Identification, mapping, and self-reported practice patterns of village doctors in Sitakunda subdistrict, Bangladesh.

Background: Informally trained health care providers, such as village doctors in Bangladesh, are crucial in providing health care services to the rural poor in low- and middle-income countries. Despite being one of the primary vendors of antibiotics in rural Bangladesh, village doctors often have limited knowledge about appropriate antibiotic use, leading to varied and potentially inappropriate dispensing and treatment practices. In this study, we aimed to identify, map, and survey village doctors in the Sitakunda subdistrict of Bangladesh to understand their distribution, practice characteristics, clinical behaviours, access to technologies, and use of these technologies for clinical decision-making. Methods: Using a 'snowball' sampling method, we identified and mapped 411 village doctors, with 371 agreeing to complete a structured survey. Results: The median distance between a residential household and the closest village doctor practice was 0.37 km, and over half of the practices (51.2%) were within 100 m of the major highway. Village doctors were predominately male (98.7%), with a median age of 39. After completing village doctor training, 39.4% had completed an internship, with a median of 15 years of practice experience. Village doctors reported seeing a median of 84 patients per week, including a median of five paediatric diarrhoea cases per week. They stocked a range of antibiotics, with ciprofloxacin and metronidazole being the most prescribed for diarrhoea. Most had access to phones with an internet connection and used online resources for clinical decision-making and guidance. Conclusions: The findings provide insights into the characteristics and practices of village doctors and point to the potential for internet and phone-based interventions to improve patient care and reduce inappropriate antibiotic use in this health care provider group.

Analysis of Cholera Risk in India: Insights from 2017-18 Serosurvey Data Integrated with Epidemiologic data and Societal Determinants from 2015-2019.

BACKGROUND: Indian subcontinent being an important region in the fight to eliminate cholera needs better cholera surveillance. Current methods miss most infections, skewing disease burden estimates. Triangulating serosurvey data, clinical cases, and risk factors could reveal India's true cholera risk. METHODS: We synthesized data from a nationally representative serosurvey, outbreak reports and risk factors like water, sanitation and the Multidimensional Poverty Index, to create a composite vulnerability index for assessing state-wise cholera risk in India. We tested 7,882 stored sera samples collected during 2017-18 from individuals aged 9-45 years, for vibriocidal antibodies to Vibrio cholerae O1 using a cut-off titre ≥320 defining as elevated titre. We also extracted data from the 2015-19 Integrated Disease Surveillance Programme and published cholera reports. RESULTS: Overall, 11.7% (CI: 10.4-13.3%) of the sampled population had an elevated titre of cholera vibriocidal antibodies (≥320). The Southern region experienced the highest incidence (16.8%, CI: 12.1-22.8), followed by the West (13.2%, CI: 10.0-17.3) and North (10.7%, CI: 9.3-12.3). Proportion of samples with an elevated vibriocidal titre (≥320) was significantly higher among individuals aged 18-45 years (13.0% CI: 11.2-15.1) compared to children 9-17 years (8.6%, CI 7.3-10.0, p<0.05); we found no differences between sex or urbanicity. Between 2015-2019, the Integrated Disease Surveillance Program (IDSP) reported 29,400 cases of cholera across the country. Using the composite vulnerability index, we found Karnataka, Madhya Pradesh, and West Bengal were the most vulnerable states in India in terms of risk of cholera. CONCLUSION: The present study showed that cholera infection is present in all five regions across India. The states with high cholera vulnerability could be prioritized for targeted prevention interventions.

Streptococcus pneumoniae carriage, serotypes, genotypes, and antimicrobial resistance trends among children in Portugal, after introduction of PCV13 in National Immunization Program: A cross-sectional study.

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018-2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009-2010 (pre-PCV13), 2011-2012 (early-PCV13), and 2015-2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4-6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1-5.6], and 2.9-fold, 95 %CI [1.3-6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance.

The yeast genus Tardiomyces gen. nov. with one new species and two new combinations.

PURPOSE: Rare yeasts species are increasingly reported as causative agents of invasive human infection. Proper identification and antifungal therapy are essential to manage these infections. Candida blankii is one of these emerging pathogens and is known for its reduced susceptibility to multiple antifungals. METHODS: To obtain more insight into the characteristics of this species, 26 isolates reported as C. blankii were investigated using genetic and phenotypical approaches. RESULTS: Among the 26 isolates, seven recovered either from blood, sputum, urine, or the oral cavity, displayed substantial genetic and some phenotypical differences compared to the other isolates, which were confirmed as C. blankii. We consider these seven strains to represent a novel species, Tardiomyces depauwii. Phylogenomics assigned C. blankii, C. digboiensis, and the novel species in a distinct branch within the order Dipodascales, for which the novel genus Tardiomyces is erected. The new combinations Tardiomyces blankii and Tardiomyces digboiensis are introduced. Differences with related, strictly environmental genera Sugiyamaella, Crinitomyces, and Diddensiella are enumerated. All three Tardiomyces species share the rare ability to grow up to 42 °C, display slower growth in nutrient-poor media, and show a reduced susceptibility to azoles and echinocandins. Characteristics of T. depauwii include high MIC values with voriconazole and a unique protein pattern. CONCLUSION: We propose the novel yeast species Tardiomyces depauwii and the transfer of C. blankii and C. digboiensis to the novel Tardiomyces genus.

Annual risk of hepatitis E virus infection and seroreversion: Insights from a serological cohort in Sitakunda, Bangladesh.

Hepatitis E virus (HEV) is a major cause of acute jaundice in South Asia. Gaps in our understanding of transmission are driven by non-specific symptoms and scarcity of diagnostics, impeding rational control strategies. In this context, serological data can provide important proxy measures of infection. We enrolled a population-representative serological cohort of 2,337 individuals in Sitakunda, Bangladesh. We estimated the annual risks of HEV infection and seroreversion both using serostatus changes between paired serum samples collected 9 months apart, and by fitting catalytic models to the age-stratified cross-sectional seroprevalence. At baseline, 15% (95 CI: 14-17%) of people were seropositive, with seroprevalence highest in the relatively urban south. During the study, 27 individuals seroreverted (annual seroreversion risk: 15%, 95 CI: 10-21%), and 38 seroconverted (annual infection risk: 3%, 95CI: 2-5%). Relying on cross-sectional seroprevalence data alone, and ignoring seroreversion, underestimated the annual infection risk five-fold (0.6%, 95 CrI: 0.5-0.6%). When we accounted for the observed seroreversion in a reversible catalytic model, infection risk was more consistent with measured seroincidence. Our results quantify HEV infection risk in Sitakunda and highlight the importance of accounting for seroreversion when estimating infection incidence from cross-sectional seroprevalence data.

State variation in neighborhood COVID-19 burden across the United States.

BACKGROUND: A lack of fine, spatially-resolute case data for the U.S. has prevented the examination of how COVID-19 infection burden has been distributed across neighborhoods, a key determinant of both risk and resilience. Without more spatially resolute data, efforts to identify and mitigate the long-term fallout from COVID-19 in vulnerable communities will remain difficult to quantify and intervene on. METHODS: We leveraged spatially-referenced data from 21 states collated through the COVID Neighborhood Project to examine the distribution of COVID-19 cases across neighborhoods and states in the U.S. We also linked the COVID-19 case data with data on the neighborhood social environment from the National Neighborhood Data Archive. We then estimated correlations between neighborhood COVID-19 burden and features of the neighborhood social environment. RESULTS: We find that the distribution of COVID-19 at the neighborhood-level varies within and between states. The median case count per neighborhood (coefficient of variation (CV)) in Wisconsin is 3078.52 (0.17) per 10,000 population, indicating a more homogenous distribution of COVID-19 burden, whereas in Vermont the median case count per neighborhood (CV) is 810.98 (0.84) per 10,000 population. We also find that correlations between features of the neighborhood social environment and burden vary in magnitude and direction by state. CONCLUSIONS: Our findings underscore the importance that local contexts may play when addressing the long-term social and economic fallout communities will face from COVID-19.

A lack of data on the geographic location of COVID-19 cases in the U.S has limited our ability to examine how COVID-19 burden has been distributed across neighborhoods within U.S. states. It may be that certain neighborhoods have borne a disproportionate burden of COVID-19 and are more likely to experience greater long-term social and economic consequences from the pandemic. We used data from 21 states to examine the distribution of COVID-19 cases across neighborhoods and states in the U.S. We find that the distribution of COVID-19 varies widely both within neighborhoods in a state, and between states. We also find that the features of the neighborhood social environment that are correlated with neighborhood COVID-19 burden vary by state. Our findings show that the local neighborhood may play an important role in addressing long-term social and economic consequences from COVID-19.

XBB.1.5 monovalent booster improves antibody binding and neutralization against emerging SARS-CoV-2 Omicron variants.

The rapid emergence of divergent SARS-CoV-2 variants has led to an update of the COVID-19 booster vaccine to a monovalent version containing the XBB.1.5 spike. To determine the neutralization breadth following booster immunization, we collected blood samples from 24 individuals pre- and post-XBB.1.5 mRNA booster vaccination (∼1 month). The XBB.1.5 booster improved both neutralizing activity against the ancestral SARS-CoV-2 strain (WA1) and the circulating Omicron variants, including EG.5.1, HK.3, HV.1, XBB.1.5 and JN.1. Relative to the pre-boost titers, the XBB.1.5 monovalent booster induced greater total IgG and IgG subclass binding, particular IgG4, to the XBB.1.5 spike as compared to the WA1 spike. We evaluated antigen-specific memory B cells (MBCs) using either spike or receptor binding domain (RBD) probes and found that the monovalent booster largely increases non-RBD cross-reactive MBCs. These data suggest that the XBB.1.5 monovalent booster induces cross-reactive antibodies that neutralize XBB.1.5 and related Omicron variants.

Severe COVID-19 in Vaccinated Adults With Hematologic Cancers in the Veterans Health Administration.

Importance: With SARS-CoV-2 transforming into an endemic disease and with antiviral treatments available, it is important to establish which patients remain at risk of severe COVID-19 despite vaccination. Objective: To quantify the associations of clinical and demographic variables with odds of severe COVID-19 among patients with hematologic cancers. Design, Setting, and Participants: This case-control study included all patients with hematologic malignant neoplasms in the national Veterans Health Administration (VHA) who had documented SARS-CoV-2 infection after vaccination. Groups of patients with severe (cases) vs nonsevere (controls) COVID-19 were compared. Data were collected between January 1, 2020, and April 5, 2023, with data on infection collected between January 1, 2021, and September 30, 2022. All patients with diagnostic codes for hematologic malignant neoplasms who had documented vaccination followed by documented SARS-CoV-2 infection and for whom disease severity could be assessed were included. Data were analyzed from July 28 to December 30, 2023. Exposures: Clinical (comorbidities, predominant viral variant, treatment for malignant neoplasm, booster vaccination, and antiviral treatment) and demographic (age and sex) variables shown in prior studies to be associated with higher or lower rates of severe COVID-19. Comorbidities included Alzheimer disease or dementia, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, heart failure, and peripheral vascular disease. Main Outcome and Measures: The main outcome was severe COVID-19 compared with nonsevere SARS-CoV-2 infection. Severe COVID-19 was defined as death within 28 days, mechanical ventilation, or hospitalization with use of dexamethasone or evidence of hypoxemia or use of supplemental oxygen. Multivariable logistic regression was used to estimate the associations of demographic and clinical variables with the odds of severe COVID-19, expressed as adjusted odds ratios (aORs) with 95% CIs. Results: Among 6122 patients (5844 [95.5%] male, mean [SD] age, 70.89 [11.57] years), 1301 (21.3%) had severe COVID-19. Age (aOR per 1-year increase, 1.05; 95% CI, 1.04-1.06), treatment with antineoplastic or immune-suppressive drugs (eg, in combination with glucocorticoids: aOR, 2.32; 95% CI, 1.93-2.80), and comorbidities (aOR per comorbidity, 1.35; 95% CI, 1.29-1.43) were associated with higher odds of severe disease, whereas booster vaccination was associated with lower odds (aOR, 0.73; 95% CI, 0.62-0.86). After oral antiviral drugs became widely used in March 2022, 20 of 538 patients (3.7%) with SARS-CoV-2 infection during this period had progression to severe COVID-19. Conclusions and Relevance: In this case-control study of patients with hematologic cancers, odds of severe COVID-19 remained high through mid-2022 despite vaccination, especially in patients requiring treatment.

Clinical surveillance systems obscure the true cholera infection burden in an endemic region.

Our understanding of cholera transmission and burden largely relies on clinic-based surveillance, which can obscure trends, bias burden estimates and limit the impact of targeted cholera-prevention measures. Serological surveillance provides a complementary approach to monitoring infections, although the link between serologically derived infections and medically attended disease incidence-shaped by immunological, behavioral and clinical factors-remains poorly understood. We unravel this cascade in a cholera-endemic Bangladeshi community by integrating clinic-based surveillance, healthcare-seeking and longitudinal serological data through statistical modeling. Combining the serological trajectories with a reconstructed incidence timeline of symptomatic cholera, we estimated an annual Vibrio cholerae O1 infection incidence rate of 535 per 1,000 population (95% credible interval 514-556), with incidence increasing by age group. Clinic-based surveillance alone underestimated the number of infections and reported cases were not consistently correlated with infection timing. Of the infections, 4 in 3,280 resulted in symptoms, only 1 of which was reported through the surveillance system. These results impart insights into cholera transmission dynamics and burden in the epicenter of the seventh cholera pandemic, where >50% of our study population had an annual V. cholerae O1 infection, and emphasize the potential for a biased view of disease burden and infection risk when depending solely on clinical surveillance data.

Underuse of Antiviral Drugs to Prevent Progression to Severe COVID-19 - Veterans Health Administration, March-September 2022.

Antiviral drugs reduce the rate of progression to severe COVID-19 when given to patients with mild-to-moderate disease within 5 days of symptom onset. Despite being recommended for patients at high risk for progression to severe COVID-19 because of age or chronic conditions, reported antiviral use among the general adult population has been ≤35%. To ascertain reasons for underuse of antiviral medications to prevent severe COVID-19 and propose interventions accordingly, a detailed review was conducted of 110 Veterans Health Administration patients with mild-to-moderate infection at high risk for progression because of underlying conditions (organ transplantation or hematologic malignancies) who did not receive an antiviral drug. Among these 110 patients, all of whom had received COVID-19 vaccine, 22 (20.0%) were offered treatment but declined, and 88 (80.0%) were not offered treatment. Among the 88 patients not offered treatment, provider reasons included symptom duration of >5 days (22.7%), concern about possible drug interactions (5.7%), or absence of symptoms (22.7%); however, among nearly one half (43 of 88; 48.9%) of these patients, no reason other than mild symptoms was given. Among 24 (55.8%) of those 43 patients, follow-up was limited to telephone calls to report test results and inquire about symptom evolution, with no documentation of treatment being offered. These findings suggest that education of patients, providers, and medical personnel tasked with follow-up calls, combined with advance planning in the event of a positive test result, might improve the rate of recommended antiviral medication use to prevent severe COVID-19-associated illness, including death.

Risk of severe coronavirus disease 2019 despite vaccination in patients requiring treatment with immune-suppressive drugs: A nationwide cohort study of US Veterans.

BACKGROUND: Patients taking immune-suppressive drugs are at increased risk of severe coronavirus disease 2019 (COVID-19), not fully ameliorated by vaccination. We assessed the contributions of clinical and demographic factors to the risk of severe disease despite vaccination in patients taking immune-suppressive medications for solid organ transplantation (SOT), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis. METHODS: Veterans Health Administration electronic health records were used to identify patients diagnosed with RA, IBD, psoriasis, or SOT who had been vaccinated against severe acute respiratory syndrome coronavirus 2, were subsequently infected, and had received immune-suppressive drugs within 3 months before infection. The association of severe (defined as hypoxemia, mechanical ventilation, dexamethasone use, or death) versus non-severe COVID-19 with the use of immune-suppressive and antiviral drugs and clinical covariates was assessed by multivariable logistic regression. RESULTS: Severe COVID-19 was more common in patients with SOT (230/1011, 22.7%) than RA (173/1355, 12.8%), IBD (51/742, 6.9%), or psoriasis (82/1125, 7.3%). Age was strongly associated with severe COVID-19, adjusted odds ratio (aOR) of 1.04 (CI 1.03-1.05) per year. Comorbidities indicating chronic brain, heart, lung, or kidney damage were also associated with severity, aOR 1.35-2.38. The use of glucocorticoids was associated with increased risk (aOR 1.66, CI 1.39-2.18). Treatment with antivirals was associated with reduced severity, for example, aOR 0.28 (CI 0.13-0.62) for nirmatrelvir/ritonavir. CONCLUSION: The risk of severe COVID-19 despite vaccination is substantial in patients taking immune-suppressive drugs, more so in patients with SOT than in patients with inflammatory diseases. Age and severe comorbidities contribute to risk, as in the general population. Oral antivirals were very beneficial but not widely used.

Potential for Person-to-Person Transmission of Henipaviruses: A Systematic Review of the Literature.

Nipah virus Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route. The risk posed by related henipaviruses, including Hendra virus (HeV) and Nipah virus Malaysia (NiVM), is less clear. We conducted a broad search of the literature encompassing both human infections and animal models to synthesize evidence about potential for person-to-person spread. More than 600 human infections have been reported in the literature, but information on viral shedding was only available for 40 case-patients. There is substantial evidence demonstrating person-to-person transmission of NiVB, and some evidence for NiVM. Less direct evidence is available about the risk for person-to-person transmission of HeV, but animals infected with HeV shed more virus in the respiratory tract than those infected with NiVM, suggesting potential for transmission. As the group of known henipaviruses continues to grow, shared protocols for conducting and reporting from human investigations and animal experiments are urgently needed.

Maximizing Readmission Reduction in Colon Cancer Patients.

INTRODUCTION: Multiple studies have identified risk factors for readmission in colon cancer patients. We need to determine which risk factors, when modified, produce the greatest decrease in readmission for patients so that limited resources can be used most effectively by implementing targeted evidence-based performance improvements. We determined the potential impact of various modifiable risk factors on reducing 30-d readmission in colon cancer patients. METHODS: We used a cohort design with the 2012-2020 American College of Surgeons' National Surgical Quality Improvement Program data to track colon cancer patients for 30 d following surgery. Colon cancer patients who received colectomies and were discharged alive were included. Readmission (to the same or another hospital) for any reason within 30 d of the resection was the outcome measure. Modifiable risk factors were the use of minimally invasive surgery (MIS) versus open colectomy, mechanical bowel preparation, preoperative antibiotic use, functional status, smoking, complications (deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, infections, anastomotic leakage, prolonged postoperative ileus, extensive blood loss, and sepsis), serum albumin, and hematocrit. RESULTS: 111,691 patients with colon cancer were included in the analysis. About half of the patients were male, most were aged 75 or older, and were discharged home. Overall, 11,138 patients (10.0%) were readmitted within 30 d of surgery. In adjusted analysis, the reduction in readmission would be largest by preventing both prolonged ileus and by switching open colectomies to MIS (28.0% relative reduction) followed by preventing anastomotic leaks (6.2% relative reduction). Improving other modifiable risk factors would have a more limited impact. CONCLUSIONS: The focus of readmission reduction should be on preventing prolonged ileus, increasing the use of MIS, and preventing anastomotic leaks.

The upper respiratory tract microbiota of healthy adults is affected by Streptococcus pneumoniae carriage, smoking habits, and contact with children.

BACKGROUND: The microbiota of the upper respiratory tract is increasingly recognized as a gatekeeper of respiratory health. Despite this, the microbiota of healthy adults remains understudied. To address this gap, we investigated the composition of the nasopharyngeal and oropharyngeal microbiota of healthy adults, focusing on the effect of Streptococcus pneumoniae carriage, smoking habits, and contact with children. RESULTS: Differential abundance analysis indicated that the microbiota of the oropharynx was significantly different from that of the nasopharynx (P < 0.001) and highly discriminated by a balance between the classes Negativicutes and Bacilli (AUC of 0.979). Moreover, the oropharynx was associated with a more homogeneous microbiota across individuals, with just two vs. five clusters identified in the nasopharynx. We observed a shift in the nasopharyngeal microbiota of carriers vs. noncarriers with an increased relative abundance of Streptococcus, which summed up to 30% vs. 10% in noncarriers and was not mirrored in the oropharynx. The oropharyngeal microbiota of smokers had a lower diversity than the microbiota of nonsmokers, while no differences were observed in the nasopharyngeal microbiota. In particular, the microbiota of smokers, compared with nonsmokers, was enriched (on average 16-fold) in potential pathogenic taxa involved in periodontal diseases of the genera Bacillus and Burkholderia previously identified in metagenomic studies of cigarettes. The microbiota of adults with contact with children resembled the microbiota of children. Specifically, the nasopharyngeal microbiota of these adults had, on average, an eightfold increase in relative abundance in Streptococcus sp., Moraxella catarrhalis, and Haemophilus influenzae, pathobionts known to colonize the children's upper respiratory tract, and a fourfold decrease in Staphylococcus aureus and Staphylococcus lugdunensis. CONCLUSIONS: Our study showed that, in adults, the presence of S. pneumoniae in the nasopharynx is associated with a shift in the microbiota and dominance of the Streptococcus genus. Furthermore, we observed that smoking habits are associated with an increase in bacterial genera commonly linked to periodontal diseases. Interestingly, our research also revealed that adults who have regular contact with children have a microbiota enriched in pathobionts frequently carried by children. These findings collectively contribute to a deeper understanding of how various factors influence the upper respiratory tract microbiota in adults. Video Abstract.

Virtual Reality for Preoperative Planning in Complex Surgical Oncology: A Single-Center Experience.

INTRODUCTION: Virtual reality models (VRM) are three-dimensional (3D) simulations of two-dimensional (2D) images, creating a more accurate mental representation of patient-specific anatomy. METHODS: Patients were retrospectively identified who underwent complex oncologic resections whose operations differed from preoperative plans between April 2018 and April 2019. Virtual reality modeling was performed based on preoperative 2D images to assess feasibility of use of this technology to create models. Preoperative plans made based upon 2D imaging versus VRM were compared to the final operations performed. Once the use of VRM to create preoperative plans was deemed feasible, individuals undergoing complex oncologic resections whose operative plans were difficult to define preoperatively were enrolled prospectively from July 2019 to December 2021. Preoperative plans made based upon 2D imaging and VRM by both the operating surgeon and a consulting surgeon were compared to the operation performed. Confidence in each operative plan was also measured. RESULTS: Twenty patients were identified, seven retrospective and 13 prospective, with tumors of the liver, pancreas, retroperitoneum, stomach, and soft tissue. Retrospectively, VRM were unable to be created in one patient due to a poor quality 2D image; the remainder (86%) were successfully able to be created and examined. Virtual reality modeling more clearly defined the extent of resection in 50% of successful cases. Prospectively, all VRM were successfully performed. The concordance of the operative plan with VRM was higher than with 2D imaging (92% versus 54% for the operating surgeon and 69% versus 23% for the consulting surgeon). Confidence in the operative plan after VRM compared to 2D imaging also increased for both surgeons (by 15% and 8% for the operating and consulting surgeons, respectively). CONCLUSIONS: Virtual reality modeling is feasible and may improve preoperative planning compared to 2D imaging. Further investigation is warranted.

Water, Sanitation, and Cholera in Sub-Saharan Africa.

Improvements in water and sanitation should reduce cholera risk though the associations between cholera and specific water and sanitation access measures remain unclear. We estimated the association between eight water and sanitation measures and annual cholera incidence access across sub-Saharan Africa (2010-2016) for data aggregated at the country and district levels. We fit random forest regression and classification models to understand how well these measures combined might be able to predict cholera incidence rates and identify high cholera incidence areas. Across spatial scales, piped or "other improved" water access was inversely associated with cholera incidence. Access to piped water, septic or sewer sanitation, and septic, sewer, or "other improved" sanitation were associated with decreased district-level cholera incidence. The classification model had moderate performance in identifying high cholera incidence areas (cross-validated-AUC 0.81, 95% CI 0.78-0.83) with high negative predictive values (93-100%) indicating the utility of water and sanitation measures for screening out areas that are unlikely to be at high cholera risk. While comprehensive cholera risk assessments must incorporate other data sources (e.g., historical incidence), our results suggest that water and sanitation measures could alone be useful in narrowing the geographic focus for detailed risk assessments.

Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome.

Fatty acid isomers are responsible for an under-reported lipidome diversity across all kingdoms of life. Isomers of unsaturated fatty acids are often masked in contemporary analysis by incomplete separation and the absence of sufficiently diagnostic methods for structure elucidation. Here, we introduce a comprehensive workflow, to discover unsaturated fatty acids through coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds. The workflow encompasses semi-automated data analysis and enables de novo identification in complex media including human plasma, cancer cell lines and vernix caseosa. The targeted analysis including ozonolysis enables structural assignment over a dynamic range of five orders of magnitude, even in instances of incomplete chromatographic separation. Thereby we expand the number of identified plasma fatty acids two-fold, including non-methylene-interrupted fatty acids. Detection, without prior knowledge, allows discovery of non-canonical double bond positions. Changes in relative isomer abundances reflect underlying perturbations in lipid metabolism.