Pain and physical function belong to the core set of outcomes for

Pain and physical function belong to the core set of outcomes for phase III trials in osteoarthritis ( Bellamy 1997). Short-term (post-intervention) effects were analysed. Outcome measures were extracted by the principal author (MJJ). Two reviewers (MJJ and AFL) extracted information about the different intervention components. For each study and outcome measure, effect sizes were calculated using the difference in the mean change within the intervention and control group divided by the pooled baseline standard deviation. Positive values indicate that the intervention group improved on average more than the control group. Effect sizes of 0.2 to 0.5 can be interpreted as small,

trans-isomer in vitro 0.5 to 0.8 as moderate, and greater than 0.8 as large effects. To calculate the standard error of the effect size estimates, the pre-test post-test correlation must be known for the pain and function measurements within each study. Since this information was not available for any of the studies, we assumed a correlation of 0.6. All of the analyses were repeated using

an assumed correlation of 0.4 and 0.8, yielding essentially identical results. A meta-analysis was then conducted to obtain the average effect for the different intervention types and to compare these effects against each other. We anticipated MK0683 purchase that no trials might be found that directly compare any of the three interventions. Therefore we pre-planned a mixed-effects meta-regression model for this purpose, using restricted mafosfamide maximum likelihood estimation to estimate the amount of (residual) heterogeneity and using appropriate

dummy variables for the different intervention codes. To examine potential effect modification, we repeated this analysis including the type of control group (education/usual care/ultrasound vs none), study quality (EBRO score), treatment delivery mode (individual vs group), duration of treatment period (in weeks), treatment frequency per week, duration of treatment period × frequency, sex (% females), mean age of the sample, measurement instrument (WOMAC pain/function vs other) and type of weight bearing exercise used (non-weight bearing, weight bearing, or both) as covariates in the model. All analyses were carried out in R (version 2.10.1) using the ‘metafor’ package (Viechtbauer 2010). Of the 153 retrieved trials identified by the literature search, 21 were relevant. Twelve of these relevant studies were randomised controlled trials that met the inclusion and exclusion criteria. Figure 1 outlines the flow of studies through the review. Reasons for exclusion of the studies were: no non-exercise control group (Deyle et al 2005, Diracoglu et al 2005, McCarthy et al 2004, Veenhof et al 2006); no or only light strengthening exercises used in the intervention (Bautch et al 1997, Kovar et al 1992), and not possible to classify under one of the three codes.

Nunes et al Bobigny, France Cardiac sarcoidosis C  Chapelon-Abri

Nunes et al. Bobigny, France Cardiac sarcoidosis C. Chapelon-Abric, Paris, France Neurosarcoidosis: clinical manifestations, diagnosis and treatment K. Nozaki, Charleston, USA and M.A. Judson, Albany, USA Ocular sarcoidosis B. Bodaghi et al., Paris, France Skin manifestations

of sarcoidosis J. Mañá and J. Marcoval, Barcelona, Spain “
“L’approche quantitative de la vaccination. Une approche qualitative de la vaccination. “
“La méningite bactérienne est de diagnostic difficile et a une importante morbi-mortalité. Les délais de prise en charge ne sont pas toujours conformes aux recommandations. “
“Le ciment est l’agent le plus fréquemment incriminé dans les eczémas professionnels dans le secteur du bâtiment et des travaux publics (BTP). Il établit l’importance et le retentissement socio-économique des EPC dans le secteur du BTP. “
“Les lymphocytes

T coexprimant en Selleck PLX-4720 surface les molécules CD8+ et CD57+ représentent 1 à 15 % des lymphocytes totaux chez le sujet sain [1]. Leur nombre et leur proportion augmentent progressivement avec l’âge. Ces cellules peuvent prendre l’aspect cytologique de grands lymphocytes à grains (LGL) (figure 1A) ou celui de cellules hyperbasophiles d’un syndrome mononucléosique. Elles s’expandent au cours de maladies comme l’infection par le virus de l’immunodéficience humaine (VIH), certains déficits immunitaires acquis et accessoirement primitifs, certaines affections auto-immunes ou la réaction du greffon contre l’hôte. Elles peuvent alors devenir pathogènes en infiltrant les tissus ou en s’associant

à des cytopénies, en particulier des neutropénies. Selleckchem BMS354825 Les fonctions de ces lymphocytes ne sont que partiellement élucidées mais ils pourraient exercer principalement une action immunosuppressive. Ces expansion se distinguent des lymphoprolifération clonales à LGL (ou leucémies à LGL) qui représentent des maladies malignes [2], qui ne sont pas traitées ici. Dans toute situation où cette expansion also est importante ou inhabituelle, son interprétation doit inclure une analyse cytologique (et éventuellement cytogénétique) et une étude de la clonalité, ainsi qu’une analyse du contexte clinique (en cherchant en particulier un déficit immunitaire primitif ou acquis) afin de la distinguer d’une leucémie à LGL et d’orienter le diagnostic étiologique. Cet article a pour objectif de décrire les situations pathologiques au cours desquelles une expansion polyclonale de lymphocytes T CD8+/CD57+ peut être observée et de préciser les indications dans lesquelles la recherche d’une telle expansion peut avoir un intérêt diagnostique et/ou pronostique. CD57 (encore appelé HNK1, LEU-7 ou L2) est une glycoprotéine sulfatée de 110 kDa exprimée à la surface des cellules neurales des vertébrés, des lymphocytes T majoritairement CD8+ et des cellules NK [3], [4] and [5]. Plus rarement, elle est exprimée sur les lymphocytes T CD4+ et exceptionnellement, sur les lymphocytes T double-négatifs (CD4−/CD8−).

Consistent with these observations, humans with gonorrhea have el

Consistent with these observations, humans with gonorrhea have elevated serum IL-17 and IL-23 [38], and human monocyte-derived DCs secrete IL-23 and IL-10 upon stimulation with Gc in vitro [27] and [37]. Other mechanisms of immunosuppression include induction of apoptosis in antigen presenting cells (APC) through the NLRP3 inflammasome

pathway [33] and inhibition of DC-induced proliferation of T cells [32]. Gc Opa proteins that bind CEACAM1 3-MA datasheet were reported to down-regulate proliferation of activated CD4+ T cells and also B cells [39] and [40], although these findings have been questioned by others [41]. Gc also induces a polyconal IgM+ B cell response with poor specificity to the bacteria [42]. Mechanisms to evade specific antibodies include the expression of blocking antigens, production of IgA1 protease, molecular mimicry, retreat into epithelial cells, blebbing

of membranes to create a decoy, and changes in the antigenicity of surface molecules due to an extensive capacity for uptake and incorporation of DNA from other neisseriae, or in the case of Gc pili, recombination between the expressed pilin gene and silent loci. Phase variable expression of LOS biosynthesis genes and genes that encode surface molecules, buy PF-02341066 such as opa genes, also contributes to evasion of specific antibodies [43]. Progress on gonorrhea vaccines lags behind that of several other STIs for many reasons. First, repeat infections are common and correlates of protection

in humans have not been identified. Second, early vaccine efforts were frustrated by the highly antigenically variable surface of Gc and the lack of a small laboratory animal model for identifying protective responses and for systematic testing of antigens and immunization routes. Finally, there has been a lack of a concerted effort in this area. Only two antigens, killed whole cells and purified pilin, have been tested in clinical trials, which occurred however over 30 years ago and were unsuccessful [35]. These failures discouraged research, funding and commercial interest in gonorrhea vaccines. Advances in microbial pathogenesis, immunology, molecular epidemiology, combined with new infection models and the powerful new tools of genomics, proteomics and glycomics justify a renewed and intensified research focus on gonorrhea vaccine development. Knowledge of the specific immune mechanisms that protect against Gc infection is severely lacking. An estimated 20–35% of men become infected following a single exposure to an infected woman; the risk for women exposed to an infected man is estimated at 60–90% [44]. Comprehensive studies are needed to identify factors that might explain differential susceptibility to infection (Fig. 2). The lack of evidence that natural infection induces immunity to reinfection also seriously limits our ability to prospectively define the types of immune responses that an effective vaccine must induce.

The exclusion criteria were: Oswestry Disability Index score less

The exclusion criteria were: Oswestry Disability Index score less than 10, history of spinal surgery or fracture or diagnosis with an inflammatory disorder or fibromyalgia. Patients were also excluded if assessment suggested that they were experiencing lumbar radiculopathy (Wilk, 2004). All participants were given the same general advice, which was to continue using medication Dinaciclib cell line as prescribed

by their medical practitioner and to remain active (March et al 2004), but to avoid activities that aggravated their low back pain. All participants were instructed in a standardised exercise program and issued with a printed handout to reinforce the verbal instructions. The handout is available as an e-addendum (see Appendix 1). The exercise program consisted of three exercises that are commonly prescribed by physiotherapists for clients with low back pain: sidelying abdominal bracing (intended to activate deep abdominal stabilisers) (Richardson et al 1999), alternate knee-to-chest holds (Nicholas et al 2007), and side-to-side lumbar rotation (Olson 2007). Correct performance of side-lying abdominal Selleck VX-770 bracing was assessed

clinically by observing for a slight drawing-in of the lower abdominal wall below the umbilicus which is consistent with activation of the transversus abdominis muscle (Richardson et al 1999). Participants were asked to perform the exercises in a range that did not increase their pain, twice a day during the intervention period. The exercises were not progressed during the intervention period. Participants in the experimental group attended twice a week for two consecutive weeks and received Strain-Counterstrain treatment and review of the standardised exercises. Strain-Counterstrain treatment involved passive positioning of a participant, with varying degrees of spinal flexion/extension, lateral flexion and rotation, such that there was a two-thirds reduction in tenderness at a monitored digitally tender point (Jones et al 1995). This was determined by having participants rate their tenderness to palpation at digitally tender points on a numerical

pain scale where 10 represented initial tenderness science and 0 no tenderness. In addition to reported tenderness with intermittent probing, perceived tissue tension was used to guide the experimenter to the appropriate passive position (Jones et al 1995). The participant was passively maintained at this point by the experimenter for approximately 90 seconds, with intermittent probing at 30-sec intervals to ensure correct positioning, before being slowly and passively returned to a neutral position (Jones et al 1995, Kusunose and Wendorff, 1990, Kusunose, 1993). Treatment of a digitally tender point was considered successful if tenderness reduced by 70% or more (Kusunose, 1993, Kusunose and Wendorff, 1990).

, 2010) On the other hand, many studies suggest a neuroprotectiv

, 2010). On the other hand, many studies suggest a neuroprotective role for GM1 in several disease models (Krajnc et al., 1994, Lazzaro et al., 1994, Augustinsson et al., 1997, Svennerholm et al., 2002 and Sokolova et al., 2007). Several studies have addressed a pivotal role for GSK3β signaling pathway in neuronal death

and disease development observed in Alzheimer’s (Hooper et al., 2008, Hernández et al., 2009a and Hernández et al., 2009b). An amyloid induced activation (dephosphorylation) of GSK3β has been shown in some experimental models, and a correlation between its activity and the neurotoxicity triggered by this peptide. Koh et al. (2008) proposed the analysis of GSK3β phosphorylation as a biochemical parameter in the investigation of possible neuroprotective drugs. Organotypic hippocampal slice cultures are a considerable alternative to animal model experiments. GW-572016 in vivo Cultured slices maintain the cell architecture selleck products and interneuronal connections, allowing for a long in vitro survival period ( Stoppini et al., 1991 and Tavares et al., 2001). They have been used to

investigate molecular mechanisms involved in cytotoxicity, such as the ones that are determined by oxygen and glucose deprivation ( Valentim et al., 2003, Cimarosti et al., 2005, Zamin et al., 2006, Horn et al., 2005 and Horn et al., 2009) and Aβ toxicity ( Ito et al., 2003, Nassif et al., 2007 and Frozza et al., 2009). This methodology has also been used for DNA ligase neuroprotection

strategy evaluations ( Cimarosti et al., 2006, Simão et al., 2009, Bernardi et al., 2010 and Hoppe et al., 2010). The aim of this study was to examine the effect of Aβ treatment to organotypic hippocampal slice cultures on ganglioside expression, as well as the GM1 effect on Aβ-induced toxicity, as assessed by cellular death and GSK3β phosphorylation. Acrylamide, bisacrylamide, SDS and β-mercaptoethanol used in sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS–PAGE) were obtained from Sigma (St. Louis, MO, USA) as well as Aβ25–35, Aβ35–25, propidium iodide (PI), standard glycolipids and the ganglioside GM1 used in culture incubation. Polyclonal antibodies were purchased from Cell Signaling Technology (Beverly, MA, USA). Anti-rabbit IgG peroxidase-conjugated and reagents to detect chemiluminescence (ECL) were purchased from Amersham Pharmacia Biotech (Piscataway, NJ, USA). Millicell culture inserts (Millicell®-CM, 0.4 μm) were obtained from Millipore (Millipore®, Bedford, MA, USA), 6-well culture plates were from TPP (Tissue culture test plates TPP®, Switzerland). Culture medium, HBSS, fungizone and heat inactivated horse serum were obtained from GIBCO (Grand Island, NY, USA). Gentamicin was from Schering–Plough (Rio de Janeiro, Brazil). D-[1-C14] galactose (57 mCi/mmol) was obtained from Amersham Life Science (Buckinghamshire, UK). Silicagel high performance thin layer chromatography (HPTLC) plates were supplied by Merck (Darmstadt, Germany).

For example, of the 105 participants, only 27 (26%) had positive

For example, of the 105 participants, only 27 (26%) had positive provocative tests and arthroscopies for SL ligament injuries, 35 (33%) had positive provocative tests and arthroscopies for TFCC injuries, 17 (17%) had positive provocative tests and arthroscopies for lunate cartilage damage, 9 (9%) had positive provocative tests and arthroscopies for DRUJ injuries, 1 (1%) had positive provocative tests and arthroscopies for this website LT ligament injuries, and 2 (2%) had positive provocative tests and arthroscopies for arcuate injuries. Most tests appeared

to have little or no diagnostic value. Possible exceptions were positive findings from the SS test (+ve LR 2.88, 95% CI 1.68 to 4.92) and the MC test (+ve LR 2.67, 95% CI 0.83 to 8.60) and negative findings from the SS Navitoclax manufacturer test (–ve LR 0.28, CI 0.15 to 0.55) and the DRUJ test (–ve LR 0.3, CI 0.11 to 0.86), all of which were mildly useful. There were a number of incidental arthroscopic findings. Arthroscopic findings in addition to ligament injuries and lunate cartilage damage included synovitis (66, 63%), ganglions (17, 16%), and cartilage damage excluding the lunate (24, 23%). Table 2 cross-tabulates findings of MRI and arthroscopy. Positive MRI findings for SL ligament injuries (LR 4.17, 95% CI 1.54 to 11.30), TFCC injuries (LR 5.56, 95% CI 1.92 to 16.10), and lunate cartilage damage (LR 3.67, 95% CI

1.84 to 7.32) were of mild to moderate diagnostic usefulness. Negative MRI findings for SL ligament injuries (0.32, 95% CI 0.16 to 0.65), TFCC injuries (0.15, 95% CI 0.06 to 0.37), and lunate cartilage damage (0.33, 95% CI 0.14 to 0.78) were likewise of mild to moderate diagnostic

usefulness. The usefulness of both provocative tests and MRI for diagnosing no ligament injuries is summarised in Table 3 according to a recommended interpretation of positive and negative LRs (Portney and Watkins, 2009). The incremental diagnostic value of adding MRI to provocative tests was statistically significant for TFCC injuries and lunate cartilage damage, as shown in Table 4 (p < 0.001). An additional 13% of participants were correctly diagnosed as having or not having TFCC injuries with MRI over and above those correctly diagnosed with provocative tests alone. That is, for every eight scans there was one more correct diagnosis of the presence or absence of TFCC injury (ie, the NNS was eight). The NNS for lunate cartilage lesions was 13. MRI did not significantly improve diagnostic accuracy of any other ligament injury. MRI provided little incremental diagnostic accuracy because 72% to 95% of participants were diagnosed correctly by the provocative tests alone. This was partly because a large proportion of participants who went on to MRI did not have ligament injuries ( Table 2). Information about the accuracy of provocative tests for diagnosing wrist ligament injuries is important for clinicians.

The chloroform fraction of the extract at the dose of 200 mg/kg b

The chloroform fraction of the extract at the dose of 200 mg/kg body weight, like the standard anti-diarrhoeal agent (hyoscine butylbromide), caused a significant (p < 0.05) reduction in the intestinal fluid sodium ion concentration of rats in group 7 (209.00 ± 11.40) when compared to the value (227.00 ± 3.46) obtained for rats in the

castor oil-treated control group. As shown in Fig. 3, the methanol and the chloroform fractions of the extract Ribociclib ic50 at the tested doses (100 and 200 mg/kg body weight of each) significantly (p < 0.05) reduced the intestinal fluid potassium ion concentration of rats in groups 4, 5, 6 and 7 when compared to that of the rats in the castor oil-treated control group (group 2). The effects observed were dose-related with the intestinal fluid potassium ion concentration as 6.15 ± 1.75, 6.20 ± 1.70, 6.20 ± 1.23 and 5.65 ± 1.05 for rats in the 100 and 200 mg/kg body weight of the methanol fraction-treated groups (groups 4 and 5), 100 and 200 mg/kg body weight of the chloroform fraction-treated groups (groups 6 and 7) respectively when compared to the value (11.40 ± 2.98) obtained for rats in the castor oil-treated control group. The effects of the methanol and the chloroform fractions of the extract at the tested doses were comparable to that of the standard anti-diarrhoeal agent (hyoscine butylbromide) as shown in Fig. 3. The results of the qualitative and quantitative phytochemical analyses

of the chloroform and the methanol fractions of the chloroform–methanol extract of the leaves of P. americana showed, in both fractions of the extract, the presence and percentages of such bioactive constituents BGB324 solubility dmso as: alkaloids (2.67 ± 0.13% and 2.57 ± 0.06% in the chloroform and the methanol fractions respectively), flavonoids whatever (3.20 ± 0.17% and 2.95 ± 0.14% in the chloroform and the methanol fractions respectively), saponins (2.15 ± 0.08% and 2.23 ± 0.09% in the chloroform and the methanol fractions respectively), tannins

(2.48 ± 0.11% and 2.73 ± 0.13% in the chloroform and the methanol fractions respectively) and steroids (1.37 ± 0.04% and 1.10 ± 0.03% in the chloroform and the methanol fractions respectively). This indicates that the bioactive constituents present in the chloroform–methanol extract of the leaves of P. americana resided more in the chloroform fraction than in the methanol fraction. Reducing sugars, resins and acidic compounds were found to be absent in both fractions of the extract. The anti-diarrhoeal effect of both fractions of the extract shown in the present study could be, in part, due to the presence of tannins, alkaloids, saponins, flavonoids and steroids. In other words, it is possible that flavonoids and steroids, acting dually or in combination with other phytochemicals, produced the observed anti-diarrhoeal effect of both fractions of the chloroform–methanol extract of the leaves of P. americana.

Validity: Several publications have indicated that there are only

Validity: Several publications have indicated that there are only low correlations between walking distance and VO2max in children. The following Pearson’s correlations between 6MWT distance and VO2max are reported: juvenile idiopathic arthritis, r = 0.25; hemophilia, r = 0.31; spina bifida, r = 0.46; end-stage renal disease, r = –0.25. Recently it was reported that in children with pulmonary hypertension correlation between 6MWT distance

and VO2max was significant when the walk distance is lower than 300 m, and there was no association when the 6MWT distance was > 300 m ( Lammers et al 2011). Because of these low correlations, the 6MWT cannot be used as a replacement for a maximal exercise test ( Takken, 2010). C59 wnt order The 6MWT is an inexpensive instrument for measuring functional exercise capacity in paediatric populations. Care should be taken to ensure ON-01910 clinical trial appropriate execution of the test. Our experience from a recent unpublished survey among Dutch (paediatric) physiotherapists is there is a large variety in performance of the 6MWT among therapists, especially distance between turning points (variation 5–50 metres), lay-out of circuit (circle, squares, and even on treadmill), instructions for turning, as well as differences in encouragements. For optimal reliability

it is important that the test is performed in a standardised manner as recommended by the ATS (ATS, 2002). Furthermore, the various sets of reference values differ substantially. Therefore, it is advised to use the same those set of norm values all the time. “
“The International Standards for Classification of Spinal Cord Injury (ISCSCI) are widely used to classify the type and extent of a spinal cord injury (SCI) (American Spinal Injury Association 2003). The standards are based on comprehensive sensory and motor tests and are used to

derive right and left sensory and motor levels. Sensory and motor deficits can be summarised by tallying scores in different ways. For example, strength deficits in the upper limbs can be summarised by tallying the results of the upper limb motor tests (maximal score is 50). Importantly, the sensory and motor tests are also used to classify the type of spinal cord injury using the American Spinal Injury Association Impairment Scale (AIS). The important feature of the AIS is its definitions of complete and incomplete SCI. An SCI is only classified as incomplete if there is some sensory or motor function in the S4/5 segments, ie, if a person has anal sensation or the ability to voluntarily contract the anal sphincter. Validity and Reliability: The ISCSCI has good face validity because they were developed by expert and international consensus over a 20-year period. The Standards have two components: the physical examination and the classification.

Dilution corrected titres were reported for samples if results di

Dilution corrected titres were reported for samples if results did not fall within the quantifiable range of the standard curve. The assay has been adapted, standardized and validated at Department of Gastrointestinal Sciences, Christian Medical

College, Vellore. The lower limit cut off value for the assay is 7 units/mL. Stool specimens obtained 3, 5 and 7 days after each dose of BRV-TV vaccine/RotaTeq/Placebo were tested for rotavirus VP6 antigen using a commercial enzyme immunoassay kit (Premier Rota clone Qualitative EIA, Meridian Bioscience Inc., Cincinnati, USA). Each positive sample was also tested to determine the rotaviral Autophagy Compound Library order G and P types using reverse transcription PCR [22]. Healthy adult volunteers in Cohort 1 were kept under observation at the clinic for 30 min to

monitor for any immediate adverse events (Reactogenicity Events) after administration Pazopanib of the vaccine or placebo. Thereafter volunteers were given a thermometer and a Symptom Diary (SD) covering Days 0–10 for safety follow up. They were instructed to observe and record their axillary temperature twice daily as well as any Adverse Events (AEs) on the SD for 10 days after the dose of the BRV-TV vaccine/Placebo. Study volunteers were instructed to return to the clinic on Day 10 after administration of the BRV-TV vaccine/Placebo as an outpatient and whenever they had any symptoms. The diary card contained a list of solicited only events and blank spaces to capture any unsolicited events. All

healthy infants recruited in Cohort 2 were observed for 30 min post vaccination for immediate adverse events at the study site. Subsequently, the subject’s parents/guardians were given a thermometer, a Symptom Diary (SD) covering Days 0–6 and a second SD covering Days 7–27 for safety follow up following each of the three doses. They were instructed to observe and record their child’s axillary temperature twice daily as well as any AEs up to 7 days after each dose in the first SD, and from day 7 to day 27 in the second SD. Parents/guardians were instructed to bring the study infants to the study clinic on Day 7 and Day 28 after each administration of the BRV-TV vaccine/RotaTeq/Placebo as an outpatient and whenever any symptoms developed. The diary card contained list of solicited events and blank spaces to capture any unsolicited events. All the subjects in Cohort 2 were also evaluated for haematological and biochemical parameters before the first dose and 28 days after third dose of vaccine/placebo. An independent Data Safety Monitoring Board (DSMB) oversaw the trial and had access to all the safety information subsequent to each dose and the study randomization codes. The DSMB was empowered to recommend the stopping of the trial in the event of any safety concerns with the BRV-TV vaccine/RotaTeq/Placebo.

These differences indicate that the remaining severity classifica

These differences indicate that the remaining severity classification discrepancies between the VSS and the CSS may be due, not only to the severity threshold chosen, but also to the differences in individual item scoring. In order to obtain equivalent severity cutoffs between the two scoring systems, item cutoffs should be reconsidered. While FG-4592 solubility dmso better consistency between severity score cutoffs could be achieved, due to the differences in items included in each scoring system and because the

CSS is affected more by missing a symptom than the VSS (i.e. CSS does not provide a point score for the number of diarrhea episodes until two episodes have occurred and for the duration of vomiting until 2 days of vomiting have passed), it is unlikely that

the severity scores would ever identify the exact same proportions of Proteases inhibitor severe disease in any population. Weaknesses of this post-hoc analysis included that the trials were designed to capture moderate to severe cases and, as explained in the main efficacy manuscript for Africa [8], despite common case capture methods, success in capturing cases differed between sites and regions. The challenges in capturing and scoring cases for the Mali site are described in this supplement [28]. Despite this, scoring distributions for the VSS and the CSS appeared normal in each region. Additionally, diary cards were not used to collect symptoms at home in these trials and, depending on healthcare seeking behaviors, the average time from symptom onset to clinic assessment varied by participant and site, thus leaving

some sites more dependent on parental recall than others and allowing episode severity to develop further before seeking treatment at a healthcare facility. Larger discrepancies were identified between the two scoring systems in Asia as compared to Africa; the scoring systems, originally developed for use in middle- to high-income countries, did not perform similarly others across low-income regions. For the CSS, this may be due to differences between regions in interpretation and understanding of subjective items, like behavior and temperature duration. For the VSS, this may be due to differences in rehydration and hospitalization patterns between regions. It was also observed that, based on the number of participants enrolled at each site, some sites captured an increased number of cases as compared to other sites which may have been due to differences in medical facility utilization by site, indicating a challenge of running any multi-center trial and trying to ensure that case capture methods are identical, regardless of cultural differences in health care seeking behaviors.