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Abstract Soil sampling for environmental DNA in remote and semi-remote locations is often limited due to logistical constraints surrounding sample preservation, including no or limited access to a freezer. Freezing at − 20 °C is a common DNA preservation strategy, however, other methods such as desiccation, ethanol or commercial preservatives are available as potential alternative DNA preservation methods for room temperature storage. In this study, we assessed five preservation methods (CD1 solution, 95% Ethanol, Dry & Dry silica gel packs, RNAlater, LifeGuard) along with freezing at − 20 °C, against immediate extraction on organic and mineral soils for up to three weeks of preservation. We assessed direct effects on DNA concentration and quality, and used DNA metabarcoding to assess effects on bacterial and fungal communities. Drying with Dry & Dry led to no significant differences from immediate extraction. RNAlater led to lower DNA concentrations, but effects on community structures were comparable to freezing. CD1, LifeGuard and Ethanol either caused immediate significant shifts in community structure, degradation of DNA quality or changes in diversity metrics. Overall, our study supports the use of drying with silica gel packs as a cost-effective, and easily applied method for the short-term storage at room temperature for DNA-based microbial community analyses.

Abstract MIS-C is a systemic inflammation disorder with poorly characterised immunopathological mechanisms. We compared changes in the systemic immune response in children with MIS-C (n = 12, 5–13 years) to healthy controls (n = 14, 5–15 years). Analysis was done in whole blood treated with LPS. Expression of CD11b and Toll-like receptor-4 (TLR4) in neutrophils and monocytes were analysed by flow cytometry. Serum cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-Ira, TNF-α, TNF-β, IFN-Υ, VEGF, EPO and GM-CSF) and mRNA levels of inflammasome molecules (NLRP3, ASC and IL-1β) were evaluated. Subpopulations of lymphocytes (CD3+, CD19+, CD56+, CD4+, CD8+, TCR Vδ1+, TCR Vδ2+) were assessed at basal levels. Absolute counts of neutrophils and NLR were high in children with MIS-C while absolute counts of lymphocytes were low. Children with MIS-C had increased levels of IL-6, IL-10, TNF-β and VEGF serum cytokines at the basal level, and significantly increased TNF-β post-LPS, compared to controls. IL-1RA and EPO decreased at baseline and post-LPS in MIS-C patients compared to controls. The percentage of CD3+ cells, NK cells and Vδ1 was lower while B cells were higher in children with MIS-C than in controls. Dysregulated immune response in children with MIS-C was evident and may be amenable to immunomodulation.

Abstract In recent ages, green nanotechnology has gained attraction in the synthesis of metallic nanoparticles due to their cost-effectiveness, simple preparation steps, and environmentally-friendly. In the present study, copper oxide nanoparticles (CuO NPs) were prepared using Parthenium hysterophorus whole plant aqueous extract as a reducing, stabilizing, and capping agent. The CuO NPs were characterized via UV–Vis Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), powder X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Dynamic Light Scattering (DLS). The UV–Vis spectra of CuO NPs showed a surface plasmonic resonance band to occur at 340 nm. FTIR analysis revealed the presence of secondary metabolites on the surface of CuO NPs, with a characteristic Cu–O stretching band being identified at 522 cm−1. Scanning electron micrographs and transmission electron micrographs showed that CuO NPs were nearly spherical, with an average particle of 59.99 nm obtained from the SEM micrograph. The monoclinic crystalline structure of CuO NPs was confirmed using XRD, and crystallite size calculated using the Scherrer-Debye equation was found to be 31.58 nm. DLS showed the presence of nanoparticle agglomeration, which revealed uniformity of the CuO NPs. Furthermore, the degradation ability of biosynthesized nanoparticles was investigated against rifampicin antibiotic. The results showed that the optimum degradation efficiency of rifampicin at 98.43% was obtained at 65℃ temperature, 50 mg dosage of CuO NPs, 10 mg/L concentration of rifampicin solution, and rifampicin solution at pH 2 in 8 min. From this study, it can be concluded that CuO NPs synthesized from Parthenium hysterophorus aqueous extract are promising in the remediation of environmental pollution from antibiotics. In this light, the study reports that Parthenium hysterophorus-mediated green synthesis of CuO NPs can effectively address environmental pollution in cost-effective, eco-friendly, and sustainable ways.

Abstract Recent findings of microplastics in marine food such as fish, crabs and shrimps necessitate the need to develop biodegradable packaging materials. This study reports on the development of a biodegradable packing material from cellulose nanofibril-polyvinyl alcohol nanocomposite embedded with silver nanoparticles. Microcrystalline cellulose was isolated from sugarcane bagasse via the kraft process followed by conversion of cellulose I to cellulose II using NaOH/urea/water solution. The nanofibrils were then isolated using (2,2,6,6-Tetramethylpiperidin-1-yl) oxyl (TEMPO) and used as a reinforcing element in polyvinyl alcohol composite prepared through solvent casting. The tensile strength, water solubility, optical properties, water vapor permeability and wettability of the prepared films were then evaluated. The antimicrobial potency of the films was evaluated using the disc diffusion antimicrobial assay against selected microorganisms.

BackgroundMaternal near-miss refers to women who survive death from life-threatening obstetric complications and has various social, financial, physical, and psychological impacts on families.ObjectiveTo explore male partners' perceptions of maternal near-miss experienced by their female partners and the associated psychosocial impacts on their families in Rwanda.MethodsThis was a qualitative study involving 27 semi-structured in-depth interviews with male partners whose spouses experienced a maternal near-miss event. Data were analyzed using a thematic coding to generate themes from participants' responses.ResultsSix key themes that emerged were: male partner's support during wife's pregnancy and during maternal near-miss hospitalization, getting the initial information about the spouse's near-miss event, psychosocial impacts of spouse's near-miss, socio-economic impact of spouse's near-miss, post- maternal near-miss family dynamics, and perceived strategies to minimize the impacts of near-miss. Male partners reported emotional, social, and economic impacts as a result of their traumatic experiences.ConclusionsThe impact of maternal near-miss among families in Rwanda remains an area that needs healthcare attention. The residual emotional, financial, and social consequences not only affect females, but also their male partners and their relatives. Male partners should be involved and be well-informed about their partners' conditions and the expected long-term effects of near-miss. Also, medical and psychological follow-up for both spouses is necessary for the enhancement of the health and well-being of affected households.

The objective of this study was to develop a serum biochemical marker of the degradation of type III and IV collagens, as an index of synovium turnover, and evaluate its performance in patients with rheumatoid arthritis (RA). An enzyme-linked immunosorbent assay for serum synovial collagen fragments (Col3-4) was developed using an antibody recognizing a specific sequence from human type III collagen, which shares 70% homology with type IV collagen. Immunohistochemistry was performed to localize Col3-4 and the matrix metalloprotease MMP-9 which is upregulated in RA synovial fibroblasts in the synovial tissue from a RA patient. Serum Col3-4 was measured in patients with RA (n = 66, 73% women, mean age 62 years, median disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) 2.6) and in sex and age matched healthy controls (n = 70, 76% women, mean age 59 years). Col3-4 immunoassay demonstrated adequate analytical performances and recognized a circulating neoepitope resulting from the cleavage of type III and IV collagens. In RA synovium tissue, Col3-4 fragments were localized in the lining layer where destructive fibroblasts are present and around blood vessels rich in type IV collagen. MMP-9 colocalized with Col3-4 staining and efficiently released Col3-4 fragments from type III and type IV collagen digestion. Serum Col3-4 was markedly increased in patients with RA (+240% vs controls, p < 0.0001) and correlated with DAS28-ESR (r = 0.53, p < 0.0001). Patients with RA and active disease (DAS28-ESR > 3.2, n = 20) had 896% (p < 0.0001) higher levels than subjects with low activity (n = 46). Serum Col3-4 is a specific and sensitive biochemical marker reflecting MMP- mediated type III and IV collagen degradation from synovial tissue. Serum Col3-4 levels are markedly increased in patients with RA, particularly in those with active disease, suggesting that it may be useful for the clinical investigation of RA.

BackgroundThe introduction of robot-assisted surgery is costly and requires whole system transformation, which makes the assessment of benefits (or drawbacks) complex. To date, there has been little agreement on which outcomes should be used in this regard. The aim of the RoboCOS study was to develop a core outcome set for the evaluation of robot-assisted surgery that would account for its impact on the whole system.MethodsIdentification of a long-list of potentially relevant outcomes through systematic review of trials and health technology assessments; interviews with individuals from a range of stakeholder groups (surgeons, service managers, policy makers and evaluators) and a focus group with patients and public; prioritisation of outcomes via a 2-round online international Delphi survey; consensus meeting.Results721 outcomes were extracted from the systematic reviews, interviews and focus group which were conceptualised into 83 different outcome domains across four distinct levels (patient, surgeon, organisation and population) for inclusion in the international Delphi prioritisation survey (128 completed both rounds). The consensus meeting led to the agreement of a 10-item core outcome set including outcomes at: patient level (treatment effectiveness; overall quality of life; disease-specific quality of life; complications (including mortality); surgeon level (precision/accuracy; visualisation); organisation (equipment failure; standardisation of operative quality; cost-effectiveness); and population (equity of access).ConclusionThe RoboCOS core outcome set, which includes the outcomes of importance to all stakeholders, is recommended for use in all future evaluations of robot-assisted surgery to ensure relevant and comparable reporting of outcomes.

The objective of this study was to develop a serum biochemical marker of the degradation of type III and IV collagens, as an index of synovium turnover, and evaluate its performance in patients with rheumatoid arthritis (RA). An enzyme-linked immunosorbent assay for serum synovial collagen fragments (Col3-4) was developed using an antibody recognizing a specific sequence from human type III collagen, which shares 70% homology with type IV collagen. Immunohistochemistry was performed to localize Col3-4 and the matrix metalloprotease MMP-9 which is upregulated in RA synovial fibroblasts in the synovial tissue from a RA patient. Serum Col3-4 was measured in patients with RA (n = 66, 73% women, mean age 62 years, median disease activity score 28 with erythrocyte sedimentation rate (DAS28-ESR) 2.6) and in sex and age matched healthy controls (n = 70, 76% women, mean age 59 years). Col3-4 immunoassay demonstrated adequate analytical performances and recognized a circulating neoepitope resulting from the cleavage of type III and IV collagens. In RA synovium tissue, Col3-4 fragments were localized in the lining layer where destructive fibroblasts are present and around blood vessels rich in type IV collagen. MMP-9 colocalized with Col3-4 staining and efficiently released Col3-4 fragments from type III and type IV collagen digestion. Serum Col3-4 was markedly increased in patients with RA (+240% vs controls, p < 0.0001) and correlated with DAS28-ESR (r = 0.53, p < 0.0001). Patients with RA and active disease (DAS28-ESR > 3.2, n = 20) had 896% (p < 0.0001) higher levels than subjects with low activity (n = 46). Serum Col3-4 is a specific and sensitive biochemical marker reflecting MMP- mediated type III and IV collagen degradation from synovial tissue. Serum Col3-4 levels are markedly increased in patients with RA, particularly in those with active disease, suggesting that it may be useful for the clinical investigation of RA.

Background The introduction of robot-assisted surgery is costly and requires whole system transformation, which makes the assessment of benefits (or drawbacks) complex. To date, there has been little agreement on which outcomes should be used in this regard. The aim of the RoboCOS study was to develop a core outcome set for the evaluation of robot-assisted surgery that would account for its impact on the whole system. Methods Identification of a long-list of potentially relevant outcomes through systematic review of trials and health technology assessments; interviews with individuals from a range of stakeholder groups (surgeons, service managers, policy makers and evaluators) and a focus group with patients and public; prioritisation of outcomes via a 2-round online international Delphi survey; consensus meeting. Results 721 outcomes were extracted from the systematic reviews, interviews and focus group which were conceptualised into 83 different outcome domains across four distinct levels (patient, surgeon, organisation and population) for inclusion in the international Delphi prioritisation survey (128 completed both rounds). The consensus meeting led to the agreement of a 10-item core outcome set including outcomes at: patient level (treatment effectiveness; overall quality of life; disease-specific quality of life; complications (including mortality); surgeon level (precision/accuracy; visualisation); organisation (equipment failure; standardisation of operative quality; cost-effectiveness); and population (equity of access). Conclusion The RoboCOS core outcome set, which includes the outcomes of importance to all stakeholders, is recommended for use in all future evaluations of robot-assisted surgery to ensure relevant and comparable reporting of outcomes.

BackgroundOften considered an "invisible disability", hearing loss is one of the most prevalent chronic diseases and the third leading cause for years lived with disability worldwide. Hearing loss has substantial impacts on communication, psychological wellbeing, social connectedness, cognition, quality of life, and economic independence. The Hearing impairment in Adults: a Longitudinal Outcomes Study (HALOS) aims to evaluate the: (1) impacts of hearing devices (hearing aids and/or cochlear implants), (2) differences in timing of these interventions and in long-term outcomes between hearing aid and cochlear implant users, and (3) cost-effectiveness of early intervention for adult-onset hearing loss among hearing device users.Materials and methodsHALOS is a mixed-methods study collecting cross-sectional and longitudinal data on health and social outcomes from 908 hearing aid and/or cochlear implant users aged ≥40 years, recruited from hearing service providers across Australia. The quantitative component will involve an online survey at baseline (time of recruitment), 24-months, and 48-months and will collect audiological, health, psychosocial, functional and employment outcomes using validated instruments. The qualitative component will be conducted in a subset of participants at baseline and involve semi-structured interviews to understand the patient journey and perspectives on the Australian hearing service model.EthicsThis study has been approved by the Macquarie University Human Research Ethics Committee (ID: 11262) and Southern Adelaide Local Health Network (ID: LNR/22/SAC/88). Dissemination of results: Study findings will be disseminated to participants via a one-page summary, and to the public through publications in peer-reviewed journals and presentations at conferences.Trial registrationAustralia New Zealand Clinical Trial Registry (ANZCTR) registration number: ACTRN12622000752763.

Abstract Determining the mechanisms driving range-wide reductions in Atlantic salmon marine survival is hindered by an insufficient understanding of their oceanic ecology and distribution. We attached 204 pop-up satellite archival tags to post-spawned salmon when they migrated to the ocean from seven European areas and maiden North American salmon captured at sea at West Greenland. Individuals migrated further north and east than previously reported and displayed increased diving activity near oceanographic fronts, emphasizing the importance of these regions as feeding areas. The oceanic distribution differed among individuals and populations, but overlapped more between geographically proximate than distant populations. Dissimilarities in distribution likely contribute to variation in growth and survival within and among populations due to spatio-temporal differences in environmental conditions. Climate-induced changes in oceanographic conditions will alter the location of frontal areas and may have stock-specific effects on Atlantic salmon population dynamics, likely having the largest impacts on southern populations.

IntroductionThe COVID-19 pandemic has impacted population health around the globe, directly and indirectly. The objective of this study was to document changes in HIV care associated with the COVID-19 pandemic at selected clinics in Central Africa, along with clinic-level strategies for minimizing disruptions in HIV care and treatment for people with HIV (PWH).MethodsA 51-item questionnaire on COVID-19 pandemic-associated changes in HIV service delivery was completed by clinicians involved in HIV care at 21 clinics in five countries participating in Central Africa International epidemiology Databases to Evaluate AIDS (CA-IeDEA). The survey was completed at two timepoints: June-July 2020 and October 2020 to February 2021. Descriptive statistics were used to characterize changes in HIV care and related services.ResultsWhile 81% of sites reported at least one negative consequence of COVID-19 for clinic operations during the first survey, none reported suspending antiretroviral therapy (ART) initiation services for new patients, and 24% reported adopting telemedicine. In the follow-up survey, fewer sites (48%) reported at least one disruption to clinic operations, and more sites reported mitigation strategies, including expanding rapid ART initiation services and providing extra supplies of ART medications to reduce visit frequency. In the follow-up survey, more sites, especially in Rwanda, reported stockouts of commodities, including HIV and viral load testing and HIV pre-exposure prophylaxis. More than one-fifth of sites reported stockouts of second- or third-line ART at each survey timepoint.ConclusionsWhile the initial wave of the COVID-19 pandemic resulted in concerning disruptions to HIV service delivery at CA-IeDEA sites, most of these disruptions attenuated over time, and many sites introduced measures to help PWH avoid frequent visits to the clinic for care and medications. The impact of HIV commodity stockouts and clinic mitigation strategies on treatment outcomes needs to be assessed.

Introduction The COVID-19 pandemic has impacted population health around the globe, directly and indirectly. The objective of this study was to document changes in HIV care associated with the COVID-19 pandemic at selected clinics in Central Africa, along with clinic-level strategies for minimizing disruptions in HIV care and treatment for people with HIV (PWH). Methods A 51-item questionnaire on COVID-19 pandemic-associated changes in HIV service delivery was completed by clinicians involved in HIV care at 21 clinics in five countries participating in Central Africa International epidemiology Databases to Evaluate AIDS (CA-IeDEA). The survey was completed at two timepoints: June-July 2020 and October 2020 to February 2021. Descriptive statistics were used to characterize changes in HIV care and related services. Results While 81% of sites reported at least one negative consequence of COVID-19 for clinic operations during the first survey, none reported suspending antiretroviral therapy (ART) initiation services for new patients, and 24% reported adopting telemedicine. In the follow-up survey, fewer sites (48%) reported at least one disruption to clinic operations, and more sites reported mitigation strategies, including expanding rapid ART initiation services and providing extra supplies of ART medications to reduce visit frequency. In the follow-up survey, more sites, especially in Rwanda, reported stockouts of commodities, including HIV and viral load testing and HIV pre-exposure prophylaxis. More than one-fifth of sites reported stockouts of second- or third-line ART at each survey timepoint. Conclusions While the initial wave of the COVID-19 pandemic resulted in concerning disruptions to HIV service delivery at CA-IeDEA sites, most of these disruptions attenuated over time, and many sites introduced measures to help PWH avoid frequent visits to the clinic for care and medications. The impact of HIV commodity stockouts and clinic mitigation strategies on treatment outcomes needs to be assessed.

Abstract Predation and mortality are often difficult to estimate in the ocean, which hampers the management and conservation of marine fishes. We used data from pop-up satellite archival tags to investigate the ocean predation and mortality of adult Atlantic salmon (Salmo salar) released from 12 rivers flowing into the North Atlantic Ocean. Data from 156 tagged fish revealed 22 definite predation events (14%) and 38 undetermined mortalities (24%). Endothermic fish were the most common predators (n = 13), with most of these predation events occurring in the Gulf of St. Lawrence and from the Bay of Biscay to the Irish Shelf. Predation by marine mammals, most likely large deep-diving toothed whales (n = 5), and large ectothermic fish (n = 4) were less frequent. Both the estimated predation rates (ZP) and total mortality rates (ZM) where higher for Atlantic salmon from Canada, Ireland, and Spain (ZP = 0.60–1.32 y−1, ZM = 1.73–3.08 y−1) than from Denmark and Norway (ZP = 0–0.13 y−1, ZM = 0.19–1.03 y−1). This geographical variation in ocean mortality correlates with ongoing population declines, which are more profound for southern populations, indicating that low ocean survival of adults may act as an additional stressor to already vulnerable populations.

Objectives We evaluated whether implementation of lockdown orders in South Africa affected ambulatory clinic visitation in rural Kwa-Zulu Natal (KZN).Design Observational cohortSetting Data were analysed from 11 primary healthcare clinics in northern KZN.Participants A total of 46 523 individuals made 89 476 clinic visits during the observation period.Exposure of interest We conducted an interrupted time series analysis to estimate changes in clinic visitation with a focus on transitions from the prelockdown to the level 5, 4 and 3 lockdown periods.Outcome measures Daily clinic visitation at ambulatory clinics. In stratified analyses, we assessed visitation for the following subcategories: child health, perinatal care and family planning, HIV services, non-communicable diseases and by age and sex strata.Results We found no change in total clinic visits/clinic/day at the time of implementation of the level 5 lockdown (change from 90.3 to 84.6 mean visits/clinic/day, 95% CI −16.5 to 3.1), or at the transitions to less stringent level 4 and 3 lockdown levels. We did detect a >50% reduction in child healthcare visits at the start of the level 5 lockdown from 11.9 to 4.7 visits/day (−7.1 visits/clinic/day, 95% CI −8.9 to 5.3), both for children aged

INTRODUCTION: Several studies have shown that older people have a higher risk of exposure to viral hepatitis B and C than younger people. This study aimed to determine the seroprevalence of hepatitis B and C and their associated factors in people aged 45+ years old in Burera, a rural district of Rwanda. METHODS: a cross sectional study was conducted from July to December 2017 during a mass campaign of hepatitis B (HBV) and hepatitis C (HCV) screening and vaccination of eligible populations against HBV in Burera District. Blood samples were collected and hepatitis B surface antigen (HBsAg) and an antibody against hepatitis C (Anti-HCV) were detected using an Enzyme-Linked Immuno-Sorbent Assay (ELISA). The associated factors were identified using a structured questionnaire and the data was analyzed using SPSS software. RESULTS: of the 374 people included in this study, 53.2% were females. The median age was 56 years old with an interquartile range (IQR) of 50 - 63 years old. The prevalence of HBV and HCV infection was 6.4% and 9.4%, respectively, with 0.3% co-infection rate. Age, social economic level, history of blood transfusion, history of never using a condom, as well as a history of injury with a used sharp material were significantly associated with HCV infection. CONCLUSION: the study showed a high seroprevalence of both HBV and HCV in Burera´s elderly population aged 45+ years. Several factors associated with HBV and HCV in this study could be prevented through education and improved hygiene.

BackgroundHyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives.MethodsIn a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs).FindingsPravastatin or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD relative to any statin combined with non-RAS-acting AHTs: ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899-0.986, p = 0.011), ACEI+rosuvastatin OR = 0.841 (CI: 0.794-0.892, pConclusionAmong older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.

Despite an array of preventive global public health interventions, SARS-CoV-2 has continued to spread significantly, infecting millions of people across the globe weekly. Newer variants of interest and concern have continued to emerge, placing the need for policymakers to rethink prevention strategies to end the pandemic. The approval of SARS-CoV-2 vaccines for public health use in December 2020 was seen as a significant development towards pandemic control and possibly ending the pandemic. However, breakthrough infections have continued to be observed among the ‘fully vaccinated’, and the duration and sustainability of vaccine-induced immunity has remained a topical public health discourse. In the absence of accurate public health communication, the breakthrough infections and waning immunity concepts have potential to further compound vaccine hesitancy. With this viewpoint, we discuss breakthrough SARS-CoV-2 infections, waning immunity, the need for COVID-19 booster shots, vaccine inequities, and the need to address vaccine hesitancy adequately to propel global vaccination programs forward.

Abstract Milk production in dairy cow udders is a complex and dynamic physiological process that has resisted explanatory modelling thus far. The current standard model, Wood’s model, is empirical in nature, represents yield in daily terms, and was published in 1967. Here, we have developed a dynamic and integrated explanatory model that describes milk yield at the scale of the milking session. Our approach allowed us to formally represent and mathematically relate biological features of known relevance while accounting for stochasticity and conditional elements in the form of explicit hypotheses, which could then be tested and validated using real-life data. Using an explanatory mathematical and biological model to explore a physiological process and pinpoint potential problems (i.e., “problem finding”), it is possible to filter out unimportant variables that can be ignored, retaining only those essential to generating the most realistic model possible. Such modelling efforts are multidisciplinary by necessity. It is also helpful downstream because model results can be compared with observed data, via parameter estimation using maximum likelihood and statistical testing using model residuals. The process in its entirety yields a coherent, robust, and thus repeatable, model.

ObjectiveWe sought to determine patients’ informational needs for post-treatment surveillance and elicit clinicians’ and patient advocates’ (ie, stakeholders) opinions regarding what patients should know about post-treatment surveillance in the USA.DesignA mixed-methods study, using semi-structured interviews followed by a survey study.SettingParticipants for the interviews were from two large academic medical centres and a safety-net hospital. The stakeholders were recruited from attendees at the Alliance for Clinical Trials in Oncology Network Spring 2016 meeting.ParticipantsParticipants for the in-depth interviews were purposively sampled. Eligible patients were 6 months to 5 years post curative resection for colorectal cancer and were fluent in English. Participants for the anonymous survey were stakeholders.Main outcome(s) and measure(s)The main outcome was patients’ with colorectal cancer informational needs for post-treatment surveillance, using an interview guide. The second outcome was the importance of the identified informational needs using an anonymous survey.ResultsOf the 67 patients approached, 31 were interviewed (response rate=46%), the majority were between 1 and 3 years post-treatment (81%) and diagnosed at stage III (74%). Despite a desire to monitor for cancer recurrence, patients had little understanding of the concept of post-treatment surveillance, equating surveillance with screening and a belief that if a recurrence was found early there would be a higher likelihood of cure. The survey suggested that clinicians (n=38) and patient advocates (n=11) had some differing opinions regarding what patients should know about surveillance to be active in decisions. For example, compared with clinicians, patient advocates felt that patients should know recurrence treatment options (100% vs 58%) and likelihood for cure following recurrence treatment (100% vs 38%).ConclusionsThe results of this exploratory mixed-methods study suggest that novel educational interventions targeting both patients and clinicians are needed to address the informational needs for post-treatment surveillance of colorectal cancer.

The role of microbial interactions in defining the properties of microbiota is a topic of key interest in microbial ecology. Microbiota contain hundreds to thousands of operational taxonomic units (OTUs), most of them rare. This feature of community structure can lead to methodological difficulties: simulations have shown that methods for detecting pairwise associations between OTUs, which presumably reflect interactions, yield problematic results. The performance of association detection tools is impaired when there is a high proportion of zeros in OTU tables. Our goal was to understand the impact of OTU rarity on the detection of associations. We explored the utility of common statistics for testing associations; the sensitivity of alternative association measures; and the performance of network inference tools. We found that a large proportion of pairwise associations, especially negative associations, cannot be reliably tested. This constraint could hamper the identification of candidate biological agents that could be used to control rare pathogens. Identifying testable associations could serve as an objective method for filtering datasets in lieu of current empirical approaches. This trimming strategy could significantly reduce the computational time needed to infer networks and network inference quality. Different possibilities for improving the analysis of associations within microbiota are discussed.

Adverse event (AE)-related costs represent an important component of economic models for cancer care. However, since previous studies mostly focused on specific AEs, treatments, or cancer types, limited information is currently available. Therefore, this study assessed the incremental healthcare costs associated with a large number of AEs among patients diagnosed with some of the most prevalent types of cancer. Data were obtained from a large US claims database. Adult patients were included if diagnosed with and treated for one of the following cancer types: breast, digestive organs and peritoneum, genitourinary organs (including bladder and ovary and other uterine adnexa), lung, lymphatic and hematopoietic tissue, and skin. Treatment episodes were defined as the period from initiation of the first antineoplastic pharmacologic therapy to discontinuation (i.e., gap of ≥ 45 days), or change in treatment regimen, or end of data availability. A total of 36 AEs were selected from the product inserts of 104 treatments recommended by practice guidelines. A retrospective matched cohort design was used, matching a treatment episode with a certain AE with a treatment episode without that AE. A total of 412,005 patients were selected, for a total of 794,243 treatment episodes, resulting in 1,617,368 matched treatment episodes across all 36 AEs. Incremental healthcare costs associated with AEs of any severity ranged from $546 for cough/upper respiratory infections to $24,633 for gastrointestinal perforation. The three most costly AEs when considering any severity were gastrointestinal perforation ($24,633), central nervous system hemorrhage ($24,322), and sepsis/septicemia ($23,510). Incremental healthcare costs associated with severe AEs ranged from $15,709 for dermatitis and rash to $48,538 for gastrointestinal fistula. The three most costly severe AEs were gastrointestinal fistula ($48,538), gastrointestinal perforation ($41,281), and central nervous system hemorrhage ($38,428). In conclusion, AEs during treatment episodes for cancer were frequent and associated with a substantial economic burden.

Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide and characterized by the loss of dopaminergic neurons in the patients' midbrains. Both the presence of the protein α-synuclein in intracellular protein aggregates in surviving neurons and the genetic linking of the α-synuclein encoding gene point towards a major role of α-synuclein in PD etiology. The exact pathogenic mechanisms of PD development are not entirely described to date, neither is the specific role of α-synuclein in this context. Previous studies indicate that one aspect of α-synuclein-related cellular toxicity might be direct proteasome impairment. The 20/26S proteasomal machinery is an important instrument of intracellular protein degradation. Thus, direct proteasome impairment by α-synuclein might explain or at least contribute to the formation of intracellular protein aggregates. Therefore this study investigates direct proteasomal impairment by α-synuclein both in vitro using recombinant α-synuclein and isolated proteasomes as well as in living cells. Our experiments demonstrate that the impairment of proteasome activity by α-synuclein is highly dependent upon the cellular background and origin. We show that recombinant α-synuclein oligomers and fibrils scarcely affect 20S proteasome function in vitro, neither does transient α-synuclein expression in U2OS ps 2042 (Ubi(G76V)-GFP) cells. However, stable expression of both wild-type and mutant α-synuclein in dopaminergic SH-SY5Y and PC12 cells results in a prominent impairment of the chymotrypsin-like 20S/26S proteasomal protein cleavage. Thus, our results support the idea that α-synuclein in a specific cellular environment, potentially present in dopaminergic cells, cannot be processed by the proteasome and thus contributes to a selective vulnerability of dopaminergic cells to α-synuclein pathology.

With the rapid extension of clinical data and knowledge, decision making becomes a complex task for manual sleep staging. In this process, there is a need for integrating and analyzing information from heterogeneous data sources with high accuracy. This paper proposes a novel decision support algorithm—Symbolic Fusion for sleep staging application. The proposed algorithm provides high accuracy by combining data from heterogeneous sources, like EEG, EOG and EMG. This algorithm is developed for implementation in portable embedded systems for automatic sleep staging at low complexity and cost. The proposed algorithm proved to be an efficient design support method and achieved up to 76% overall agreement rate on our database of 12 patients.

This paper presents a novel study of logarithmic discrete wavelet transform (DWT) for medical image compression. It proposes a new technique to compute the DWT using the logarithmic number system (LNS) instead of floating point arithmetic. It investigates its impact on the image quality which is an essential factor for medical images to avoid any misdiagnose. The paper presents detailed experimental results for three medical images modalities: CT, MRI and X-Ray. The results show that the LNS approach gives a significant improvement in the image quality measured with the structural similarity index (SSIM).

Human leptospirosis is a zoonotic and potentially fatal disease that has increasingly been reported in both developing and developed countries, including France. However, our understanding of the basic aspects of the epidemiology of this disease, including the source of Leptospira serogroup Australis infections in humans and domestic animals, remains incomplete. We investigated the genetic diversity of Leptospira in 28 species of wildlife other than rats using variable number tandem repeat (VNTR) and multispacer sequence typing (MST). The DNA of pathogenic Leptospira was detected in the kidney tissues of 201 individuals out of 3,738 tested individuals. A wide diversity, including 50 VNTR profiles and 8 MST profiles, was observed. Hedgehogs and mustelid species had the highest risk of being infected (logistic regression, OR = 66.8, CI95% = 30.9-144 and OR = 16.7, CI95% = 8.7-31.8, respectively). Almost all genetic profiles obtained from the hedgehogs were related to Leptospira interrogans Australis, suggesting the latter as a host-adapted bacterium, whereas mustelid species were infected by various genotypes, suggesting their interaction with Leptospira was different. By providing an inventory of the circulating strains of Leptospira and by pointing to hedgehogs as a potential reservoir of L. interrogans Australis, our study advances current knowledge on Leptospira animal carriers, and this information could serve to enhance epidemiological investigations in the future.

In eastern Canada, the destruction of kelp beds by dense aggregations (fronts) of the omnivorous green sea urchin, Strongylocentrotus droebachiensis, is a key determinant of the structure and dynamics of shallow reef communities. Recent studies suggest that hydrodynamic forces, but not sea temperature, determine the strength of urchin-kelp interactions, which deviates from the tenets of the metabolic theory of ecology (MTE). We tested the hypothesis that water temperature can predict short-term kelp bed destruction by S. droebachiensis in calm hydrodynamic environments. Specifically, we experimentally determined relationships among water temperature, body size, and individual feeding in the absence of waves, as well as among wave velocity, season, and aggregative feeding. We quantified variation in kelp-bed boundary dynamics, sea temperature, and wave height over three months at one subtidal site in Newfoundland to test the validity of thermal tipping ranges and regression equations derived from laboratory results. Consistent with the MTE, individual feeding during early summer (June-July) obeyed a non-linear, size- and temperature-dependent relationship: feeding in large urchins was consistently highest and positively correlated with temperature

Lyme borreliosis, one of the most frequently contracted zoonotic diseases in the Northern Hemisphere, is caused by bacteria belonging to different genetic groups within the Borrelia burgdorferi species complex, which are transmitted by ticks among various wildlife reservoirs, such as small mammals and birds. These features make the Borrelia burgdorferi species complex an attractive biological model that can be used to study the diversification and the epidemiology of endemic bacterial pathogens. We investigated the potential of population genomic approaches to study these processes. Sixty-three strains belonging to three species within the Borrelia burgdorferi complex were isolated from questing ticks in Alsace (France), a region where Lyme disease is highly endemic. We first aimed to characterize the degree of genetic isolation among the species sampled. Phylogenetic and coalescent-based analyses revealed clear delineations: there was a ∼50 fold difference between intra-specific and inter-specific recombination rates. We then investigated whether the population genomic data contained information of epidemiological relevance. In phylogenies inferred using most of the genome, conspecific strains did not cluster in clades. These results raise questions about the relevance of different strategies when investigating pathogen epidemiology. For instance, here, both classical analytic approaches and phylodynamic simulations suggested that population sizes and migration rates were higher in B. garinii populations, which are normally associated with birds, than in B. burgdorferi s.s. populations. The phylogenetic analyses of the infection-related ospC gene and its flanking region provided additional support for this finding. Traces of recombination among the B. burgdorferi s.s. lineages and lineages associated with small mammals were found, suggesting that they shared the same hosts. Altogether, these results provide baseline evidence that can be used to formulate hypotheses regarding the host range of B. burgdorferi lineages based on population genomic data.

Latent fingerprint examination is a complex task that, despite advances in image processing, still fundamentally depends on the visual judgments of highly trained human examiners. Fingerprints collected from crime scenes typically contain less information than fingerprints collected under controlled conditions. Specifically, they are often noisy and distorted and may contain only a portion of the total fingerprint area. Expertise in fingerprint comparison, like other forms of perceptual expertise, such as face recognition or aircraft identification, depends on perceptual learning processes that lead to the discovery of features and relations that matter in comparing prints. Relatively little is known about the perceptual processes involved in making comparisons, and even less is known about what characteristics of fingerprint pairs make particular comparisons easy or difficult. We measured expert examiner performance and judgments of difficulty and confidence on a new fingerprint database. We developed a number of quantitative measures of image characteristics and used multiple regression techniques to discover objective predictors of error as well as perceived difficulty and confidence. A number of useful predictors emerged, and these included variables related to image quality metrics, such as intensity and contrast information, as well as measures of information quantity, such as the total fingerprint area. Also included were configural features that fingerprint experts have noted, such as the presence and clarity of global features and fingerprint ridges. Within the constraints of the overall low error rates of experts, a regression model incorporating the derived predictors demonstrated reasonable success in predicting objective difficulty for print pairs, as shown both in goodness of fit measures to the original data set and in a cross validation test. The results indicate the plausibility of using objective image metrics to predict expert performance and subjective assessment of difficulty in fingerprint comparisons.

Models of benthic community dynamics for the extensively studied, shallow rocky ecosystems in eastern Canada emphasize kelp-urchin interactions. These models may bias the perception of factors and processes that structure communities, for they largely overlook the possible contribution of other seaweeds to ecosystem resilience. We examined the persistence of the annual, acidic (H2SO4), brown seaweed Desmarestia viridis in urchin barrens at two sites in Newfoundland (Canada) throughout an entire growth season (February to October). We also compared changes in epifaunal assemblages in D. viridis and other conspicuous canopy-forming seaweeds, the non-acidic conspecific Desmarestia aculeata and kelp Agarum clathratum. We show that D. viridis can form large canopies within the 2-to-8 m depth range that represent a transient community state termed "Desmarestia bed". The annual resurgence of Desmarestia beds and continuous occurrence of D. aculeata and A. clathratum, create biological structure for major recruitment pulses in invertebrate and fish assemblages (e.g. from quasi-absent gastropods to >150,000 recruits kg(-1) D. viridis). Many of these pulses phase with temperature-driven mass release of acid to the environment and die-off in D. viridis. We demonstrate experimentally that the chemical makeup of D. viridis and A. clathratum helps retard urchin grazing compared to D. aculeata and the highly consumed kelp Alaria esculenta. In light of our findings and related studies, we propose fundamental changes to the study of community shifts in shallow, rocky ecosystems in eastern Canada. In particular, we advocate the need to regard certain canopy-forming seaweeds as structuring forces interfering with top-down processes, rather than simple prey for keystone grazers. We also propose a novel, empirical model of ecological interactions for D. viridis. Overall, our study underscores the importance of studying organisms together with cross-scale environmental variability to better understand the factors and processes that shape marine communities.

BackgroundIn natural populations, individuals are infected more often by several pathogens than by just one. In such a context, pathogens can interact. This interaction could modify the probability of infection by subsequent pathogens. Identifying when pathogen associations correspond to biological interactions is a challenge in cross-sectional studies where the sequence of infection cannot be demonstrated.Methodology/principal findingsHere we modelled the probability of an individual being infected by one and then another pathogen, using a probabilistic model and maximum likelihood statistics. Our model was developed to apply to cross-sectional data, vector-borne and persistent pathogens, and to take into account confounding factors. Our modelling approach was more powerful than the commonly used Chi-square test of independence. Our model was applied to detect potential interaction between Borrelia afzelii and Bartonella spp. that infected a bank vole population at 11% and 57% respectively. No interaction was identified.Conclusions/significanceThe modelling approach we proposed is powerful and can identify the direction of potential interaction. Such an approach can be adapted to other types of pathogens, such as non-persistents. The model can be used to identify when co-occurrence patterns correspond to pathogen interactions, which will contribute to understanding how organism communities are assembled and structured. In the long term, the model's capacity to better identify pathogen interactions will improve understanding of infectious risk.

The variation of the composition in species of host communities can modify the risk of disease transmission. In particular, the introduction of a new host species can increase health threats by adding a new reservoir and/or by amplifying the circulation of either exotic or native pathogens. Lyme borreliosis is a multi-host vector-borne disease caused by bacteria belonging to the Borrelia burgdorferi sensu lato complex. It is transmitted by the bite of hard ticks, especially Ixodes ricinus in Europe. Previous studies showed that the Siberian chipmunk, Tamias sibiricus barberi, an introduced ground squirrel in the Forest of Sénart (near Paris, France) was highly infested by I. ricinus, and consequently infected by B. burgdorferi sl. An index of the contribution of chipmunks to the density of infected questing nymphs on the vegetation (i.e., the acarological risk for humans) was compared to that of bank voles (Myodes glareolus) and of wood mice (Apodemus sylvaticus), two known native and sympatric competent reservoir hosts. Chipmunks produced nearly 8.5 times more infected questing nymphs than voles and mice. Furthermore, they contribute to a higher diversity of B. burgdorferi sl genospecies (B. afzelii, B. burgdorferi sensu stricto and B. garinii). The contribution of chipmunks varied between years and seasons, according to tick availability. As T. s. barberi must be a competent reservoir, it should amplify B. burgdorferi sl infection, hence increasing the risk of Lyme borreliosis in humans.

Bone damage removal and callus formation in response to fatigue loading are essential to prevent fractures. Periostin (Postn) is a matricellular protein that mediates adaptive response of cortical bone to loading. Whether and how periostin influences damage and the injury response to fatigue remains unknown. We investigated the skeletal response of Postn(-/-) and Postn(+/+) mice after fatigue stimulus by axial compression of their tibia. In Postn(+/+) mice, cracks number and surface (CsNb, CsS) increased 1h after fatigue, with a decrease in strength compared to non-fatigued tibia. At 15 days, CsNb had started to decline, while CtTV and CtBV increased in fatigued vs non-fatigued tibia, reflecting a woven bone response that was present in 75% of the fatigued bones. Cortical porosity and remodelling also prominently increased in the fatigued tibia of Postn(+/+) mice. At 30 days, paralleling a continuous removal of cortical damage, strength of the fatigued tibia was similar to the non-fatigue tibia. In Postn(-/-) mice, cracks were detectable even in the absence of fatigue, while the amount of collagen crosslinks and tissue hardness was decreased compared to Postn(+/+). Fatigue significantly increased CsNb and CsS in Postn(-/-), but was not associated with changes in CtTV and CtBV, as only 16% of the fatigued bones formed some woven bone. Cortical porosity and remodelling did not increase either after fatigue in Postn(-/-), and the level of damage remained high even after 30 days. As a result, strength remained compromised in Postn(-/-) mice. Contrary to Postn(+/+), which osteocytic lacunae showed a change in the degree of anisotropy (DA) after fatigue, Postn(-/-) showed no DA change. Hence periostin appears to influence bone materials properties, damage accumulation and repair, including local modeling/remodeling processes in response to fatigue. These observations suggest that the level of periostin expression could influence the propensity to fatigue fractures.

Axon injury and degeneration is a common consequence of diverse neurological conditions including multiple sclerosis, traumatic brain injury and spinal cord injury. The molecular events underlying axon degeneration are poorly understood. We have developed a novel method to enrich for axoplasm from rodent optic nerve and characterised the early events in Wallerian degeneration using an unbiased proteomics screen. Our detergent-free method draws axoplasm into a dehydrated hydrogel of the polymer poly(2-hydroxyethyl methacrylate), which is then recovered using centrifugation. This technique is able to recover axonal proteins and significantly deplete glial contamination as confirmed by immunoblotting. We have used iTRAQ to compare axoplasm-enriched samples from naïve vs injured optic nerves, which has revealed a pronounced modulation of proteins associated with the actin cytoskeleton. To confirm the modulation of the actin cytoskeleton in injured axons we focused on the RhoA pathway. Western blotting revealed an augmentation of RhoA and phosphorylated cofilin in axoplasm-enriched samples from injured optic nerve. To investigate the localisation of these components of the RhoA pathway in injured axons we transected axons of primary hippocampal neurons in vitro. We observed an early modulation of filamentous actin with a concomitant redistribution of phosphorylated cofilin in injured axons. At later time-points, RhoA is found to accumulate in axonal swellings and also colocalises with filamentous actin. The actin cytoskeleton is a known sensor of cell viability across multiple eukaryotes, and our results suggest a similar role for the actin cytoskeleton following axon injury. In agreement with other reports, our data also highlights the role of the RhoA pathway in axon degeneration. These findings highlight a previously unexplored area of axon biology, which may open novel avenues to prevent axon degeneration. Our method for isolating CNS axoplasm also represents a new tool to study axon biology.

Following the development of targeted therapies against EGFR and HER2, two members of the human epidermal receptor (HER) family of receptor tyrosine kinases, much interest has been focused on their expression in tumors. However, knowing the expression levels of individual receptors may not be sufficient to predict drug response. Here, we describe the development of antibody-based time-resolved Förster resonance energy transfer (TR-FRET) assays for the comprehensive analysis not only of EGFR and HER2 expression in tumor cryosections, but also of their activation through quantification of HER homo- or heterodimers. First, EGFR and HER2 expression levels were quantified in 18 breast tumors and the results were compared with those obtained by using reference methods. The EGFR number per cell determined by TR-FRET was significantly correlated with EGFR mRNA copy number (P

Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured unsystematically while following a baboon troop, while others were designed to vary a single parameter such as aperture, object distance, time of day or position on the horizon. Images are available in the raw RGB format and in grayscale. Images are also available in units relevant to the physiology of human cone photoreceptors, where pixel values represent the expected number of photoisomerizations per second for cones sensitive to long (L), medium (M) and short (S) wavelengths. This database is distributed under a Creative Commons Attribution-Noncommercial Unported license to facilitate research in computer vision, psychophysics of perception, and visual neuroscience.

In occupational health and safety literature, supporters of the systemic approach and those of the behavioral approach are often presented as belonging to two opposing camps. Each group, with research to back it up, attempts to demonstrate its ability to prevent and reduce accident rates within organizations. This article presents the difficulties and effects of using a peer-based behavior observation process in a manufacturing setting that already had a well-structured OHS program. This case study is based on field observations, a review of available documents (policies, meeting reports, and detailed statistics, etc.) and twenty semi-structured interviews with individuals involved in OHS activities. The results suggest that the two approaches were not incompatible but that their relationship was not problem-free. We noticed in particular that a lack of clarity in role definitions sometimes led to conflicts between the groups in charge of their management. Moreover, behavior observation by peers had some definite advantages according to the respondents. It was perceived as a useful tool for making workers more aware of, involved in and responsible for OHS, which would make it an interesting complement to the systemic approach. To this end, we noted a positive correlation between the frequency of observation sessions and the number of incidents reported by workers. The corrections made after the reports subsequently reduced system-related risks. Consequently, a program initially designed to modify behavior had effects that went beyond the original intention. The behavior observation process was a delicate one. There were difficulties related to freeing up and training observers, to organizing the committee in charge of the process, and to establishing harmonious relations with the organization’s OHS committee.