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To address community-driven concerns about lead-contaminated drinking water in residential homes in the Greater Fifth Ward neighborhood in Northeast Houston, Texas utilizing participatory-based research. The study collected survey data and performed lead analysis on drinking water from residents’ homes. The Greater Fifth Ward is characterized as a majority-minority environmental justice community and is located within two confirmed cancer clusters. The residents of 172 homes completed a survey and had detectable lead levels in their water samples. Survey results indicated that more than half of the residents (58.2%) were concerned with the water quality and 42.9% rated the drinking water as poor. Water lead levels detected ranged from 0.01 to 22 µg/L. 10.9% of homes exceeding 1 µg/L, and one located exceeded the USEPA’s action limit of 15 µg/L. Homes built prior to 1978 without major renovation had significantly higher levels of lead in their drinking water compared to homes built after 1978 (p-value < 0.05). These findings demonstrate the need for lead testing of residential water in low socioeconomic-status communities, as well as demonstrating the benefits of community engagement and participatory research to address environmental health concerns.

Breast feathers of Neotropic Cormorants (Phalacrocorax brasilianus) from two nesting colonies in Lake Livingston (LALIV) and Richland Creek, Texas, were collected during 2014 and were analyzed for metals and metalloids. Mean concentrations of Al, As, Cr, Cu, Fe, Pb, Sb, and Se were not significantly different in breast feathers of cormorants from the two locations or between sexes. However, mean concentrations of Co, Mn, Ni, and V were significantly greater in feathers of cormorants from Richland Creek than in those from LALIV; and Zn concentrations were greater in cormorants from LALIV than in those from Richland Creek (p

Introduction Historically, there were concerns vasopressors impair free flap outcomes, but recent studies suggest vasopressors are safe. Here we investigate this controversy by (1) evaluating vasopressors' effect on head and neck free-flap survival and surgical complications, and (2) performing soft tissue and bony subset analysis. Patients and methods Post hoc analysis was performed of a single-blinded, prospective, randomized clinical trial at a tertiary care academic medical center involving patients ≥18 years old undergoing head and neck free flap reconstruction over a 16-month period. Patients were excluded if factors prevented accurate FloTrac™ use. Patients were randomized to traditional volume-based support, or goal-directed support including vasopressor use. Primary data was obtained by study personnel through intraoperative data recording and postoperative medical record review. Results Forty-one and 38 patients were randomized to traditional and pressor-based algorithms, respectively. Flap survival was 95% (75/79). There was no significant difference between the pressor-based and traditional protocols' flap failure (1/38 [3%] vs. 3/41 [7%], RR 0.36, 95% CI of RR 0.04-3.31, p = .63) or flap-related complications (12/38 [32%] vs. 18/41 [44%], RR 0.72, 95% CI 0.40-1.29, p = .36) Soft tissue flaps had surgical complication rates of 12/30 (40%) and 9/27 (33%) for traditional and pressor-based protocols, respectively. Bony flaps had surgical complication rates of 6/11 (55%), and 3/11 (27%) for traditional and pressor-based protocols, respectively. Conclusions Intraoperative goal-directed vasopressor administration during head and neck free flap reconstruction does not appear to increase the rate of flap complications or failures.

This paper provides a description of the MyCap data collection platform, utilization metrics, and vignettes associated with use from diverse research institutions. MyCap is a participant-facing mobile application for survey data collection and the automated administration of active tasks (activities performed by participants using mobile device sensors under semi-controlled conditions). Launched in 2018, MyCap is a no-code solution for research teams conducting longitudinal studies, integrates tightly with REDCap and is available at no cost to research teams at academic, nonprofit, or government organizations. MyCap has been deployed at multiple research institutions with application usage logged across 135 countries in 2021. Vignettes demonstrate that MyCap empowered research teams to explore and implement novel methods of information collection and use. MyCap’s integration with REDCap provides a comprehensive data collection ecosystem and is best suited for longitudinal studies with frequent requests for information from participants.

BackgroundThe burden of many infectious diseases varies seasonally and a better understanding of the drivers of infectious disease seasonality would help to improve public health interventions. For directly transmitted highly-immunizing childhood infections, the leading hypothesis is that seasonality is strongly driven by social gatherings imposed by schools, with maxima and minima during school terms and holidays respectively. However, we currently have a poor understanding of the seasonality of childhood infections in societies without schools and whether these are driven by human social gatherings. Here, we used unique nationwide data consisting of >40 epidemics over 100 years in 18th and 19th century Finland, an agricultural pre-health care society without schools, to (i) quantify the seasonality of three easily identifiable childhood infections, smallpox, pertussis and measles and (ii) test the extent to which seasonality of these diseases is driven by seasonal social gatherings.MethodsWe quantified the seasonality of transmission using time series Susceptible-Infected-Recovery models, wavelet analyses and general additive mixed models.ResultsWe found that all three infections were seasonal and the seasonality patterns differed from those in industrialized societies with schools. Smallpox and measles showed high transmission in the first half of the year, but we could not associate this with seasonal human gatherings events. For pertussis, however, transmission was higher during social gathering events such as New Year and Easter.ConclusionsOur results show that the seasonality of childhood infections is more variable than previously described in other populations and indicate a pathogen-specific role of human social aggregation in driving the infectious disease dynamics.FundingAcademy of Finland (278751, 292368), Nordforsk (104910), the Ehrnrooth Foundation, the Finnish Cultural Foundation, the University of Turku Foundation and the Doctoral Programme in Biology, Geography and Geology, University of Turku.Clinical trial numberNA

In a health emergency, clear, two-way communication between researchers and a broad spectrum of stakeholders is essential to establishing trust—a prerequisite for meaningful uptake of new treatments and vaccines.

Introduction Prior studies found renal disease was common among HIV-infected outpatients. We updated incident renal disease estimates in this population, comparing those with and without tenofovir exposure. Methods We conducted a retrospective analysis of the DC Cohort, a longitudinal study of HIV patients in Washington, DC, from 2011 to 2015. We included adults prescribed antiretroviral therapy (ART) with baseline glomerular filtration rate (GFR) ≥15 ml/min per 1.73 m2. We defined renal disease as 50% decrease in GFR or doubled serum creatinine (Cr) within 3 months. We defined cumulative viral load as area under the curve (AUC) of log10 transformed longitudinal HIV RNA viral load (VL). Correlates of time to incident renal disease were identified using Cox proportional hazard regression models, adjusted for demographics and known risk factors for kidney disease. Results Among 6068 adults, 77% were Black and median age was 48 years. Incident renal disease rate was 0.77 per 100 person-years (95% confidence interval [CI]: 0.65–0.9). Factors associated with renal disease were age (adjusted hazard ratio [aHR]: 1.4; CI 1.1–1.7 per 10 years), public non-Medicaid, non-Medicare insurance (aHR: 3.4; CI: 1.9–6.4), AUC VL (aHR: 1.1; CI: 1.1–1.2), diabetes mellitus (aHR: 1.6; CI: 1.0–2.4), and mildly reduced GFR (60–89 ml/min per 1.73 m2) (aHR: 1.5; CI: 1.0–2.3); recent tenofovir exposure was not associated with renal disease (aHR: 0.7; CI: 0.5–1.1). Conclusion Our study revealed a substantial burden of renal disease among HIV patients. Cumulative VL was associated with renal disease, suggesting that early VL suppression may decrease its incidence., Graphical abstract

As industrial development, aerial deposition of pollutants, and chemical releases from thawing permafrost increase in the Arctic, there is need to monitor exposure to contaminants in a range of species. Surrogate or bioindicator species are often used to represent groups of taxa and are typically selected for their wide geographic ranges and ease of sampling. However, it is seldom known how well surrogates exemplify different species, ages, or breeding stages in different areas. We examined multiple trace elements in incubating females of five sea duck species (long-tailed ducks Clangula hyemalis, Steller’s eiders Polysticta stelleri, spectacled eiders Somateria fischeri, king eiders S. spectabilis, and common eiders S. mollissima), in pre-laying spectacled eiders, and in brood-rearing female spectacled and king eiders and their ducklings, among four areas on the Arctic Coastal Plain of Alaska, USA. For Se, Cd, and Cu that are probably acquired during the nonbreeding period, Se and Cd in the blood of hens varied appreciably among species, whereas all species appeared to regulate Cu at similar concentrations. Levels of blood Hg and Pb sampled during incubation were inconsistent among species, apparently reflecting variable exposure on breeding areas. During incubation, species of similar body mass had similar patterns of elements. Se, Cu, and Pb differed substantially across the breeding season in spectacled eiders, as well as between ducklings and hens of spectacled and king eiders. Although analysis of feathers avoids invasive sampling, patterns of element concentrations in feathers differed from those in blood. Species of comparable body mass and life history traits sampled at a given site generally had similar concentrations of trace elements in blood, suggesting some utility as surrogates, but still showed regional variation. Our results suggest that for sea ducks, surrogate species of varying body mass and life history traits may not consistently reflect levels of exposure across taxa, or even among congeners or sex-age classes in the same areas. Biomonitoring for contaminants should use species of comparable mass as indicators at small spatial scales, but at the regional scale, should focus on specific taxa of concern.

BACKGROUND: The European Centres for Disease Prevention and Control (ECDC) estimates that seasonal influenza causes 4-50 million symptomatic infections in the EU/EEA each year and 15,000-70,000 European citizens die of causes associated with influenza. We used modelling methods to estimate influenza-associated mortality for the European Union by age group and country. METHODS: We compiled influenza-associated respiratory mortality estimates for 31 countries around the world (11 countries in the EU) during 2002-2011 (excluding the 2009 pandemic). From these we extrapolated the influenza mortality burden for all 193 countries of the world, including the 28 countries of the EU, using a multiple imputation approach. To study the effect of vaccination programs, we obtained data from the EU-funded VENICE project regarding the percentage of persons over 65 who were vaccinated in each country; the data ranged from 2% to 82% between the 21 countries which provided estimates for the 2006/07 reference season. RESULTS: We estimated that an average of 27,600 (range 16,200-39,000) respiratory deaths were associated with seasonal influenza in the 28 EU countries per winter; 88% were among people 65 years and older, and the rates of mortality in this age group were roughly 35 times higher compared with those

Introduction At the population level, Black and Hispanic adults in the United States have increased risk of dying from COVID-19, yet whether race and ethnicity impact on risk of mortality among those hospitalized for COVID-19 is unclear. Methods Retrospective cohort study using data on adults hospitalized with COVID-19 from the electronic health record from 52 health systems across the United States contributing data to Cerner Real World DataTM. In-hospital mortality was evaluated by race first in unadjusted analysis then sequentially adjusting for demographics and clinical characteristics using logistic regression. Results Through August 2020, 19,584 patients with median age 52 years were hospitalized with COVID-19, including n = 4,215 (21.5%) Black and n = 5,761 (29.4%) Hispanic patients. Relative to white patients, crude mortality was slightly higher in Black adults [22.7% vs 20.8%, unadjusted OR 1.12 (95% CI 1.02–1.22)]. Mortality remained higher among Black adults after adjusting for demographic factors including age, sex, date, region, and insurance status (OR 1.13, 95% CI 1.01–1.27), but not after including comorbidities and body mass index (OR 1.07, 95% CI 0.93–1.23). Compared with non-Hispanic patients, Hispanic patients had lower mortality both in unadjusted and adjusted models [mortality 12.7 vs 25.0%, unadjusted OR 0.44(95% CI 0.40–0.48), fully adjusted OR 0.71 (95% CI 0.59–0.86)]. Discussion In this large, multicenter, EHR-based analysis, Black adults hospitalized with COVID-19 had higher observed mortality than white patients due to a higher burden of comorbidities in Black adults. In contrast, Hispanic ethnicity was associated with lower mortality, even in fully adjusted models.

BackgroundThe draconian measures used to control COVID-19 dissemination have been highly effective but only at enormous socioeconomic cost. Evidence suggests that “superspreaders” who transmit the virus to a large number of people, play a substantial role in transmission; recent estimates suggest that about 1-20% of people with the virus are the source for about 80% of infections. We used an agent-based model to explore the interplay between social structure, mitigation and superspreading.MethodsWe developed an agent-based model with a subset of “superspreader” agents that transmit disease far more efficiently. These agents act in a social network that allows transmission during contacts in three sectors: “home,” “work/school” and “other”. We simulated the effect of various mitigation strategies that limit contacts in each of these sectors, and used the model to fit COVID-19 mortality data from Sweden.FindingsReducing contacts in the “other” sector had a far greater impact on epidemic trajectory than did reducing “home” or “work/school” contacts; this effect was substantially enhanced when the infectivity of children was reduced relative to that of adults. The model fit Swedish hospitalization data with reasonable assumptions about the effect of Sweden’s mitigation policies on contacts in the different sectors.InterpretationOur results suggest COVID-19 could be controlled by limiting large gatherings and other opportunities for contacts between people in restaurants, sporting events, concerts and worship services) while still allowing regular contacts in the home or at work and school.Research in contextEvidence before this studySuperspreading events have long been known to be important in the epidemiology of many infectious diseases, including tuberculosis, measles, Ebola and SARS. Since the emergence of SARS-CoV-2, epidemiologic analyses have inferred substantial individual-level variation in transmissibility, with an estimated 1% to 20% of infected persons causing about 80% of all COVID-19 cases.Added value of this studyWe developed an agent-based socially structured model to simulate the effect of superspreaders in COVID-19 transmission in the context of country-wide “lockdown” policies. These simulations indicate that COVID-19 can be effectively mitigated by limiting contacts between people who otherwise rarely meet, while allowing home and most work/school contacts to continue.Implications of all available evidenceIt is crucial to include heterogeneity in individual infectiousness when modeling the impact of mitigation strategies on observed COVID-19 epidemic patterns. Reducing opportunities for superspreading by limiting random contacts outside home and work could be the most effective way to control COVID-19. Our findings suggest why the epidemic has continued to decline following re-opening of work and school in European countries. The superspreader phenomenon may also explain the variability in COVID-19 incidence in rural and urban areas within a country.

Background In several inflammatory disorders, altered peripheral blood mononuclear leukocyte (PBML) glucocorticoid (GC) receptor isoform expression has been associated with GC resistance and disease severity. However, it is unclear if PBML GC receptor isoforms are expressed differentially and are associated with worsened disease severity in chronic rhinosinusitis (CRS). Methods PBMLs were isolated from control (n = 8), CRS without nasal polyps (CRSsNP) (n = 8), atopic CRS with nasal polyps (CRSwNP) (n = 8), non-atopic CRSwNP (n = 8), and allergic fungal rhinosinusitis (AFRS) (n = 8) patients. Demographics, atopic status, asthmatic status, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, Lund-Kennedy nasal endoscopy scores, Lund-Mackay sinus computed tomography (CT) scores, Kennedy Osteitis scores, and GC utilization 6 months postoperatively were collected. Intracellular immunostaining was then performed for functional GC receptor α (GCRα) and nonfunctional GC receptor β (GCRβ), followed by flow cytometry analysis of geometric mean fluorescent intensity (MFI) and the percentage of cells expressing each GC receptor isoform. Results Compared to controls, each CRS subtype had decreased PBML GCRα and GCRα:GCRβ MFI expression, but no difference in GCRβ expression. Decreasing PBML GCRα in AFRS was associated with increasing Lund-Mackay sinus CT scores (r = -0.880, p =0.004). No significant associations were found between GC receptor isoform expression and other clinical measures. Conclusion CRS patients have reduced functional PBML GCRα expression and decreased GCRα:GCRβ compared to controls. Reductions in GCRα in AFRS are associated with worsening Lund-Mackay sinus CT scores. The clinical implications of decreased functional GC receptor expression merits further investigation.

The control loop stability in boost converters operating in continuous conduction mode has been restricted due to its nonminimum phase nature: the presence of a positive zero (right-half plane zero) in the control to output voltage transfer function. This paper proposes a method to mitigate the effect of the zero on the control loop by shifting the position of the zero to the left-half plane and hence leading to increased stability for the control loop of the boost converter. Superior performance of the proposed method has been clearly demonstrated using simulation and experimental results.

Northern bobwhites (Colinus virginianus) have been declining across the range of the species primarily due to habitat loss and habitat fragmentation. There is increasing concern regarding effects related to elevated environmental contaminants, including pesticides and metals. Elevated concentrations of some metals are known to have adverse effects on reproduction, development, and survival in birds; however, little research has been conducted on metal exposure in wild bobwhites. We analyzed metal concentrations in the feathers of 60 bobwhites from 3 ecoregions in Texas and evaluated differences between age-class, gender, and location with the objective of determining if bobwhites in Texas are at increased risk of exposure to elevated metal concentrations. We found feather Pb concentrations above the established effect threshold of 4.0 µg/g dry weight at which sublethal and reproductive effects have been reported in birds. More than 25% (n = 16) of the samples analyzed had Pb concentrations above the effect threshold, including four that were five times above the threshold. We also observed slightly elevated feather Cd concentrations, above 0.1 µg/g dry weight, in 17% (n = 11) of the bobwhites analyzed. On average, juvenile bobwhites had higher concentrations of Ba, Co, Fe, Mn, Sr, and V compared to adults (p

Environmental contamination with hexavalent chromium (CrVI) is a growing problem both in the United States and developing countries. Hexavalent chromium is widely used in numerous industries. Environmental exposure to CrVI adversely affects pregnancy outcomes and subsequent health of 2 generations, resulting in higher pregnancy loss, spontaneous abortion and low birth rate. Pregnant women exposed to CrVI through occupational settings experience increased risk of spontaneous abortion, stillbirth, preterm birth, and neonatal death. Children of the CrVI exposed women experience respiratory problems, perinatal jaundice, and increased birth defects. Because placental dysfunction may have a role in such adverse pregnancy outcome, we tested the hypothesis that environmental Cr exposure in pregnant women results in Cr accumulation in the human placenta, which could increase placental oxidative stress by disrupting antioxidant machinery and inducing apoptosis. Studies using frozen, deidentified human term placenta samples indicated that: (1) Cr accumulates in human term placenta tissues and (2) increase in Cr accumulation is positively correlated with oxidative stress and apoptotic markers, and altered antioxidants levels. Interestingly, there was a sexual dimorphism in the correlation between Cr accumulation and oxidative stress, and expression of apoptotic and antioxidant markers. Mechanistic in vitro studies using human trophoblast cells BeWo confirmed the detrimental effects of Cr in altering antioxidant genes. For the first time, this study provides evidence in support of a positive correlation between Cr accumulation in the human placenta and accelerated oxidative stress, with a gender bias toward the male sex.

To investigate the epidemiology, treatment, length of stay (LOS) and costs for neonatal and pediatric inpatients with invasive candidiasis (IC).The Cerner Health Facts Database was used to assess inpatients (2005-2014) identified by positive blood or cerebrospinal fluid (CSF) Candida cultures. Log-transformed LOS and cost were examined in candidemia-only patients (n = 191) using multivariable linear regression.A total of 202 patients had a positive culture (blood: n = 192; CSF: n = 10; both: n = 2). The most prevalent species were C. parapsilosis (n = 70, 34.7%), and C. albicans (n = 66, 32.7%). Mean (SD) age was 5 (5.5) years; 30 (14.9%) patients were4 months. Comorbidities included sepsis (n = 85, 42.1%), coagulation disorders (n = 57, 28.2%), cancer (n = 64, 31.7%), and low birthweight (n = 26, 12.9%). Antifungals (AFs) included azoles (57.4%), polyenes (28.7%), and echinocandins (35.1%); 20.8% of patients received no AF during their encounter. The mean (SD) cost per encounter was $97,392 ($149,253), with a mean (SD) LOS of 45.6 (59.5) days and 9.9% mortality at discharge. Results were similar across Candida species. In regression analysis, intensive care unit (ICU) exposure, central catheter, sepsis, AF48 hours prior to index culture, and age4 months were associated with increased LOS; treatment at a non-teaching hospital was associated with reduced LOS (p .05). AF use48 hours before index, in-hospital mortality, Midwest region and ventricular shunt were associated with increased cost (p ≤ .05).This analysis confirms the association between pediatric candidemia and increased resource utilization and LOS. Given high observed rates of potential under-treatment, an opportunity may exist to improve AF therapy in this population.

This brief presents the analysis of zeros present in boost dc–dc converters that are operating in continuous inductor current mode. It proposes the utilization of the concept of multiple forward pathways from input to output to analyze the origin of the resulting zeros and determine their locations. This brief provides insight into the various zeros present in the boost converter through a state diagram approach.

We compared total mercury (Hg) concentrations in whole blood of harlequin ducks (Histrionicus histrionicus) sampled within and among two geographically distinct locations and across three years in southwest Alaska. Blue mussels were collected to assess correlation between Hg concentrations in locally available forage and birds. Mercury concentrations in harlequin duck blood were significantly higher at Unalaska Island (0.31 ± 0.19 mean ± SD, μg/g blood) than Kodiak Island (0.04 ± 0.02 mean ± SD, μg/g blood). We found no evidence for annual variation in blood Hg concentration between years at Unalaska Island. However, blood Hg concentration did vary among specific sampling locations (i.e., bays) at Unalaska Island. Findings from this study demonstrate harlequin ducks are exposed to environmental sources of Hg, and whole blood Hg concentrations are associated with their local food source.

Background Estimates of influenza and respiratory syncytial virus (RSV) burden must be periodically updated to inform public health strategies. We estimated seasonal influenza- and RSV-attributable hospitalizations in the US from 1997 to 2009 according to age and risk status (NCT01599390). Methods Multiple linear regression modelling was used to attribute hospitalizations to influenza or RSV using virological surveillance and hospitalization data. Hospitalization data were obtained from the US Nationwide Inpatient Sample and virology data were obtained from FluView (Centers for Disease Control and Prevention). Outcomes included any mention of ICD-coded respiratory disease and cardiorespiratory disease diagnoses. We also explored a broader definition of respiratory disease that included mention of relevant respiratory sign/symptoms and viral infection (“respiratory broad”). Results Applying the respiratory broad outcome, our model attributed ~300,000 and ~200,000 hospitalizations to influenza and RSV, respectively. Influenza A/H3N2 was the predominant cause of influenza-related hospitalizations in most seasons, except in three seasons when influenza B was dominant; likewise, A/H3N2 caused most influenza-related hospitalizations in all age segments, except in children

Environmental contamination with hexavalent chromium (CrVI) is a growing problem both in the U.S and developing countries. CrVI is a heavy-metal endocrine disruptor; women working in Cr industries exhibit an increased incidence of premature abortion and infertility. The current study was designed to understand the mechanism of CrVI toxicity on placental cell survival/death pathways. Pregnant mothers were treated with or without CrVI (50 ppm K 2 Cr 2 O 7 ) through drinking water from gestational day (GD) 9.5–14.5, and placentas were analyzed on GD 18.5. Results indicated that CrVI increased apoptosis of trophoblasts, vascular endothelium of the metrial glands and yolk sac epithelium through caspase-3 and p53-dependent pathways. CrVI increased apoptosis in labyrinth and basal zones in a caspase-3-independent manner via AIF, and through an ATM-p53-NOXA-PUMA-p27 network. CrVI downregulated cell survival proteins Bcl-2, Bcl-XL and XIAP in the placenta. CrVI disrupts placental histoarchitecture and increases cell death by spatiotemporal modulation of apoptotic signaling.

We developed a simple method of analyzing the strontium (Sr) and calcium (Ca) content of intact eggshell samples in support of a broader study of how dietary Sr uptake impacts waterfowl eggshell quality. We used wavelength dispersive - x-ray fluorescence spectrometry (WD-XRF) to analyze eggshell pieces ranging in size from ∼6-mm2 fragments to intact half-shells. We verified this approach on a subset of reference shells by subjecting the same region and volume of shell material from which x-ray signals were measured to analysis by inductively-coupled plasma mass spectrometry (ICP-MS). An analysis of the sources of analytical uncertainty yielded total internal error estimates of ±0.3 and 5% relative for Ca and Sr, respectively, on the basis of which the chemistry of intact shell material analyzed by WD-XRF in this study is compared. The total external errors associated with the WD-XRF results of this study in relation to certified reference material (National Institute of Standards and Technology [NIST] 1400 [a bone ash]) are ±9 and 13.5% relative for Ca and Sr, respectfully (95% CL). Our results demonstrate this method is acceptably accurate and precise for many wildlife management applications. WD-XRF analysis is a quick and inexpensive alternative to traditional methods for determining eggshell Sr and Ca that require acid digestion, allowing for generation of larger datasets that might otherwise be cost-prohibitive, while preserving sample material intact.

Chronic wounds are projected to reach epidemic proportions worldwide because of the aging population and the increasing incidence of diabetes. Despite extensive research, infection remains one of the leading sources of complications in chronic wounds, resulting in improper healing, biofilm formation, and lower extremity amputation. To address the limitations of standard treatments, we have developed a hydrogel wound dressing with self-tuning moisture control that incorporates a novel antimicrobial agent to eliminate and prevent infection. 3D-printing of a hydrogel dressing with dual porosity resulted in a new dressing with greater flexibility, increased water uptake, and more rapid swelling than bulk hydrogel dressings. Additionally, gallium maltolate (GaM) was incorporated into the dressing to investigate the efficacy of this antimicrobial agent. Loading profiles, release kinetics, and the bactericidal activity against Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) of GaM were investigated in vitro to identify target profiles that supported infection control. Finally, GaM-loaded hydrogel dressings were evaluated in vivo, utilizing a murine splinted-wound model that was inoculated with S. aureus. In comparison to an untreated control, GaM dressings markedly reduced the wound bacterial load without compromising wound closure rates. Overall, this work demonstrates the utility of a 3D-printed hydrogel dressing as an antimicrobial dressing to control infection in chronic wounds.

BACKGROUND: In 2009, Gavi, the World Bank, and donors launched the pneumococcal Advance Market Commitment, which helped countries access more affordable pneumococcal vaccines. As many low-income countries begin to reach the threshold at which countries transition from Gavi support to self-financing (3-year average gross national income per capita of US$1580), they will need to consider whether to continue pneumococcal conjugate vaccine (PCV) use at full cost or to discontinue PCV in their childhood immunisation programmes. Using Kenya as a case study, we assessed the incremental cost-effectiveness of continuing PCV use. METHODS: In this modelling and cost-effectiveness study, we fitted a dynamic compartmental model of pneumococcal carriage to annual carriage prevalence surveys and invasive pneumococcal disease (IPD) incidence in Kilifi, Kenya. We predicted disease incidence and related mortality for either continuing PCV use beyond 2022, the start of Kenya's transition from Gavi support, or its discontinuation. We calculated the costs per disability-adjusted life-year (DALY) averted and associated 95% prediction intervals (PI). FINDINGS: We predicted that if PCV use is discontinued in Kenya in 2022, overall IPD incidence will increase from 8·5 per 100 000 in 2022, to 16·2 per 100 000 per year in 2032. Continuing vaccination would prevent 14 329 (95% PI 6130–25 256) deaths and 101 513 (4386–196 674) disease cases during that time. Continuing PCV after 2022 will require an estimated additional US$15·8 million annually compared with discontinuing vaccination. We predicted that the incremental cost per DALY averted of continuing PCV would be $153 (95% PI 70–411) in 2032. INTERPRETATION: Continuing PCV use is essential to sustain its health gains. Based on the Kenyan GDP per capita of $1445, and in comparison to other vaccines, continued PCV use at full costs is cost-effective (on the basis of the assumption that any reduction in disease will translate to a reduction in mortality). Although affordability is likely to be a concern, our findings support an expansion of the vaccine budget in Kenya. FUNDING: Wellcome Trust and Gavi, the Vaccine Alliance.

Objective It is important to characterize the developing complication profile of the open approach as it becomes reserved for more complex disease during the endoscopic era. Our objective was to characterize complication rates of current open skull base surgery. Design Retrospective chart review. Setting Tertiary care center. Participants The study group consisted of 103 patients and 117 open skull base surgeries were performed from 2008 to 2012. Main Outcome Measures Intraoperative/postoperative complications. Methods Fisher exact test and Wilcoxon rank sum test evaluated for associations of complications with potential risk factors. Results Postoperative complications occurred in 53 (45%) cases, of which 36 (31%) were major complications. Malignancy, dural grafting, age, and obesity were not associated with complications. Flap reconstruction was associated with increased complication rates (odds ratio = 2.27; 95% confidence interval: 1.03–5.04). Conclusion The open approach is increasingly utilized for only the most complex lesions, and selection bias cannot be overstated in comparative series. This study suggests that current open complication rates may be above those cited from prior studies, and patient and physician expectations should be adjusted accordingly.

The mobilization of co-occurring trace elements (CTEs) in aquifers with known metal(loid) contamination may exacerbate potential human health threats where release mechanisms are not geochemically limited. This study investigates the co-mobilization of the potentially toxic CTEs antimony (Sb), molybdenum (Mo), vanadium (V), uranium (U), and selenium (Se) with arsenic (As) and iron (Fe) in contrasting high and low As aquifers surrounding the river Bhagirathi in Murshidabad, West Bengal, India. We sought to determine the dominant release mechanisms and fate of each CTEs as they relate to redox conditions, major element dissolution pathways, and characteristics of dissolved organic matter (DOM). Groundwater samples collected in 2013 and 2015 field campaigns across six villages in the Murshidabad district were analyzed for major and trace elements, as well as the quantity and optical properties of DOM. East of the river Bhagirathi, the Holocene aquifer contained groundwater with compositions reflective of carbonate mineral dissolution and silicate mineral weathering, along with clear signs of Fe reduction and associated mobilization of As, Sb, Mo, V, and U. Relatively oxic groundwater in the Pleistocene aquifer underlying the study sites on the west side of the river showed minimal Fe reduction and signatures of carbonate mineral dissolution and silicate mineral weathering (i.e., Nabagram), or evaporite mineral dissolution (i.e., Kandi). In groundwater samples from the more oxic Pleistocene aquifer, concentrations of As, Sb, Mo, and V were substantially lower than in the Holocene aquifer, however, U concentrations were relatively higher where carbonate mineral dissolution predominated (i.e., Nabagram). Compelling positive correlations between Fe and CTEs in the Holocene but not in the Pleistocene aquifer implicated Fe reductive processes as the probable pathway for CTEs release. The presence of humic-like DOM ligands and inorganic ions (i.e., Ca2+, CO32−) may also enhance CTEs mobility via aqueous complexation reactions, or possibly by inhibiting CTEs adsorption. We further hypothesize that carbonate mineral dissolution mobilizes U in the absence of Fe reduction, and that U solubility in the reducing Holocene aquifer may be facilitated by carbonate mineral dissolution products (e.g., Ca2+, HCO3−, CO32−) that promote U complexation and the inhibition of (bio)immobilization pathways. Conclusively, potentially toxic CTEs are being mobilized concomitantly with As in the Murshidabad district of West Bengal, probably by microbial Fe reduction. Because these aquifers still contain requisite organic matter and bulk sediment Fe required for Fe reductive processes, it follows that concentrations of CTEs may increase in the future. We therefore argue that despite moderately low concentrations of CTEs in the current study, mechanistic modeling efforts and more extensive monitoring of trace metal(loid)s should be performed to ensure that drinking water supplies do not pose additional health threats in the coming years.

Supplemental Digital Content is available in the text., Background: The synthetic control model is a powerful tool to quantify the population-level impact of vaccines because it can adjust for trends unrelated to vaccination using a composite of control diseases. Because vaccine impact studies are often conducted using smaller, subnational datasets, we evaluated the performance of synthetic control models with sparse time series data. To obtain more robust estimates of vaccine impacts from noisy time series, we proposed a possible alternative approach, STL+PCA method (seasonal-trend decomposition plus principal component analysis), which first extracts smoothed trends from the control time series and uses them to adjust the outcome. Methods: Using both the synthetic control and STL+PCA models, we estimated the impact of 10-valent pneumococcal conjugate vaccine on pneumonia hospitalizations among cases

Background: Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response.Methods: We estimated the CFR of medically attended influenza (CFRMA) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009-2011) and post-pandemic (2012-2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFRAR).Results: During the pandemic period, 5.0% (3.1%-6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive inpatients, 8.5% (5.7%-12.6%) died. CFRMA for pH1N1 was 0.4% (0.2%-0.6%) in the pandemic period 2009-2011 but declined 5-fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period 2012-2015. CFR for influenza-negative patients did not change over time. We estimated the 2009 pandemic CFRAR to be 0.025%, 16-fold lower than CFRMA.Conclusions: Data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. Going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity.Clinical Trials Registration: NCT01056354 and NCT010561.

Background The cribriform plate (CP) is a common site of spontaneous cerebrospinal fluid (SCSF) leaks. Radiographic assessment of the anterior and lateral skull base has shown thinner bone in patients with SCSFs; however, prior assessment of the CP has required postmortem cadaver dissection. Objective To develop novel radiographic techniques to assess the anatomy of the CP. Methods Computed tomography (CT) scans were performed on cadaveric specimens. Bone density and anatomy of a predefined volume of interest of the posterior CP were assessed by two independent reviewers. CT assessment of olfactory foramina was also performed and validated using anatomic dissection of cadaver specimens. Results Interclass correlation coefficients (ICCs) for measuring the same volume of each CP was 0.96, confirming reproducible anatomic localization. Cadaver CPs had a mean Hounsfield units of 263, indicating a mix of bone and soft tissue, and ICC was 0.98, confirming reproducible radiographic measurements. Optimal CT estimates of bone composition of CPs averaged 85% (range 76% to 96%) compared to actual anatomic dissection which averaged 84% bone (range 74% to 91%, r = .690, P = .026). Conclusion Our novel, noninvasive CT method for assessing CP anatomy is reproducible and correlates with anatomic dissection assessing bone composition. The clinical implications of anatomic changes in the CP are an area for further study.

Objective We report an association between lower cranial nerve (CN IX/X) vascular compression at the brainstem with laryngeal symptoms utilizing a stepwise algorithm that systematically evaluates and eliminates all other common etiologies. Our experiences with retromastoid craniectomy with lower cranial nerve (LCN) decompression versus non-neurosurgical treatments are detailed. Study design Retrospective chart review at a tertiary care academic medical center with follow-up telephone survey. Methods Baseline demographics, clinical characteristics, quality-of-life surveys, and treatment outcomes were recorded for patients with laryngeal symptoms associated with LCN compression at the brainstem. Results Forty-nine patients demonstrated LCN compression at the brainstem on imaging and presented with chief complaints of dysphonia (25 of 49, 51%), chronic cough (19 of 49, 39%), dysphoric breathing (3 of 49, 6%), and dysphagia (2 of 49, 4%). Poor initial scores were noted for Voice-Related Quality of Life (V-RQOL), Reflux Symptom Index, and Glottal Closure Index. Twenty-four patients underwent LCN decompression, of which 21 of 24 (88%) reported partial, near-complete, or complete improvement. Major perioperative complications occurred in four of 24 patients (17%). Patients who had undergone decompression were more likely to obtain complete/near-complete symptom resolution (10 of 24 patients, 42%) compared to those undergoing conservative treatments (2 of 25 patients, 8%) (P = 0.02). V-RQOL scores improved more in surgical patients [mean change score, 33.0 (standard deviation [SD], 31.2) than nonsurgical patients (mean change score 9.6, SD 20.9) (P = 0.03) (mean follow-up 3.0 years, SD 2.0). Conclusion Lower cranial nerve compression at the brainstem should be considered when all other etiologies are excluded. Retromastoid craniectomy with LCN decompression demonstrates an acceptable safety profile. Level of evidence 4 Laryngoscope, 129:2105-2111, 2019.

Understanding the real-world effect of pneumococcal conjugate vaccines (PCVs) on pneumonia mortality is crucial because of the expectation that increased PCV use will substantially reduce the burden of pneumonia deaths in children younger than 5 years. However, few post-vaccine introduction studies have estimated the benefits of PCV use on childhood mortality and results have been inconsistent. Therefore, we set out to assess the effect of introduction of ten-valent pneumococcal conjugate vaccine (PCV10) on pneumonia mortality in children in Brazil.In this retrospective observational study, we used publicly available mortality data of children aged 3-59 months in Brazil. We separated data by age group (3-11 months, 3-23 months, and 3-59 months) and stratified data by three different socioeconomic factors of Brazilian municipalities (in 2010): Human Development Index, proportion of children living in extreme poverty, and proportion of mothers with no primary education. We first examined long-term trends in childhood pneumonia mortality in Brazil (from 1980 to 2014). We then assessed the effect of PCV10-introduced in Brazil in 2010-both nationally and in municipalities stratified by socioeconomic status, with a synthetic control approach as our primary analytical method.Between 1980 and 2010, a period during which Brazil's Human Development Index rose substantially, national pneumonia mortality in children younger than 5 years decreased from about 150 to 15 deaths per 100 000 children younger than 5 years. Despite rapid uptake of PCV10 after its introduction in 2010, we observed a further vaccine-associated decline of about 10% in national childhood pneumonia mortality with our primary analytical method, with a high degree of uncertainty in the estimates. We observed larger reductions in municipal childhood pneumonia mortality in all three age groups (3-11 months, 3-23 months, and 3-59 months) in municipalities with a high percentage of extreme childhood poverty and mothers with no primary education, with the largest decrease observed in children aged 3-23 months in municipalities with low maternal education (24%, 95% credible interval 7-35).The large reduction observed from 1980 to 2010 in national pneumonia mortality in children younger than 5 years underscores that improvements in nutrition, hygiene, education, and health care have an important role in reducing pneumonia mortality. Although the PCV-associated reduction in childhood pneumonia mortality at the national level was modest, we found that PCV led to larger reductions in low-income municipalities. Similarly, large benefits might occur when PCVs are introduced in other low-income settings.BillMelinda Gates Foundation and National Institute of Allergy and Infectious Diseases.