencing treatment. However, when calculating summary data, we found a significant different between the two groups  and this was checked and supported by our statistician.Garofoli et al.  reportedF = 118.95, p < 0.001; treatment effect: F = 0.01, p = 0.92; interaction effect: F = 1.43, p = 0.24).Baldassarre et al.  reportedSD: 1.21) and placebo groups , p = 0.108 at 4 weeks.Garofoli et al.  reported3.5N = 468, p = 0.00001). Indrio et al. . Indrio et al. .Only one study , however, we repeated this analysis and found a significant difference between probiotics and the control group (p = 0.0009). Garofoli et al. (p = 0.087), however, we calculated the summary data and found there to be a significant difference between the probiotic and control groups (p = 0.003). All studies reported on adverse events.The remaining four studies were rated unclear risk of reporting bias. We were not able to locate a trial registration record for Indrio et al. , 2008, ao et al.  reportedi et al.  reported3.8.7We considered the five studies that were supported by the manufacturer of the intervention to be at high risk of bias (Baldassarre et al., 4To our knowledge, we report the first systematic review to investigate the efficacy of probiotic supplementation for the prevention and treatment of infant regurgitation. It involved a rigorous review process with adherence to internationally recognised Cochrane and Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines. We found six RCTs on the use of probiotics for the prevention or treatment of infant regurgitation for inclusion in the systematic review.L. reuteri DSM 17938 (Indrio et al., L. reuteri ATCC 55730 (Indrio et al., Meta‐analysis of three of the six trials showed a statistically significant reduction in regurgitation in the infants receiving L. reuteri is also found to exhibit antimicrobial activity, producing reuterin, a broad‐spectrum antibacterial substance (Axelsson et al., L. reuteri strains act through diverse mechanisms.The remaining individual studies also reported a statistical reduction in episodes of regurgitation with the use of probiotics (Garofoli et al., L. reuteri ATCC 55730 and L. reuteri DSM 17938 found a statistically significant increase in the number of stool evacuations and it has reported that probiotics could play a crucial role in the modulation of intestinal inflammation that may contribute to infant regurgitation (Indrio et al., Individual studies found that gastric emptying was statistically significantly faster in the infants receiving probiotics compared with placebo. It has been reported that probiotics improve gut motility and gastric emptying time and thus reduces gastric distension and visceral pain (Garofoli et al., The impact of infant immaturity, disturbance of the microbiome through caesarean section and maternal mental health has been recently considered. A mixed methods study examined greater than 1 million admissions of infants in NSW, Australia to hospitals in the first year following birth (Dahlen et al., None of the included studies in this systematic review reported on admissions to hospital due to maternal anxiety/depression. The study by Dahlen et al.  also fouL. reuteri DSM 17938 or its original strain, L. reuteri ATCC 55730 (Garofoli et al., L. reuteri administration: increased gastric emptying and reduction in crying time, regurgitation episodes, constipation, and fasting antral area. The authors based their findings on changes in intestinal microbiota, improved mucosal barrier, anti‐inflammation, improved motility of the whole intestine and neuroimmune interaction. However, other strains of probiotics could also perform such actions.Of the six studies included in the review, five administered 4.1We thoroughly reviewed the studies for results and assessed their risks of bias. There was an overall low risk of bias in the trials for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment and incomplete outcome data. There was an overall high risk or unclear risk of selective reporting bias and five of the six trials reported receiving financial support from the manufacturer or the makers of the probiotic used Figure .5The currently available evidence does not support or refute the efficacy of probiotics for the prevention and treatment of infant regurgitation. However, data from the individual trials and subset meta‐analysis of studies measuring the effect of probiotics are promising. There are no indications from the available data that probiotics have any adverse effects. The use of probiotics could potentially be a noninvasive, safe, cost effective and preventative positive health management strategy for both women and their babies. Further well‐controlled RCTs are warranted to investigate the efficacy of various strains and species, dosage, and combinations of probiotics to determine the most effective for preventing and treating infant regurgitation. In addition, further research is required to determine the effectiveness of administering probiotics to women antenatally and/or postnatally to prevent regurgitation in breastfed infants and their effect on maternal mental health.This project was supported by the School of Nursing and Midwifery, Western Sydney University.The authors declare no conflict of interests.Jann P. Foster, Charlene Thornton, and Hannah G. Dahlen conceived the research project and coordinated the contributors. Jann P. Foster and Kim Psaila developed the search strategy and searched the databases. Jann P. Foster, Kim Psaila, and Hannah G. Dahlen participated in the study selection. Jann P. Foster, Kim Psaila, and Hannah G. Dahlen performed the data extraction. Jann P. Foster, Kim Psaila, Hannah G. Dahlen, and Sabina Fijan interpreted the findings. Jann P. Foster, Hannah G. Dahlen, Kim Psaila, and Sabina Fijan wrote the first draft of the results and Nadia Badawi, Virginia Schmied, Charlene Thornton, and Caroline Smith revised subsequent drafts. Jann P. Foster, Hannah G. Dahlen, Kim Psaila, and Sabina Fijan prepared the manuscript and revised every version of the manuscript. Nadia Badawi, Virginia Schmied, Charlene Thornton, and Caroline Smith contributed to the revision of the manuscript.


It is now more than 90 years since Irving Langmuir used the technical term “plasma” to describe an ionized gas . Plasma International Journal of Molecular Sciences, includes 14 original articles and 3 reviews providing new insights into the application and molecular mechanisms of plasma biology.On the basis of the background outlined above, this Special Issue entitled, “Plasma Biology”, of The solutions treated with plasma are referred to as “plasma-activated medium (PAM)” , plasma-N-acetylcysteine was found to prevent PAM/TRAIL-induced cancer cell apoptosis, suggesting that ROS is related to the induction of PAM/TRAIL-mediated apoptosis.Hwang et al.  examinedTerefinko et al.  demonstrDickeya solani and Pectobacterium atrosepticum, which are important plant pathogens. Moreover, the mechanism of action of PAL was possibly due to the presence of ROS and RNS.Dzimitrowicz et al.  reported2O2). The model can be used to quantify the selective and synergistic anticancer effect of PTL in both susceptible and resistant cells.Bengtson and Bogaerts  developeIn a report by Bekeschus et al. , human mZimmermann et al.  demonstrCandida albicans with a sublethal dose of CAP. Subsequent analysis of the CAP treated yeast identified six single-nucleotide variants, six insertions, and five deletions, as well as the decreased or increased activity of the corresponding enzymes.Tyczkowska-Sieroń et al.  treated Haralambiev et al.  examinedEscherichia coli, with or without a plasmid that includes an ampicillin resistance gene and chloramphenicol acetyltransferase (CAT) gene, were treated with a dielectric barrier discharge (DBD) plasma torch. The plasma treatment was found to degrade the lipopolysaccharide (LPS) and DNA of the bacteria as well as CAT. Furthermore, the plasma treatment was equally effective against antibiotic-resistant and non-resistant bacteria. This finding suggests that plasma treatment is effective against bacterial strains resistant to conventional antibiotic therapy.Sakudo et al.  investigKwon et al. studied the attachment of human mesenchymal stem cells (hMSCs) to the surface of titanium modified by plasma treatment generated using either nitrogen (N-P), air (A-P), or humidified ammonia (NA-P) . N-P, A-Przekora et al.  producedHan et al.  performeAdhikari et al.  examinedSun et al.  used higA review by Zubor et al.  focuses A review by Chokradjaroen et al.  providesA review by Braný et al.  gives anInternational Journal of Molecular Sciences, which highlights the research of eminent scientists in the field of plasma biology. The Editors would like to thank all the contributors to this Special Issue for their commitment and enthusiasm during the compilation of the respective articles. The Editors also wish to thank Kaitlyn Wu and other members of the editorial staff at Multidisciplinary Digital Publishing Institute (MDPI) for their professionalism and dedication. Hopefully, readers will enjoy this Special Issue and be inspired with new ideas for future research.Finally, the Editors are delighted to have had the honor of organizing this Special Issue for


Mycerobas carnipes was sequenced in this study and the total length is 16,806 bp containing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and one control region. The phylogenetic analysis based on 13 PCGs of five grosbeaks and other Fringillidae birds demonstrated that Mycerobas, Coccothraustes, and Eophona had close phylogenetic relationships for clustering as three sister branches, and supported that Eophona originated earlier in phylogeny.The complete mitochondrial genome of  Mycerobas carnipes is a grosbeak in the family Fringillidae, whose ecological habitats often occur in forest and shrubland and which distributes in northeastern Iran, the Himalayas to the western Ten-zan, central and southwest China  perform differently using the Bayesian inference (BI), the maximum-likelihood (ML) criteria, and different types of datasets. This study presents the complete mitochondrial genome of M. carnipes and constructs a phylogenetic tree based on 13 PCGs of five grosbeaks and other Fringillidae birds for better understanding relationships of grosbeak genera.t et al.  and the t et al.  based ont et al.  and Yangt et al.  based ona et al.  based ona et al.  based ona et al. , the topM. carnipes, which died of airport protection facility for bird strikes in the Ganzi Gesser Airport, Sichuan Province, China . The specimen was stored in the Natural Museum of Sichuan University with a voucher number of QZKK091. The complete mitochondrial genome of M. carnipes was sequenced by Chain Termination Method and the genome sequence has been deposited in the GenBank with the accession MW 304000. The assembly of mitochondrial genome was finished via SeqMan software (version 7.1.0), and the annotation was generated by MITOS first (Bernt et al. The total mitochondrial DNA was extracted from the muscle tissue of M. carnipes and other 11 Fringillidae species were used for phylogenetic analysis by BI and ML method (Carpodacus, Loxia, and Chloris; and the lineage formed three branches with Eophona basal to them. The phylogenetic result supported that Eophona had earlier origin than other grosbeaks which was different from previous studies with one or a minority of genes (Arnaiz-Villena et al. The mitochondrial genome sequence of 13 PCGs of L method . The ML L method . A discrL method  with simL method  accordin


We estimated life expectancy from detailed zoo records for 133 818 individuals across 244 parrot species. Using a principled Bayesian approach that addresses data uncertainty and imputation of missing values, we found a consistent correlation between relative brain size and life expectancy in parrots. This correlation was best explained by a direct effect of relative brain size. Notably, we found no effects of developmental time, clutch size or age at first reproduction. Our results suggest that selection for enhanced cognitive abilities in parrots has in turn promoted longer lifespans.Previous studies have demonstrated a correlation between longevity and brain size in a variety of taxa. Little research has been devoted to understanding this link in parrots; yet parrots are well-known for both their exceptionally long lives and cognitive complexity. We employed a large-scale comparative analysis that investigated the influence of brain size and life-history variables on longevity in parrots. Specifically, we addressed two hypotheses for evolutionary drivers of longevity: the  Howevcognitive buffer hypothesis posits that increased cognitive flexibility enabled by a relatively larger brain allows species to solve problems that would otherwise increase their extrinsic mortality, hence allowing for increased longevity [expensive brain hypothesis argues that there is an indirect association between brains and longevity, with an investment in expensive brain tissue slowing down the pace of life through increased developmental time and increased parental investment per offspring [delayed benefits hypothesis extends the expensive brain hypothesis and reverses the directionality of its argument, positing that a shift to a higher quality, skill-based diet lowered adult mortality rates and supported a longer juvenile period that facilitated inter-generational skill transmission. This extended development in turn allows for investment in brain growth that further promotes skill-based foraging niches. In other words, long-lived, extractive foraging species evolve larger brains because they can benefit most from learning [et al. [et al. [Three non-mutually exclusive hypotheses have been proposed to explain the correlated evolution of larger brains and longer lifespans. First, the ongevity . Second,ffspring . Third, learning . Previoulearning ,16. For  [et al.  showed t [et al.  showed bPsittaciformes) are famous for both their long lives and complex cognition [Micropsitta keiensis, 12 g) to kakapo  [et al. [et al. [Parrots  . In the  3000 g)  used max [et al. , finding [et al.  found thet al. [et al. [One of the greatest challenges for comparative life-history studies is sourcing good quality data . For inset al. ) and som [et al. ). Maximu [et al. . For spe [et al. . It calc [et al. ,33. Base [et al. . We addicognitive buffer hypothesis predicts a direct effect of relative brain size on life expectancy, with larger brained species living longer [expensive brain hypothesis predicts that the effect of brain size on life expectancy is indirect, emerging from increased developmental time and parental investment per offspring [delayed benefits hypothesis would also predict a direct relationship between relative brain size and longevity [Psittaciformes to date and contributes to a broader understanding of this understudied group.Here, we present a phylogenetic comparative analysis focused on brain size and its effects on longevity in parrots. First, we estimate life expectancy from Species360's zoological information management system (ZIMS) with records of 133 818 individuals across 244 parrot species. We then test for a correlation between life expectancy and relative brain size after removing the effect of covariates. Third, we used a DAG to distinguish between two possible pathways for this correlation. The g longer , while tongevity , it woul. 2 (a)We obtained data on birth and death dates from Species360's ZIMS. After cleaning  we included records for 133 818 individuals across 244 species. To estimate life expectancy, we implemented Bayesian survival trajectory analysis , which a0 and a1), age independent (adult) mortality (c) as well as senescent mortality . Cumulative survival can be calculated aswhere Life expectancy at birth is calculated asWe used the Gelman–Rubin statistic  to dete (b)et al. [et al. [et al. [We collected body mass data from ZIMS. Additional body mass measurements were included from the literature if no captive records were available for a species . We thenet al. , from Sc [et al.  and from [et al. , and sim [et al. , insular [et al. , maximum [et al. , clutch  [et al. , develop [et al. . Diet, iet al. [We used a DAG  to decidet al. .Figure  (c)et al. [To test for a correlation between life expectancy and relative brain size, we first constructed a Bayesian structural equation model (model 1) with life expectancy as the main variable to be explained by relative brain size and four other potential covariates. We included a total of 360 species for which at least one variable was known. The structure of this first model was as follows: LE ∼ I + BO + RB + LA + D, where: LE, standardized log life expectancy; I, insularity (binary); BO, standardized log body mass; RB, relative brain size; LA, standardized maximum latitude range and D, protein content diet . Relative brain size was calculated as: BR – pBR, where: BR, standardized log brain mass and pBR, predicted brain mass from a second model that ran simultaneously: pBR∼BO. Relative brain size has been shown to correlate with innovation rates in birds , and we et al. , using tTo test whether any correlation between relative brain size and longevity could be indirectly caused by developmental time, delayed juvenile periods and/or parental investment, we ran a second model (model 2) where developmental time (incubation period plus fledging period in model 2) and clutch size were included as additional covariates. Both variables were log transformed and standardized. Because data on AFR  were only available for 89 species and the available data were biased towards later AFR , we did not attempt to impute this variable but tested its effect in a third model (model 3) limited to cases where AFR was known.cognitive buffer hypothesis), we would expect the coefficient of the brain size effect to be positive and similar in all three models. If an increase in relative brain size only causes an increase in developmental time (expensive brain hypothesis), we would expect the coefficient of the brain size effect to be positive in model 1 and zero in models 2 and 3. We would also expect an effect of developmental variables in models 2 and 3.To assess which hypothesis was best supported by the data, we compared the effect of relative brain size in the three models. If an increase in relative brain size directly causes an increase in life expectancy ; however, covariance was generally low between species that belonged to different genera (c).Overall, we were able to estimate life expectancy for 217 species of 244 species for which we had data . This included representatives of all eight major genera (i.e. those with at least 10 species) and over half of the extant parrot species. The shortest-lived genera were the small-bodied t genera c.Figurec for model 2; electronic supplementary material, results for models 1 and 3). Relative brain size also had a small, but consistently positive, effect on life expectancy . In particular, model 2 showed no effect of developmental time  or clutch size  on longevity, and there was no clear effect of AFR on longevity in model 3 . However, it should be noted that these models were designed to test the effect of relative brain size, so other parameter estimates should be interpreted with caution [Model 1  as well as models 2 and 3  had similar estimates for the direct effect of relative brain size. As expected, body size was strongly and positively correlated with life expectancy  uncertainty about variable estimates; (ii) imputation of missing values; (iii) a principled representation of relative brain size; and (iv) phylogenetic signal. We believe this method has some major advantages. Most notably, we could estimate both life expectancy and its uncertainty in each species. This allowed us to fully exploit the fact that we have a hundred-fold more data for some species, instead of relying on a single-point estimate of maximum longevity as in previous studies of longevity in parrots ,27. We aPsittaculirostris and Charmosyna which have been historically difficult to manage in captivity. We dealt with this by excluding potentially problematic species from the initial life expectancy estimations, and instead imputed values in the final model . We can still not be completely sure that the patterns observed in the data are all representative of the evolutionary processes that shaped them, but it is highly unlikely that the clear positive correlation between relative brain size and life expectancy is owing to captivity. It could even be expected that large-brained species live shorter in captivity, because of the higher metabolic rates required to keep the large brain supplied with glucose. This has been shown to be the case within species in captive guppies [Our study also departs from most previous studies of longevity by using data from captivity on life expectancy ,55–57. T guppies . Since s. 5cognitive buffer hypothesis, suggesting that relatively large brains may have buffered parrots against environmental variability and/or predation threats reducing sources of extrinsic mortality and allowing longer lifespans. This result is consistent with previous studies in other birds, suggesting that common processes may explain longevity in altricial birds. In addition to their longevity, parrots are famous for their complex cognition. It remains largely unknown what evolutionary processes have driven cognitive evolution in parrots, but given the results of our study, in addition to those of Munshi-South & Wilkinson [Overall, our results are consistent with the ilkinson , future ilkinson , showingClick here for additional data file.


Optical humidity sensors have evolved through decades of research and development, constantly adapting to new demands and challenges. The continuous growth is supported by the emergence of a variety of optical fibers and functional materials, in addition to the adaptation of different sensing mechanisms and optical techniques. This review attempts to cover the majority of optical humidity sensors reported to date, highlight trends in design and performance, and discuss the challenges of different applications. The measurement of relative humidity (RH) is an important part of heating, ventilation, air conditioning, and refrigeration (HVACR), which provides quality control in numerous aspects of daily life. The full range of applications include: (a) manufacturing ; (b) refrigeration ; (c) packaging ; (d) transportation ; (e) building conditioning ; and (f) healthcare ; (g) agriculture/forestry ; (h) touchless control systems ; (i) weather stations ; hence, an accurate and reliable means to monitor RH supports the development and operation of numerous industries, potentially connected together under the internet of things (IoT).Owing to different environments and requirements, a wide variety of humidity-sensing technologies  have been researched and developed in the literature, including optical/photonic/optoelectronic ,2,3, quaOptical humidity sensors include colorimetric indicators, control systems, point sensors, and distributed sensors. Among point sensors, the most common types involve gratings and absorption loss , with eaRelative humidity (RH) indicates the percentage of water vapor in a water-air mixture relative to the saturation level  at a given temperature. Hence, at a lower temperature, 100%RH can be achieved with fewer water molecules. This effect can be observed with the common phenomenon of condensation on cooler surfaces. For simple testing of a humidity sensor, the amount of water molecules is varied instead of the temperature. This is because changing the temperature could lead to unwanted temperature-related effects, including thermo-optic, stress-optic, and thermal expansion.A humidity sensor is defined as a device that provides a measure of the RH and either presents the information directly to the user or serves as an actuator to drive the next stage in a larger system, as illustrated in Low-cost functional strips providing a means to assess the approximate level of RH by eye are useful for electronics, greenhouses, and patient monitoring. Typically, accuracy and response time are not prioritized, as the checks are performed manually. On the contrary, color uniformity and dynamic range are considered important for the end-users. Two or more colorimetric strips of different color maps can be used in conjunction to improve the accuracy of readings.The demand for a readily accessible humidity indicator that is vibration resistant likely peaked during World War II, when people became concerned about the poor condition of weapons and ammunition. High levels of humidity combined with poor packaging methods led to corrosion and moisture damage. In the beginning, the concept for the first color-change humidity indicator involved a simple go/no-go method of measuring humidity. In the late 1940s, RHs in the range of 30%RH–35%RH were considered important because it is the onset for corrosion . For theAmong the earliest humidity-sensitive colorimetric indicators was one reported by Tian et al. in 2008  Figure . The tea2-based photonic crystal material. A 40 nm spectral shift was demonstrated by varying the RH, and a 1%RH was claimed to be visually distinguishable. The colorimetric indicator was fabricated on silica glass using glancing angle deposition (GLAD). The color mechanism is also based on Bragg resonance. Hong Chi et al. [Matthew M. Hawkeye et al.  developei et al.  used a dAndrew Mills et al.  reportedConventional touchless control inputs are either based on voice , motion , or capacitance . Such controls enable the non-contact operation of gadgets, machinery, or infrastructure, which has the benefits of convenience and hygiene. While these technologies work fine most of the time, false inputs are a possibility. With voice input, background noise can sometimes interfere and become misinterpreted as valid commands. Motion commands can be erroneously entered if the foreground contains multiple moving objects or people. Even with capacitance-based controls, static charge and liquid droplets can hinder the ability of the system to distinguish user inputs from random perturbations. On the other hand, humidity-based control can be more reliable, though possibly limited in variety. The humidity signal can be generated by human breath or finger proximity, and changes are much faster than that of the ambient environment, which lends itself to easy recognition.2, nanosheets that respond to humidity with changes in potentially spatially resolvable color  and electrical resistance. A variation of 0–320 kΩ was observed for the full RH range. The response time is 30 s, which limits the applications to those with slow-moving inputs. The VS2 nanosheet coating was first prepared in solution with a modified liquid-exfoliation method and then transferred to a polyethylene terephthalate (PET) substrate with a higher surface energy for suitable adhesion force. The operating principle involves moisture interaction with the interval structures of the nanosheet, as well as the dynamics of exposed metal atoms, which influences its electrical resistance.In 2011, Jinish Mathew et al.  demonstr3Sb3P2O14 and the proton exchanged phosphatoantimonic acid H3Sb3P2O14 were synthesized by a conventional solid-state reaction followed by ion exchange with HNO3. Dropcasting the resulting suspension onto a quartz substrate leads to randomly overlapping, c-oriented nanosheets. The coating absorbs water vapor and swells in thickness, resulting in a change in resonance condition and thus a shift in Bragg wavelength . Li Yu et al. [Katalin Szendrei et al.  Figure  also devu et al.  developePoint humidity sensors provide a single spatial reading of RH and are the most common type due to their simplicity, high sensitivity, and relatively low cost. Some humidity sensors feature a single-ended detection method, where the sensor head is a probe, which is useful for measuring confined environments. Point humidity sensors come in a huge variety of forms and sensing mechanisms, which makes comparing the sensitivities meaningless when the units are different. Instead, the limit of detection (LOD) is compared, which also takes into account the electro-optic devices used for signal conversion.The earliest optical-based point humidity sensors were reported in the 1980s. Hermann Posch et al.  showed t304-based thin-film colorimetric indicator that can be interrogated by electro-optics. The response time is 1 min, and the sensitivity is 4.9 × 10−5 dB/%RH (400 nm wavelength) between 10%RH and 90%RH. Co304 films were fabricated by pyrolysis of a thin layer of cobalt 2-ethylhexanoate, which was then spin-coated on a glass substrate from a mixed solution of toluene and 1-butanol. The film reacts to different RH due to the water-induced absorption of the probe light.Yoshihiko Sadaoka et al.  demonstrA fiber-optic humidity sensor was developed by Francisco J. Arregui et al.  Figure , which c−6 a.u./%RH between 10%RH and 90%RH. The polyimide coating is hydrophilic and thus swells in humid environments as the water molecules migrate into the polymer. The overlap between the evanescent waves of light and the water molecules within the polymer gives rise to attenuation of light, providing an indication of the RH level.Francisco Arregui et al.  used an 2. The sensitivity with respect to RH is very irregular between 3%RH and 90%RH, while the response time is in the order of seconds. Prior to coating, the optical fiber was stripped of its cladding and annealed to conform to a U-bend probe. The sensing section was then functionalized with the aqueous solution of PVA and CoCl2 before being left to dry. The coating swells with increasing RH and bends the fiber, thus attenuating the light through bend-induced optical leakage. Ainhoa Gaston et al. [A plastic optical fiber (POF)-based humidity sensor was developed by Rajeev Jindal et al. , with thn et al.  reportedShinzo Muto et al.  Figure  exploite2 film overlay on side-polished optical fibers was presented by Alberto Alvarez-Herrero et al. [2 film was deposited via electron-beam evaporation on a side-polished fiber held in a groove. Water molecules in the film change the coupling conditions between light propagating in the fiber and the substrate. The sensor works by monitoring the shift in resonant wavelength as a function of RH. Lina Xu et al. [A highly sensitive humidity sensor using a TiOo et al. . The LODu et al.   and PSS coating was demonstrated by C. R. Zamarreño et al. [2/PSS onto an MMF, facilitating a porous structure with a thickness comparable to that of the wavelength of the probe light. Upon absorbing water molecules, the change in the coating thickness and its refractive index leads to a change in the lossy resonance conditions, which shifts the resonance peaks to longer wavelengths. Matthew M. Hawkeye et al. [2 fabricated by using glancing angle deposition (GLAD). The LOD can be as low as 1%H with a dynamic range of 3–90%RH. The GLAD process enabled the fabrication of complex photonic crystal devices through a single step and was used in this work to coat a silicon or glass substrate with TiO2. As RH increases, water vapor penetrates the porous structure and condenses within the photonic crystal. As a result, the refractive index and optical path length increase. Both underlying effects are modified as a result, which is the Bragg resonance , and the FPI resonances  are shifted to longer wavelengths.Lossy mode resonance (LMR) with titanium dioxide  methacrylate (PEGMA), and cross-linker poly(ethylene glycol) diacrylate (PEGDA). The precuring mixture was sandwiched between a cover glass and a fluorinated glass slide, positioned above a NdFeB magnet and below a strong UV light source for photo-polymerization.Ming-Yue Fu et al.  reportedWei Chang Wong et al.  reportedA fiber-bend-based approach was taken by Jinesh Mathew et al.  Figure , where aLi Han Chen et al.  applied 2 nanoparticles were immobilized into a nanostructured sol-gel matrix and incorporated onto a cladding-removed optical fiber via dip coating. Absorption spectroscopy reveals the correlation between output power and RH.A Boehmite nanorod and gold nanoparticle nanocomposite film was used by Priyank Mohan et al.  for locaSandra F. H. Correia et al.  Figure  reportedTao Li et al.  developeYanjuan Liu et al.  introducGinu Rajan et al.  etched aJinesh Mathew et al.  studied A hybrid union of FBG and reflection-mode PCF interferometer was proposed and implemented by Jinesh Mathew et al.  for simuLourdes Alwis et al.  evaluateA no-core fiber structure was adopted by Li Xia et al. , with a P. Sanchez et al.  Figure  explored2O3+) and poly-sodium 4-styrenesulfonate (PSS−), which is used for selective adsorption. Yinping Miao et al. [A combination of interior-coated PCF with LPFG was reported by Shijie Zheng et al. . The seno et al.  exploiteYun Cheng et al.  demonstrM. Batumalay et al.  applied 3 gel was deposited on an isosceles prism and annealed to form the functional coating. The coating responds to moisture in the air by changing its refractive index with the intake of water molecules. The reflected optical power was collected to provide a readout of the RH. Branislav Korenko et al. [Iron titanium oxide was tested for humidity-sensitive properties by Nidhi Verma et al. . The dyno et al.  created 2O3 film. The LOD is 0.65%RH, and the response time is 18 min. The sensitivity is 310 pm/%RH between 20%RH and 90%RH, and the dynamic range is 20%RH–90%RH. Porous anodic alumina (PAA) was fabricated starting from high purity aluminum, which was electrochemically polished and anodized before removal in phosphoric acid. The PAA was attached to the tip of an optical fiber using adhesive. The micro-pores readily absorb water molecules due to the capillary condensation effect, albeit they are easily saturated at higher RH. The change in the effective refractive index in the etalon produces a shift in the resonance spectrum as a function of RH. Z. Harith et al. [Chujia Huang et al.  developeh et al.  comparedAn intensity-based humidity sensor was conceived by Zhi Feng Zhang et al.  Figure , which uAitor Urrutia et al.  performeGetinet Woyessa et al.  reported2 produces the LMR, whose effective refractive index is sensitive to RH. A microfiber knot resonator with a PVA overlay was developed by Jong Cheol Shin et al. [2 substrate, the PVA overlay was deposited using the spin-coating technique. The microfiber allows a significant portion of the evanescent field to interact with the PVA. The PVA coating changes its refractive index with varying RH and thus alters the effective refractive index seen by the guided mode(s). Such changes affect the resonant wavelength, which can be tracked as a function of RH.J. Ascorbe et al.  Figure  worked on et al. . The sen2 to create a differential humidity sensor based on two different polymer waveguides. The response time is 700 ms. The sensitivity is 0.47 dB/%RH between 40%RH and 90%RH, and the dynamic range is 35%RH–98%RH. The GO was fabricated using a variant of Hummer’s method, which used deionized water as the solvent. TiO2 nanoparticles were synthesized in ethanol. Two SU8 polymer waveguides were fabricated on a SiO2 substrate, each with two layers being undercladding  and core layer . Fiber arrays were aligned to the channels for integration. The two different coatings were drop-casted onto the two waveguides and UV cured. In terms of operation, increasing RH leads to an increase in coating refractive index of the TiO2-coated waveguide, which reduces optical confinement and increases water-absorption-induced optical loss at the interface. The opposite effects occur for the graphene-oxide-coated waveguide due to increasing interlayer distance with increasing RH. The output signal is taken from the difference between the waveguide transmissions to obtain the maximum possible sensitivity.Lu Shili et al.  reportedA GO PVA composite film was developed by Youqing Wang et al. , which i2 alcohol suspension is treated by ultrasonication before being dropped into a basin containing the side-polished fiber. As the RH increases, more water molecules are adsorbed on the WS2 layer with moderate adsorption energies and a moderate degree of charge transfer. Larger amounts of electrons are transferred from WS2 to H2O, which reduces the conductivity and light absorption. As a result, the transmission of the fiber is proportional to the RH. George Y. Chen et al. [Yunhan Luo et al.  side-poln et al.  exploiteA lithium chloride film coated on the end-face of an optical fiber was used by Bao-Kai Zhang et al.  to quantTapered fiber coated with multiwalled carbon nanotubes slurry was explored by Habibah Mohamed et al.  Figure . The LODJia Shi et al.  incorpor2 and TiO2 nanoparticles were deposited from stable colloidal precursor suspensions to create the first multilayer. Subsequently, a suspension of H3Sb3P2O14 exfoliated nanosheets humidity-responsive optical cavity was spin-casted onto it to form the optical cavity. Then, a monolayer of light-emitting polystyrene nanospheres was deposited and covered by a new layer of H3Sb3P2O14. Swelling of the nanosheet layer by increasing the RH shifts the spatial and spectral positions of the optical cavity resonances relative to those of the emission band of the dyes. The result is either a fluorescent turn-off or a turn-on effect with changing RH. Weijia Wang et al. [A fluorescent resonator humidity sensor was developed by Katalin Szendrei et al.  based ong et al.  introducYung-Da Chiu et al.  Figure  investigA cascaded peanut-shaped structure coated with PVA was proposed by Zhaowei Wang et al. . The aimBo Wang et al.  construcAn HCF with a polyimide film was used as a humidity sensor by Ce Bian et al. . The resHamid E Limodehi et al.  created Kasun Prabuddha Wasantha Dissanayake et al.  presenteAg-decorated ZnO nanorods have been exploited by Shweta Jagtap et al.  with a fPoonam D. Mahapure et al.  studied Yu Shao et al.  tested aA two-mode microfiber knot resonator coated with reduced GO was designed and fabricated by Le . The LODChunhua Tan et al.  exploredAnother Fabry-Perot-based humidity sensor was developed by Jinze Li et al. . It invo2Cl2 with ultraviolet laser irradiation. The irradiation power was optimized to produce the best morphological results on the TPPS thin film attached to the fiber end-face. Reflection spectroscopy was applied to analyze the local environment. Both the refractive index and absorption coefficient depend on the environmental humidity. The thin film also exhibits low-quality factor random Fabry-Pérot interference patterns. Miguel Hernaez et al. [2 film to facilitate LMR absorption bands. Poly(ethyleneimine) (PEI) solution in deionized water and GO powder were used for the layer-by-layer assembly of the sensitive layer on top of the SnO2 underlayer. The refractive index of the PEI/GO coating is sensitive to changes in RH, which results in wavelength shifts of the LMR band.Mahboubeh Dehghani Sanij et al.  exploredz et al.  reportedA nanocomposite film was presented by Mingyu Chen et al.  Figure , which oRang Chu et al.  reportedAneez Syuhada et al.  fabricatDeyhaa A. Resen et al.  proposedHumidity-dependent plasmonic coupling within a 2D network of gold nanoparticles was exploited by Marco A. Squillaci et al. . The res2) or tungsten disulfide (WS2). Only the Ti/MoS2 showed a response when changing the RH from 58% to 88%. Hence, MoS2 exhibits higher sensitivity on Ti with 36-nm thickness compared with that of WS2.N. Kaur Sidhu et al.  carried Susana Novais et al.  dip-coatAnand M. Shrivastav et al.  construc2 coating. Increasing RH decreases the RI of the SnO2 thin film, which reduces the reflectance of the fiber tip end-face and thus decreases the visibility of the interference fringes. The sensitivity is 39.49 × 10−3%/RH between 40%RH and 90%RH, and the dynamic range is 40%RH–90%RH.Ce Bian et al.  publisheNiobium disulfide (NbS2) was explored by Enze Zhang et al.  Figure  with theHsin-Yi Wen et al.  used a UHye Jin Kim et al.  Figure  used PVDJinze Li et al.  developeLin Zhao et al.  developeMuhammad Quisar Lokman et al.  investig2 on a planar optical waveguide to introduce humidity-dependent attenuation. A silicon wafer with a thermal oxide layer was used as the substrate and undercladding layer for the optical waveguide. Germanium and boron codoped silica layers were introduced into the substrate to form the core layer. The core layer was patterned using photolithography and etched using inductively coupled plasma (ICP) etching followed by spin coating of ZPU13 polymer to form the overcladding. The ZPU13 polymer coating was etched by using oxygen plasma down to the top surface of the waveguide core to enable evanescent wave interactions. The sensitivity is −2 dB/%RH between 56%RH and 90%RH, the response time is 2.5 s, and the dynamic range is 56%RH–90%RH. Pasquale Di Palma et al. [Nur Abdillah Siddiq et al.  exploitea et al.  exploredZhihai Liu et al.  Figure  investigCatherine Grogan et al.  conducteCheng Zhou et al.  reported2), molybdenum diselenide (MoSe2), and composition of graphene and graphene oxide (G/GO). The team analyzed the relative differentiation of attenuation as a function of RH. The conclusion was that G/GO was the most reliable coating among the three types. The tested dynamic range is 20%RH–90%RH. Husna Mardiyah Burhanuddin et al. [Erfan Owji et al.  chemicaln et al.  created Jia-Kai Wang et al.  exploredFor practical application, such as operation safety of transmission lines, Jie Zhang et al.  investigMao-qing Chen et al.  Figure  applied Sarah Kadhim Al-Hayali et al.  proposedSeyed Reza Hosseini Largani et al.  exploredXin Cheng et al.  Figure  employed2 was applied for humidity sensing. The sensing mechanism is evanescent wave attenuation. The response time is 25 s. The sensitivity is 5.35 µW/%RH between 15%RH and 50%RH and 1.94 µW/%RH between 50%RH and 95%RH. The dynamic range is 15%RH–95%RH. Yu Ying et al. [Xixi Huang et al.  depositeg et al.   and big data for smart cities of the near future.2-cladded optical fiber. The LOD is, on average, ~5%RH between 20%RH and 95%RH. The response time is 45 s. The sensing range depends on the number of sensing points. The underlying mechanics involve water absorption by the porous cladding, which scatters light and attenuates the output power. W. C. Michie et al. [K. Ogawa et al.  were amoe et al.  combinedA. Kharaz et al.  Figure  presenteA. Sascha Liehr et al.  were amoPeter J. Thomas et al.  also repGeorge Y. Chen et al.  Figure  created Humidity-induced strain measurement was investigated by Pavol Stajanca et al.  using poThere have been numerous functional materials applied to optical fibers as a coating to serve as a transducer to the target measurand, as shown in A large number of functional materials are composite and synthetic, which are either expensive or non-degradable. In addition, the production of sensitized composites is usually accompanied by by-products that cause environmental pollution . It is nThere are environments where water vapor is not the only component in addition to regular air, such as methane or carbon monoxide. To distinguish between a humid environment and one that is something else requires the functional material to be engineered in such a way that it only reacts to water vapor . Otherwise, false readings will render the humidity sensor useless. As for miniaturization, the reduction in the dimensions of sensors allows for the less-intrusive deployment or installation in space-limited areas. The challenge is to downscale components while maintaining precision and robustness. The ability to readily integrate with electronic systems enables multiplexing as well as the adoption of the IOT, which will play an increasingly bigger role in smart cities of the future. Seamless integration relies on the use of electronic components within a reasonable package size to perform the necessary conversions and amplifications to match the impedance and connector of the rest of the system.Cost reduction and lower maintenance add to the feasibility of employing such sensors and keeping them operational for long-term usage. One of the main limiters to the widespread use of specific sensors is the cost of upscaling and difficulty of maintenance. The hurdle to overcome includes mass production of the necessary components to lower the cost, as well as a simple design with long-lasting materials to minimize the need for regular maintenance. Protective membranes or components may be required to protect humidity sensors from dust and other forms of contamination, which will degrade the reliability of data over long.In terms of tradeoffs, thin functional coatings or thin optical fibers tend to offer a faster response at the cost of a lower sensitivity . Thick cThere are challenges associated with particular applications, ranging from respiratory monitoring to nuclear power plants. This section discusses the specific needs and difficulties to overcome for achieving a viable sensing solution.High levels of humidity can cause respiratory irritation , especiaConsidering the wearable nature of the application, the humidity sensor construction materials need to be able to cope with frequent or constant large strains and bending effects . FurtherSome clinical applications, such as laryngectomy, result in a bypass of the upper respiratory tract. As a result, the microclimate conditions of the nasal cavity and pharynx experience changes in the local temperature and RH . This caMildew is a critical problem in grain storage . If unchThe operational safety of transmission lines of power systems is subject to various environmental factors , includiNuclear power plants tend to employ condensate flow monitoring, sewage pool monitoring, and inspection of the main coolant inventory balance, allowing the total leakage to be measured quantitatively . HoweverThis review covered a wide range of humidity sensors reported in the literature to date. The motivation behind developing optical humidity sensors is clear, as humidity is an important parameter in a number of industries for quality control. The design choices and various challenges for different applications are also discussed. Fiber gratings, absorption loss, and micro-resonators lead the way in terms of design popularity. Some trends were observed between sensitivity, LOD, and response time, though not definitive due to the absence of a large set of reported parameters of interest. Some of the main difficulties in designing a practical humidity sensor for harsh environments include biocompatibility and contamination of the sensor head by the environment. The different functional materials used to sensitize the sensor heads are listed to offer an overview of the variety and to highlight the importance of material engineering in the field of sensors.From the trajectory of existing developments, future advances in humidity sensing are anticipated to strive toward higher specificity, better miniaturization, more compatible system/environment integration, lower costs, and lower maintenance. Better limit of detection is meaningless without mass demand for such accuracy, and thus existing specifications can meet the majority of requirements in this area. New materials, particularly 1D and 2D structures and nanoscale-precision engineering techniques, will drive the research and development of novel humidity sensors that can adapt to the demand of industries and also pave the way for new applications. Reliability and reproducibility are likely to be better with the steadily improving automated manufacturing tools elevated by Industry 4.0.


People with multiple sclerosis (MS) face challenges adhering to disease-modifying drug (DMD) treatment. Poor adherence to treatment reduces its clinical effectiveness which can adversely impact disease progression, MS-related hospitalisation, and mortality rates. Understanding the barriers to adherence is essential to addressing these issues in clinical practice and a consolidation of the literature had not yet been carried out. A systematic search was carried out using the electronic databases PsycINFO, and PubMed (Medline) using the search terms treatment compliance or treatment adherence and multiple sclerosis or MS. Studies included adults, with a diagnosis of relapsing–remitting MS (RRMS) (sample > 80% RRMS), taking a DMD. The studies used an adequate measurement of treatment adherence and analysed possible factors associated with adherence. A total of 349 studies were retrieved, of which 24 were considered eligible for inclusion. Overall adherence rates of the included studies ranged from 52 to 92.8%. Narrative synthesis revealed the most prevalent factors associated with adherence were age, gender, depression, cognition, treatment satisfaction, injection-site reactions, and injection anxiety. There was contradictory evidence for disability in association with treatment adherence. The findings should be used to inform the development of targeted patient support programs which improve treatment compliance. The review also highlights the opportunities for advancing research into treatment adherence in MS.The online version contains supplementary material available at 10.1007/s00415-021-10850-w. Adherence to long-term treatment can be challenging for those suffering from a chronic illness, such as multiple sclerosis. In a widely cited report, the World Health Organisation (WHO) stated that only 50% of patients adhere to treatment recommendations . It is tThere have been remarkable advancements in the last 20 years in developing MS drug treatments known as disease-modifying drugs (DMDs) which slow the progression of the disease and reduce the rate of relapse . CurrentMedication compliance or adherence is defined as “the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen” . This isAdherence to drug treatment in MS cannot be quantified using biological markers, therefore measuring adherence is often largely reliant on patients’ self-report . PatientAdherence to treatment in multiple sclerosis is crucial to optimising patient care and managing the long-term prognosis of people with MS. Developing a strong evidence base for the key factors associated with adherence will help inform the development of targeted interventions such as patient support programs which are focused on treatment compliance. The effectiveness of these interventions could be subsequently evaluated by measuring adherence rates and health-related outcomes specific to this population. The aim of the current review was to provide a synthesis of the factors associated with adherence to disease-modifying drugs in the treatment of multiple sclerosis.A comprehensive literature search was conducted according to the ‘PRISMA’  statement . StudiesThe studies included in existing systematic reviews related to drug adherence in multiple sclerosis were screened for eligibility for this review , 17. RefStudies were limited to those written in English and published in peer-reviewed journals. Studies were included if they assessed factor/s related to the adherence of disease-modifying drug treatments for multiple sclerosis and reported quantitative data. Studies were only included if participants had a confirmed diagnosis of relapse-remitting multiple sclerosis, or included a sub-group of whom > 80% had the relapse-remitting form, a criteria used in a recent review . StudiesOne reviewer (FW) extracted data from the studies directly into a table made specifically for the current review and this was examined and verified by a second reviewer (DL). Study characteristics which were extracted included: participant eligibility criteria, sample size and prescribed DMD, adherence measurement, adherence rate and the key findings. It was not possible to carry out a meta-analysis of the included studies due to methodological diversity, therefore a narrative synthesis of the key findings was conducted.The quality of each study and risk of bias was assessed using an adapted AXIS Critical Appraisal tool which included 12 items . For eacA total of 24 studies were included in the current review. Eight studies did not specify the participants’ MS subtype. These papers recorded the disease-modifying drugs that the participants were prescribed, which were only licensed for patients with relapsing–remitting MS . TherefoThe relevant data was extracted from the 24 included studies and can be found in the Supplementary Information, Table 1.n = 14). All included studies used the appropriate design for their research aims. No studies were excluded from the review following the quality assessment.Of the 24 studies, four adequately met all the 12 evaluated items and no studies were given a minus sign for more than three of the items . There were seven studies which recruited participants through an MS registry or health databases. One study also recruited participants through the US National MS Society and the media [The sample size of the studies varied from 53 to 17,599 participants and the majority of participants were recruited through out-patient clinics or neurology treatment centres . Of theMost of the included studies used questionnaires or scales to quantify potential predictors of adherence, alongside capturing participants’ sociodemographic information and the clinical characteristics of their MS. Several studies also gave participants surveys and provided qualitative comments or answered multiple-choice questions. This information was then used to carry out descriptive analysis of their perception of the contributing factors to non-adherence.The adherence rates of the studies range from 52 to 92.8%. The overall mean rates of adherence were pooled together based on the adherence measurement that was used by the study. It is important to note that the studies measured adherence across different time periods and used varying cut-offs. In addition, it was not possible to provide weighted means of adherence to the different disease-modifying drugs. Baseline adherence rates were used in the studies which had a longitudinal design. For the six studies which used pharmacy-based claims to measure adherence, either through the MPR or POC calculation, the mean rate of adherence was approximately 76.9%. The four studies which used an objective adherence measurement had a mean adherence rate of 80.55%. Finally, the mean rate of adherence of the self-reported studies was 74.0%.Several factors were significantly associated with adherence rates or were identified through descriptive analysis. The factors were systematically coded and used to generate descriptive themes.p = 0.0005). Lahdenperä et al. [p = 0.0112).All of the included studies analysed how sociodemographic characteristics related to adherence rates, and gender and age were the most consistently related. The review found four studies which showed that men had better treatment adherence than women and given that MS is more prevalent amongst females, this is of particular importance. Higuera et al.  used mulä et al.  also foup = 0.006) but older age was found to be a more consistent predictor of adherence. Thach et al. [p = 0.011). Zecca et al. [p = 0.008) and Higuera et al. [p < 0.01). Older age was also associated with adherence in Lahdenperä et al. [p < 0.0001). There is a lack of theoretical understanding in the literature about why age may predict adherence, particularly as confounding variables such as symptom stability and disability are often controlled for in studies.Six studies found older age to be positively associated with adherence, suggesting age is a strong predictor. Paolicelli et al.  reportedh et al.  found ada et al.  also foua et al. , using ta et al.  found thp < 0.05). Koskderelioglu et al. [p = 0.007). Consistent with this, Devonshire et al. [p = 0.02).Erbay et al.  found thu et al.  found the et al.  found thp < 0.001). Furthermore, adherent participants had also been taking their current disease-modifying drug for a shorter period of time (median = 30.0 months) than non-adherent participants . Similarly, McKay et al. [Devonshire et al.  found thy et al.  found thArroyo et al.  used a qp = 0.035). Erbay et al. [p = 0.0003) and Treadaway et al. [p < 0.001). Koltuniuk and Rosinczuk [p = 0.007 and p = 0.020, respectively). Similarly, the duration of these care activities were also positively associated with adherence (p < 0.05).In the de Seze et al.  study ady et al.  reportedy et al.  also fouosinczuk  used theosinczuk  examinedp < 0.0001). Paolicelli et a. [p = 0.015). In addition, Li et al. [p < 0.05). However, Zecca et al. [p = 0.008). Mckay et al. [Six studies assessed participants’ disability using the Expanded Disability Status Scale (EDSS) with mixed findings. Four studies found that higher disability was associated with non-adherence, however, two studies found that those with lower disability were more likely to be non-adherent. Koskderelioglu et al.  found thli et a.  demonstra et al.  found thy et al.  found a Psychological and behavioural factors.not important at all, 16.98% said it was a little important, 20.75% found it was moderately important and 18.86% found it was extremely important. In total, more than half the sample (56.59%) stated memory problems as important. Mckay et al. [A total of nine studies found that self-reported memory problems or forgetfulness were associated with poorer adherence or missing doses. Descriptive analysis carried out by Arroyo et al.  revealedy et al.  performey et al.  study.r = − 0.28, p < 0.05) and poorer delayed list recall . Between-group analyses of adherence revealed that poor adherers demonstrated poorer performance on a test of prospective memory compared to adequate adherers. Poor adherers also recalled fewer words after a delay (mean = 8.29 t(53) = 2.09, p < 0.05). Devonshire et al. [p < 0.0001). Inflammatory demyelination can result in cognitive deficit in up to 75% of people with MS and can be present in the very early stages of the condition [Two studies used quantitative scales to measure cognition; Bruce et al.  found the et al.  used theondition . Therefop < 0.001) and one objective measure (p = 0.001)). Worse scores for retrospective self-reported adherence were also associated with increased anxiety symptoms (p < 0.01). There were four studies which found that depression or depressive symptoms had an association with adherence rates. Koskderelioglu et al. [p = 0.006). The same scale was used by Treadaway et al. [p = 0.0009). Similarly, Higuera et al. [p < 0.0001). Neuropsychiatric comorbidities are prevalent amongst people with MS, a recent meta-analysis demonstrated consistent evidence for high prevalence rates of depression (31%) and anxiety (22%) in MS patients [A diagnosis of depression, symptoms of depression or at least one psychiatric disorder were associated with poorer adherence across five studies. Bruce et al.  found thu et al.  found thy et al. , who alsa et al.  also foua et al.  also foupatients .p < 0.0001), sentimental and sexual scales (p = 0.0068) and activities of daily living (p = 0.0021). Treadaway et al. [p < 0.0001), emotional well-being (p = 0.0012), social function (p = 0.0227), overall quality of life perception (p = 0.0001) and mental health composite scores (p < 0.0001). Similarly, Hao et al. [p = 0.05). In relation to psychological support, Siegel et al. [Devonshire et al.  analysedy et al.  also looo et al.  reportedl et al.  conductep = 0.008) and up to 14 times more likely to miss multiple doses (p = 0.008), than those who did not drink. Similarly, Mckay et al. [Tremlett et al.  found thy et al.  multivarn = 3) and injection-related reactions (n = 4) were commonly reported. Arroyo et al. [t(88) = 2.65, p < 0.01).Several studies captured medication-specific reasons for participant’s non-adherence to treatment, and injection anxiety . Studies did not provide separate analyses for different disease-modifying drugs prescribed, although 6 studies did adjust for the different frequencies of administration. It is possible that significant drivers of adherence within sub-groups have been masked by the grouped data.The study selection process highlighted the inconsistent operational definitions of adherence and persistence used in MS research. It is important for researchers to provide a clearer justification and understanding of these concepts and to use an adequate measure of adherence. The studies which adequately measured adherence which were included in the review have considerable methodological and clinical heterogeneity. The significant variability in adherence rates across studies may reflect this heterogeneity, therefore there is a need to develop a reliable, standardised measure of adherence. In the absence of this, studies should use more than one measure of adherence to increase ecological validity. In addition, the consistent use of the same outcome measures to quantify specific determining factors of adherence would improve the validity of findings. These methods of standardization would enable researchers to carry out a meta-analysis of the findings to draw more accurate and reliable conclusions. It would be useful to conduct longitudinal research across different time points to capture a better understanding of adherence across the course of the disease. Studies should also recruit participants who are prescribed second and third-line treatments so these can be separately systematically reviewed and then compared with first-line treatments. These findings would strengthen the evidence base for developing large-scale patient support programs and tailored interventions designed to improve compliance.Poor adherence to disease-modifying drug treatment in multiple sclerosis remains a challenge in clinical practice and has an adverse impact on prognosis. The current review has substantiated research into the factors associated with adherence, which includes gender, age, depression, cognition, treatment satisfaction and medication-specific issues. Priorities for future research include addressing the methodological and conceptual limitations of previous studies which will enable researchers to carry out meta-analyses. In an ageing population, the management of multiple sclerosis is likely to further contribute to a growing burden on healthcare services due to age-related comorbidities and further complications to disease management. Therefore, addressing issues related to adherence, and delivering interventions that improve compliance to treatment, is critical to minimising the personal and economic impact of the disease.Supplementary file1 (DOCX 28 kb)Below is the link to the electronic supplementary material.


Premna odorata’ by Abeer H. Elmaidomy et al., RSC Adv., 2020, 10, 10584–10598. DOI: 10.1039/D0RA01697GCorrection for ‘Triple-negative breast cancer suppressive activities, antioxidants and pharmacophore model of new acylated rhamnopyranoses from  The authors regret that the name of the author Asmaa I. Owis was incorrectly spelled as Asmsaa I. Owis in the original article. The correct author list is as displayed in this document.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.