A case study: The deployment of a novel in situ fluorimeter for monitoring biological contamination within the urban surface waters of Kolkata, India.

The quality and health of many of our vital freshwater systems are poor. To tackle this with ever increasing pressures from anthropogenic and climatic changes, we must improve water quality monitoring and devise and implement more appropriate water quality parameters. Recent research has highlighted the potential for Peak T fluorescence (tryptophan-like fluorescence, TLF) to monitor microbial activity in aquatic systems. The VLux TPro (Chelsea Technologies Ltd., UK), an in situ real-time fluorimeter, was deployed in different urban freshwater bodies within Kolkata (West Bengal, India) during March 2019. This study is the first to apply this technology in surface waters within a densely populated urban area. Spot-sampling was also undertaken at 13 sampling locations enabling physicochemical analysis, bacterial enumeration and determination of nutrient (nitrate and phosphate) concentrations. This case study has demonstrated the ability of an in situ fluorimeter, VLux TPro, to successfully identify both biological contamination events and potential elevated microbial activity, related to nutrient loading, in complex surface freshwaters, without the need for expensive and time-consuming laboratory analysis.

Understanding the Fertilizer Management Impacts on Water and Nitrogen Dynamics for a Corn Silage Tile-Drained System in Canada.

Effective management of dairy manure is important to minimize N losses from cropping systems, maximize profitability, and enhance environmental sustainability. The objectives of this study were (i) to calibrate and validate the DeNitrification-DeComposition (DNDC) model using measurements of silage corn ( L.) biomass, N uptake, soil temperature, tile drain flow, NO leaching, NO emissions, and soil mineral N in eastern Canada, and (ii) to investigate the long-term impacts of manure management under climate variability. The treatments investigated included a zero-fertilizer control, inorganic fertilizer, and dairy manure amendments (raw and digested). The DNDC model overall demonstrated statistically "good" performance when simulating silage corn yield and N uptake based on normalized RMSE (nRMSE) < 10%, index of agreement () > 0.9, and Nash-Sutcliffe efficiency (NSE) > 0.5. In addition, DNDC, with its inclusion of a tile drainage mechanism, demonstrated "good" predictions for cumulative drainage (nRMSE < 20%, > 0.8, and NSE > 0.5). The model did, however, underestimate daily drainage flux during spring thaw for both organic and inorganic amendments. This was attributed to an underestimation of soil temperature and soil water under frequent soil freezing and thawing during the 2013-2014 overwinter period. Long-term simulations under climate variability indicated that spring applied manure resulted in less NO leaching and NO emissions than fall application when manure rates were managed based on crop N requirements. Overall, this study helped highlight the challenges in discerning the short-term climate interactions on fertilizer-induced N losses compared with the long-term dynamics under climate variability.

The European Society of Paediatric Oncology Ependymoma-II program Core-Plus model: Development and initial implementation of a cognitive test protocol for an international brain tumour trial.

It is increasingly accepted that survival alone is an inadequate measure of the success of childhood brain tumour treatments. Consequently, there is growing emphasis on capturing quality of survival. Ependymomas are the third most frequently occurring brain tumours in childhood and present significant clinical challenges. European Society of Paediatric Oncology Ependymoma II is a comprehensive international program aiming to evaluate outcomes under different treatment regimens and improve diagnostic accuracy. Importantly, there has been agreement to lower the age at which children with posterior fossa ependymoma undergo focal irradiation from three years to either eighteen months or one year of age. Hitherto radiotherapy in Europe had been reserved for children over three years due to concerns over adverse cognitive outcomes following irradiation of the developing brain. There is therefore a duty of care to include longitudinal cognitive follow-up and this has been agreed as an essential trial outcome. Discussions between representatives of 18 participating European countries over 10 years have yielded European consensus for an internationally accepted test battery for follow-up of childhood ependymoma survivors. The 'Core-Plus' model incorporates a two-tier approach to assessment by specifying core tests to establish a minimum dataset where resources are limited, whilst maintaining scope for comprehensive assessment where feasible. The challenges leading to the development of the Core-Plus model are presented alongside learning from the initial stages of the trial. We propose that this model could provide a solution for future international trials addressing both childhood brain tumours and other conditions associated with cognitive morbidity.

The in situ bacterial production of fluorescent organic matter; an investigation at a species level.

Aquatic dissolved organic matter (DOM) plays an essential role in biogeochemical cycling and transport of organic matter throughout the hydrological continuum. To characterise microbially-derived organic matter (OM) from common environmental microorganisms (Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa), excitation-emission matrix (EEM) fluorescence spectroscopy was employed. This work shows that bacterial organisms can produce fluorescent organic matter (FOM) in situ and, furthermore, that the production of FOM differs at a bacterial species level. This production can be attributed to structural biological compounds, specific functional proteins (e.g. pyoverdine production by P. aeruginosa), and/or metabolic by-products. Bacterial growth curve data demonstrates that the production of FOM is fundamentally related to microbial metabolism. For example, the majority of Peak T fluorescence (> 75%) is shown to be intracellular in origin, as a result of the building of proteins for growth and metabolism. This underpins the use of Peak T as a measure of microbial activity, as opposed to bacterial enumeration as has been previously suggested. This study shows that different bacterial species produce a range of FOM that has historically been attributed to high molecular weight allochthonous material or the degradation of terrestrial FOM. We provide definitive evidence that, in fact, it can be produced by microbes within a model system (autochthonous), providing new insights into the possible origin of allochthonous and autochthonous organic material present in aquatic systems.

Assessing the antimicrobial potential of aerosolised electrochemically activated solutions (ECAS) for reducing the microbial bio-burden on fresh food produce held under cooled or cold storage conditions.

The main aim of this study was to assess the antimicrobial efficacy of electrochemically activated fog (ECAF) for reducing the microbial bio-burden on artificially inoculated fresh produce held under cooled (cucumber and vine tomatoes) or cold (rocket and broccoli) storage conditions. The ECAF treatment (1100 ± 5 mV ORP; 50 ± 5 mg L-1 free chlorine; 2.7 ± 0.1 pH) resulted in a significant log reduction in the potential pathogen E. coli recovered from rocket (2.644 Log10 CFU g-1), broccoli (4.204 Log10 CFU g-1), cucumber (3.951 Log10 CFU g-1) and tomatoes (2.535 Log10 CFU g-1) after 5 days. ECAF treatment also resulted in a significant log reduction in potential spoilage organisms, whereby a 3.533 Log10 CFU g-1, 2.174 Log10 CFU g-1 and 1.430 Log10 CFU g-1 reduction in presumptive Pseudomonads was observed for rocket, broccoli and cucumber respectively, and a 3.527 Log10 CFU g-1 reduction in presumptive Penicillium spp. was observed for tomatoes (after 5 days). No adverse visual effects on produce were recorded. The results of this study will inform industrial scale-up trials within commercial facilities (assessing shelf-life, microbial quality and organoleptic assessment) to assess the developed ECAF technology platform within a real food processing environment.

Environmental Electrokinetics for a sustainable subsurface.

Soil and groundwater are key components in the sustainable management of the subsurface environment. Source contamination is one of its main threats and is commonly addressed using established remediation techniques such as in-situ chemical oxidation (ISCO), in-situ chemical reduction (ISCR; most notably using zero-valent iron [ZVI]), enhanced in-situ bioremediation (EISB), phytoremediation, soil-washing, pump-and-treat, soil vapour extraction (SVE), thermal treatment, and excavation and disposal. Decades of field applications have shown that these techniques can successfully treat or control contaminants in higher permeability subsurface materials such as sands, but achieve only limited success at sites where low permeability soils, such as silts and clays, prevail. Electrokinetics (EK), a soil remediation technique mostly recognized in in-situ treatment of low permeability soils, has, for the last decade, been combined with more conventional techniques and can significantly enhance the performance of several of these remediation technologies, including ISCO, ISCR, EISB and phytoremediation. Herein, we discuss the use of emerging EK techniques in tandem with conventional remediation techniques, to achieve improved remediation performance. Furthermore, we highlight new EK applications that may come to play a role in the sustainable treatment of the contaminated subsurface.

In vitro discrimination of wound-associated bacteria by volatile compound profiling using selected ion flow tube-mass spectrometry.

AIMS: To determine if bacterial species responsible for clinically relevant wound infection produce specific volatile profiles that would allow their speciation. METHODS AND RESULTS: Selected ion flow tube-mass spectrometry (SIFT-MS) in full mass scan mode was used to analyse headspace gases produced by wound-associated bacteria grown in vitro, so as to enable identification of bacterial volatile product ion profiles in the resulting mass spectra. Applying multivariate statistical analysis (hierarchical clustering and principal component analysis) to the resultant mass spectra enabled clear speciation. Moreover, bacterial volatile product ions could be detected from artificially contaminated wound dressing material, although the pattern of product ions detected was influenced by culture conditions. CONCLUSIONS: Using selected product ions from the SIFT-MS mass spectra it is possible to discriminate wound-associated bacterial species grown under specific in vitro culture conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study have shown that wound-associated bacteria can be discriminated using volatile analysis in vitro and that bacterial volatiles can be detected from wound dressing material. This indicates that volatile analysis of wounds or dressing material to identify infecting microbes has potential and warrants further study.

Expression of eukaryotic-like protein in the microbiome of sponges.

Eukaryotic-like proteins (ELPs) are classes of proteins that are found in prokaryotes, but have a likely evolutionary origin in eukaryotes. ELPs have been postulated to mediate host-microbiome interactions. Recent work has discovered that prokaryotic symbionts of sponges contain abundant and diverse genes for ELPs, which could modulate interactions with their filter-feeding and phagocytic host. However, the extent to which these ELP genes are actually used and expressed by the symbionts is poorly understood. Here, we use metatranscriptomics to investigate ELP expression in the microbiomes of three different sponges (Cymbastella concentrica, Scopalina sp. and Tedania anhelens). We developed a workflow with optimized rRNA removal and in silico subtraction of host sequences to obtain a reliable symbiont metatranscriptome. This showed that between 1.3% and 2.3% of all symbiont transcripts contain genes for ELPs. Two classes of ELPs (cadherin and tetratricopeptide repeats) were abundantly expressed in the C. concentrica and Scopalina sp. microbiomes, while ankyrin repeat ELPs were predominant in the T. anhelens metatranscriptome. Comparison with transcripts that do not encode ELPs indicated a constitutive expression of ELPs across a range of bacterial and archaeal symbionts. Expressed ELPs also contained domains involved in protein secretion and/or were co-expressed with proteins involved in extracellular transport. This suggests these ELPs are likely exported, which could allow for direct interaction with the sponge. Our study shows that ELP genes in sponge symbionts represent actively expressed functions that could mediate molecular interaction between symbiosis partners.

Annually resolved North Atlantic marine climate over the last millennium.

Owing to the lack of absolutely dated oceanographic information before the modern instrumental period, there is currently significant debate as to the role played by North Atlantic Ocean dynamics in previous climate transitions (for example, Medieval Climate Anomaly-Little Ice Age, MCA-LIA). Here we present analyses of a millennial-length, annually resolved and absolutely dated marine δ18O archive. We interpret our record of oxygen isotope ratios from the shells of the long-lived marine bivalve Arctica islandica (δ18O-shell), from the North Icelandic shelf, in relation to seawater density variability and demonstrate that solar and volcanic forcing coupled with ocean circulation dynamics are key drivers of climate variability over the last millennium. During the pre-industrial period (AD 1000-1800) variability in the sub-polar North Atlantic leads changes in Northern Hemisphere surface air temperatures at multi-decadal timescales, indicating that North Atlantic Ocean dynamics played an active role in modulating the response of the atmosphere to solar and volcanic forcing.

'Lemonade Legs': Why do Some Patients Get Profound Hypomagnesaemia on Proton-Pump Inhibitors?

Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis.

Differential effect of race, education, gender, and language discrimination on glycemic control in adults with type 2 diabetes.

BACKGROUND: Discrimination has been linked to negative health outcomes, but little research has investigated different types of discrimination to determine if some have a greater impact on outcomes. We examined the differential effect of discrimination based on race, level of education, gender, and language on glycemic control in adults with type 2 diabetes. PATIENTS AND METHODS: Six hundred two patients with type 2 diabetes from two adult primary care clinics in the southeastern United States completed validated questionnaires. Questions included perceived discrimination because of race/ethnicity, level of education, sex/gender, or language. A multiple linear regression model assessed the differential effect of each type of perceived discrimination on glycemic control while adjusting for relevant covariates, including race, site, gender, marital status, duration of diabetes, number of years in school, number of hours worked per week, income, and health status. RESULTS: The mean age was 61.5 years, and the mean duration of diabetes was 12.3 years. Of the sample, 61.6% were men, and 64.9% were non-Hispanic black. In adjusted models, education discrimination remained significantly associated with glycemic control (ß=0.47; 95% confidence interval, 0.03, 0.92). Race, gender and language discrimination were not significantly associated with poor glycemic control in either unadjusted or adjusted analyses. CONCLUSIONS: Discrimination based on education was found to be significantly associated with poor glycemic control. The findings suggest that education discrimination may be an important social determinant to consider when providing care to patients with type 2 diabetes and should be assessed separate from other types of discrimination, such as that based on race.

Lumbosacral foraminal ratios and areas using MRI in medium-sized dogs.

OBJECTIVE: To examine conventional magnetic resonance imaging planes of the lumbosacral foramina to obtain objective measurements of foraminal size in medium-sized (20-28 kg) normal dogs. METHOD: Ten canine cadavers were evaluated using magnetic resonance imaging in neutral, flexed and extended position. Foraminal ratios, areas and lumbosacral angles were calculated and their relationship to body weight was evaluated. RESULTS: Foraminal ratios were found to be independent of body weight in medium sized dogs (p >0.42). Foraminal areas were dependent on body weight (p <0.05). Flexion and extension were shown to significantly change both the foraminal ratio and area. CLINICAL SIGNIFICANCE: Lumbosacral foraminal stenosis is common in working dogs. Foraminal ratios were evaluated in medium-sized dogs and were found to be independent of body weight, which may provide objective evaluation of surgical decompression techniques if calculated pre- and post-surgery. Foraminal areas were not independent of body weight.

Seasonal migration of Cnaphalocrocis medinalis (Lepidoptera: Crambidae) over the Bohai Sea in northern China.

The rice leaf roller, Cnaphalocrocis medinalis (Guenée), is a serious insect pest of rice with a strong migratory ability. Previous studies on the migration of C. medinalis were mostly carried out in tropical or subtropical regions, however, and what the pattern of seasonal movements this species exhibits in temperate regions (i.e. Northern China, where they cannot overwinter) remains unknown. Here we present data from an 11-year study of this species made by searchlight trapping on Beihuang Island (BH, 38°24'N; 120°55'E) in the centre of the Bohai Strait, which provides direct evidence that C. medinalis regularly migrates across this sea into northeastern agricultural region of China, and to take advantage of the abundant food resources there during the summer season. There was considerable seasonal variation in number of C. medinalis trapped on BH, and the migration period during 2003-2013 ranged from 72 to 122 days. Some females trapped in June and July showed a relatively higher proportion of mated and a degree of ovarian development suggesting that the migration of this species is not completely bound by the 'oogenesis-flight syndrome'. These findings revealed a new route for C. medinalis movements to and from Northeastern China, which will help us develop more effective management strategies against this pest.

How do client and therapists in online text therapy experience their exchanges and relationship?

The impact of online therapy text exchanges and the client-therapist alliance was compared to previously published means and standard deviations on face-to-face therapy using an aggregate benchmarking strategy. Further, the moderating effects of 4 participant factors found significant in the face-to-face therapy literature was investigated using mixed modeling analytic techniques. Thirty therapists and 30 clients visited an online site to report weekly to complete session impact and therapeutic alliance measures for a minimum of six weeks, which allowed for a naturalistic and nuanced examination of the process of online text psychotherapy. The impact of exchanges and client-therapist alliance in text therapy were similar to but in some respects more positive than previous evaluations of face-to-face therapy. A notable exception was substantially lower Arousal scores replicating the previously-observed online calming effect. The significance of participant factors previously found to influence impact and alliance in face-to-face therapy was not replicated except that therapists with the more symptomatic clients rated their text exchanges as less smooth and comfortable.

Bacterial chondronecrosis with osteomyelitis in broilers: influence of sires and straight-run versus sex-separate rearing.

Two experiments (E1, E2) were conducted to compare the influence of sires (sire A on dam C vs. sire B on dam C) and straight-run versus sex-separate rearing on the incidence of bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Fertile eggs from commercial breeder flocks were incubated and hatched at the University of Arkansas Poultry Research Hatchery. Male and female chicks were reared together (straight-run) or separately (sex-separate) in 3 × 3 m pens on litter or flat wire flooring with 65 (E1) or 60 (E2) birds per pen. Necropsies revealed lesions that are pathognomonic for BCO in ≥98% of the birds that became lame. The SigmaStat Z-test was used to compare cumulative BCO incidences through 8 wk of age. For birds reared on litter, the incidences of BCO were low regardless of cross or sex (range: 1.7 to 5.1%; P ≥ 0.6). Within a cross and sex, rearing the broilers straight-run versus sex-separate on wire flooring did not significantly affect the incidence of BCO. Significant incidences of BCO did not develop until after d 40. Males from the sire A cross developed a higher incidence of BCO than males from the sire B cross in E1 (27 vs. 17%, respectively; P = 0.009) but not in E2 (28.5 vs. 22.6%, respectively; P = 0.141). In both experiments, males from the sire A cross developed higher incidences of BCO than females from the sire B cross (27 vs. 11.9%, in E1; 28.5 vs. 14.8%, in E2). With the sexes pooled, broilers from the sire A cross consistently developed higher incidences of BCO than broilers from the sire B cross (21.4 vs. 14.9%, P = 0.005 in E1; 26.5 vs. 18.7%, P = 0.003 in E2). High susceptibilities to both femoral head (all femoral head necrosis = 66 to 85% incidences) and tibial head (all tibial head necrosis = 81 to 96% incidences) BCO lesions were demonstrated in lame birds from both sexes and crosses. This study supports a sire influence on the susceptibility of broilers to BCO. Sire lines can be chosen to reduce BCO susceptibility when broilers are grown beyond 6 wk of age.

Interannual Survival of Myotis lucifugus (Chiroptera: Vespertilionidae) near the Epicenter of White-Nose Syndrome.

Reduced populations of Myotis lucifugus (Little Brown Myotis) devastated by white-nose syndrome (WNS) persist in eastern North America. Between 2009 and 2013, we recaptured 113 marked individuals that survived between 1 and 6 winters in New England since the arrival of WNS. We also observed signs of reproductive success in 57 recaptured bats.

Is breastfeeding in infancy predictive of child mental well-being and protective against obesity at 9 years of age?

BACKGROUND: Preventing child mental health problems and child obesity have been recognized as public health priorities. The aim of the present study was to examine whether being breastfed (at all or exclusively) in infancy was a predictor of mental well-being and protective against risk of obesity at age 9. METHODS: Cross-sectional data from a large, nationally representative cohort study in the Republic of Ireland was used (n = 8357). Data on breastfeeding were retrospectively recalled. Child mental well-being was assessed using a parent-completed Strengths and Difficulties Questionnaire (SDQ). Child's height and weight were measured using scientifically calibrated instruments. RESULTS: Logistic regression analyses indicated that, after controlling for a wide range of potential confounding variables, being breastfed in infancy was associated with a 26% (P < 0.05) reduction in the risk of an abnormal SDQ score at 9 years. Being breastfed remained a significant predictor of child mental well-being when child obesity was controlled for, indicating that being breastfed, independent of child obesity, is a predictor of child mental well-being. The results of a second logistic regression indicated that, after controlling for a wide range of potential confounding variables, being breastfed for between 11 and 25 weeks was associated with a 36% (P < 0.05) reduction in the risk of obesity at 9 years, while being breastfed for 26 weeks or longer was associated with a 48% (P < 0.01) reduction in the risk of obesity at 9 years. CONCLUSIONS: Breastfeeding in infancy may protect against both poor mental well-being and obesity in childhood.

Susceptibility of 4 commercial broiler crosses to lameness attributable to bacterial chondronecrosis with osteomyelitis.

Growing broilers on wire flooring provides an excellent experimental model for exposing susceptibility to lameness attributable to bacterial chondronecrosis with osteomyelitis (BCO). Two independent experiments (E1, E2) were designed to compare the susceptibilities of broilers from 4 commercial crosses (W, X, Y, and Z). The standard crosses (W and Y) grow rapidly at an early age, whereas high-yield crosses (X and Z) initially tend to grow more slowly. Chicks were obtained from a commercial hatchery for E1, or were hatched at the University of Arkansas Poultry Research Hatchery for E2. Males and females were reared together (E1; n = 360/cross) or separately (E2; n = 390/cross) in 3 × 3 m pens on litter or wire flooring (wire). Necropsies revealed lesions that were pathognomonic for BCO in ≥94% of the birds that became lame. The SigmaStat Z-test was used to compare cumulative lameness incidences at 8 wk of age. For birds reared on litter, lameness incidences were low and did not differ between crosses or sexes (range: 2.2 to 4.6%; P ≥ 0.6). When males were reared on wire, their lameness incidences (by cross) were E1 = 52% for W(b); 42% for X(c); 69% for Y(a), and 44% for Z(bc); E2 = 31% for W(b); 19% for X(c); 49% for Y(a); and 25% for Z(bc). For females reared on wire, the lameness incidences were E1 = 40% for W(b), 30% for X(c), 49% for Y(a), and 28% for Z(c); E2 = 16% for W; 15% for X; 16% for Y; and 15% for Z (ns). Accordingly, the hierarchical ranking for BCO susceptibility by broiler cross was X ≤ Z ≤ W < Y for males in E1 and E2, for females in E1, and for males and females pooled in E1 and E2. Standard broiler crosses developed higher incidences of lameness than high-yield crosses, implicating an association between rapid early growth and susceptibility to BCO. Rearing the females separately on wire in E2 led to uniformly low incidences of BCO, regardless of cross. Stress-mediated immunosuppression contributes to the pathogenesis of BCO; perhaps female broilers experience less social or competitive stress when reared separately from their male hatch mates.

Pharmacokinetic-pharmacodynamic determinants of oseltamivir efficacy using data from phase 2 inoculation studies.

Given the limited understanding about pharmacokinetic-pharmacodynamic (PK-PD) determinants of oseltamivir efficacy, data from two phase 2 influenza virus inoculation studies were evaluated. Healthy volunteers in studies 1 and 2 were experimentally infected with influenza A/Texas (the concentration of neuraminidase inhibitor which reduced neuraminidase activity by 50% [IC(50)] = 0.18 nM) or B/Yamagata (IC(50) = 16.76 nM), respectively. In study 1, 80 subjects received 20, 100, or 200 mg of oral oseltamivir twice daily (BID), 200 mg oseltamivir once daily, or placebo for 5 days. In study 2, 60 subjects received 75 or 150 mg of oral oseltamivir BID or placebo for 5 days. Oseltamivir carboxylate (OC) (active metabolite) PK was evaluated using individual PK data and a population PK model to derive individual values for area under the concentration-time curve from 0 to 24 h (AUC(0-24)), minimum concentration of OC in plasma (C(min)), and maximum concentration of OC in plasma (C(max)). Exposure-response relationships were evaluated for continuous (area under composite symptom score curve [AUCSC], area under the viral titer curve, and peak viral titer) and time-to-event (alleviation of composite symptom scores and cessation of viral shedding) efficacy endpoints. Univariable analyses suggested the existence of intuitive and highly statistically significant relationships between OC AUC(0-24 )evaluated as a 3-group variable and AUCSC, time to alleviation of composite symptom scores, and time to cessation of viral shedding. The upper OC AUC(0-24) threshold (~14,000 ng · h/ml) was similar among these endpoints. Multivariable analyses failed to demonstrate the influence of study/strain on efficacy endpoints. These results provide the first demonstration of exposure-response relationships for efficacy for oseltamivir against influenza and suggest that OC exposures beyond those achieved with the approved oseltamivir dosing regimen will provide enhanced efficacy. The clinical applicability of these observations requires further investigation.