Following a four-year annual praziquantel treatment campaign the resulting prevalence of S. mansoni was seen to differ among individual villages along the Kenyan shore of Lake Victoria. We have investigated possible inherent differences in snail-related aspects of transmission among such 10 villages, including six persistent hotspot (PHS) villages (≤30% reduction in prevalence following repeated treatments) located along the west-facing shore of the lake, and four PZQ-responding (RESP) villages (>30% prevalence reduction following repeated treatment) along Winam Gulf. When taking into account all sampling sites and times and water hyacinth presence/absence, shoreline-associated B. sudanica from PHS and RESP villages did not differ in relative abundance or prevalence of S. mansoni infection. Water hyacinth intrusions were associated with increased B. sudanica abundance. The deeper water snail Biomphalaria choanomphala was significantly more abundant in the PHS villages and prevalence of S. mansoni among villages both before and after control was positively correlated with B. choanomphala abundance. Worm recoveries from sentinel mice did not differ between PHS and RESP villages, and abundance of non-schistosome trematode species was not associated with S. mansoni abundance. Biomphalaria choanomphala provides an alternative, deepwater mode of transmission that may favor greater persistence of S. mansoni in PHS villages. As we found evidence for ongoing S. mansoni transmission in all 10 villages, we conclude conditions conducive for transmission and reinfection occur ubiquitously. This argues for an integrated, basin-wide plan for schistosomiasis control to counteract rapid reinfections facilitated by large snail populations and movements of infected people around the lake.

The global shipping network (GSN) has been suggested as a pathway for the establishment and reintroduction of Aedes aegypti and Aedes albopictus primarily via the tire trade. We used historical maritime movement data in combination with an agent-based model to understand invasion risk in the United States Gulf Coast and how the risk of these invasions could be reduced. We found a strong correlation between the total number of cargo ship arrivals at each port and likelihood of arrival by both Ae. aegypti and Ae. albopictus. Additionally, in 2012, 99.2% of the arrivals into target ports had most recently visited ports occupied by both Ae. aegypti and Ae. albopictus, increasing risk of Aedes invasion. Model results indicated that detection and removal of mosquitoes from containers when they are unloaded at a port may be more effective in reducing the establishment of mosquito populations compared to eradication efforts that occur while onboard the vessel, suggesting detection efforts should be focused on unloaded containers. To reduce the risk of invasion and reintroduction of Ae. aegypti and Ae. albopictus, surveillance and control efforts should be employed when containers leave high risk locations and when they arrive in ports at high risk of establishment. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

BACKGROUND: Community randomised trials have had mixed success in implementing combination prevention strategies that diagnose 90% of people living with HIV, initiate and retain on antiretroviral therapy (ART) 90% of those diagnosed, and achieve viral load suppression in 90% of those on ART (90-90-90). The Bukoba Combination Prevention Evaluation (BCPE) aimed to achieve 90-90-90 in Bukoba Municipal Council, Tanzania, by scaling up new HIV testing, linkage, and retention interventions. METHOD: We did population-based, cross-sectional surveys before and after our community-wide intervention in Bukoba-a mixed urban and rural council of approximately 150 000 residents located on the western shore of Lake Victoria in Tanzania. BCPE interventions were implemented in 11 government-supported health-care facilities throughout Bukoba from Oct 1, 2014, to March 31, 2017, when national ART-eligibility guidelines expanded from CD4 counts of less than 350 cells per μL (Oct 1, 2014-Dec 31, 2015) and 500 or less cells per μL (Jan 1, 2016-Sept 30, 2016) to any CD4 cell count (test and treat, Oct 1, 2016-March 31, 2017). We used pre-intervention (Nov 4, 2013-Jan 25, 2014) and post-intervention (June 21, 2017-Sept 20, 2017) population-based household surveys to assess population prevalence of undiagnosed HIV infection and ART coverage, and progress towards 90-90-90, among residents aged 18-49 years. FINDINGS: During the 2·5-year intervention, BCPE did 133 695 HIV tests, diagnosed and linked 3918 people living with HIV to HIV care at 11 Bukoba facilities, and returned to HIV care 604 patients who had stopped care. 4795 and 5067 residents aged 18-49 years participated in pre-intervention and post-intervention surveys. HIV prevalence before and after the intervention was similar: pre-intervention 8·9% (95% CI 7·5-10·4); post-intervention 8·4% (6·9-9·9). Prevalence of undiagnosed HIV infection decreased from 4·7% to 2·0% (prevalence ratio 0·42, 95% CI 0·31-0·57), and current ART use among all people living with HIV increased from 32·2% to 70·9% (2·20, 1·82-2·66) overall, 23·0% to 62·1% among men (2·70, 1·84-3·96), and 16·7% to 64·4% among people aged 18-29 years (3·87, 2·54-5·89). Of 436 and 435 people living with HIV aged 18-49 years who participated in pre-intervention and post-intervention surveys, previous HIV diagnosis increased from 47·4% (41·3-53·4) to 76·2% (71·8-80·6), ART use among diagnosed people living with HIV increased from 68·0% (60·9-75·2) to 93·1% (90·2-96·0), and viral load suppression of those on ART increased from 88·7% (83·6-93·8) to 91·3% (88·6-94·1). INTERPRETATION: BCPE findings suggest scaling up recommended HIV testing, linkage, and retention interventions can help reduce prevalence of undiagnosed HIV infection, increase ART use among all people living with HIV, and make substantial progress towards achieving 90-90-90 in a relatively short period. BCPE facility-based testing and linkage interventions are undergoing national scale up to help achieve 90-90-90 in Tanzania. FUNDING: US Presidents' Emergency Plan for AIDS Relief.

US gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for Ng identification, capacity for culturing Ng in the US has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet, AST is critical for detecting and monitoring AR-Ng. In 2016, CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up national capacity for detecting several resistance threats including Ng. AR-Ng testing, a sub-activity of CDC's AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in MD, TN, TX, WA), and CDC's national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 Ng isolates, and CDC received 531 and 646 concerning isolates, and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported laboratory capacity for Ng-AST and associated genetic marker detection, expanding pre-existing notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.

Reducing HIV-related morbidity and mortality, and effectively eliminating HIV transmission risk, depends on use of antiretroviral therapy (ART) to achieve and maintain viral load suppression (VLS)* (1,2). By 2020, sub-Saharan African countries are working to achieve VLS among 90% of persons using ART and 73% of all persons living with HIV infection (1). In Tanzania, a country with 1.4 million persons with HIV infection, 49.6% of HIV-positive persons aged 15-49 years had achieved VLS in 2017, including only 21.5% of men and 44.6% of women aged 25-29 years (3). To identify interventions that might increase VLS in Tanzania, and reduce VLS-associated sex and age-group disparities, the Bukoba Combination Prevention Evaluation (BCPE) scaled up new HIV testing, linkage to care, and retention on ART interventions throughout Bukoba Municipal Council (Bukoba), Tanzania, during October 2014-March 2017 (4,5). Located on the western shore of Lake Victoria, Bukoba is a mixed urban and rural municipality of 150,000 persons and capital of Kagera Region. Of the 31 regions of Tanzania, Kagera has the fourth highest prevalence of HIV infection (6.8%) among residents aged 15-49 years (3). CDC analyzed data from BCPE preintervention and postintervention surveys and found that VLS prevalence among HIV-positive Bukoba residents aged 18-49 years increased approximately twofold overall (from 28.6% to 64.8%) and among women (33.3% to 67.8%) and approximately threefold among men (20.5% to 59.1%) and young adults aged 18-29 years (15.6% to 56.7%). During 2017, BCPE facility-based testing and linkage interventions were approved as new service delivery models by the Tanzania Ministry of Health, Community Development, Gender, Elderly and Children (4,5). After a successful rollout to 208 facilities in 11 regions in 2018, BCPE interventions are being scaled up in all regions of Tanzania in 2019 with support from the United States President's Emergency Plan for AIDS Relief (PEPFAR).

Following a 4-year annual praziquantel (PZQ) treatment campaign, the resulting prevalence of Schistosoma mansoni was seen to differ among individual villages along the Kenyan shore of Lake Victoria. We have investigated possible inherent differences in snail-related aspects of transmission among such 10 villages, including six persistent hotspot (PHS) villages (</= 30% reduction in prevalence following repeated treatments) located along the west-facing shore of the lake and four PZQ-responding (RESP) villages (> 30% prevalence reduction following repeated treatment) along the Winam Gulf. When taking into account all sampling sites, times, and water hyacinth presence/absence, shoreline-associated Biomphalaria sudanica from PHS and RESP villages did not differ in relative abundance or prevalence of S. mansoni infection. Water hyacinth intrusions were associated with increased B. sudanica abundance. The deeper water snail Biomphalaria choanomphala was significantly more abundant in the PHS villages, and prevalence of S. mansoni among villages both before and after control was positively correlated with B. choanomphala abundance. Worm recoveries from sentinel mice did not differ between PHS and RESP villages, and abundance of non-schistosome trematode species was not associated with S. mansoni abundance. Biomphalaria choanomphala provides an alternative, deepwater mode of transmission that may favor greater persistence of S. mansoni in PHS villages. As we found evidence for ongoing S. mansoni transmission in all 10 villages, we conclude that conditions conducive for transmission and reinfection occur ubiquitously. This argues for an integrated, basin-wide plan for schistosomiasis control to counteract rapid reinfections facilitated by large snail populations and movements of infected people around the lake.

Globalization has opened many fronts for disease outbreaks because of the quick movement of people and porous borders around the world. The emergence of zoonotic diseases and other communicable diseases highlights the need for implementation of the Global Health Security Agenda packages if countries are to achieve compliance with International Health Regulations (IHR 2005). Health workforce development is one of the critical components that must be addressed with utmost urgency if gaps in early disease detection and response are to be addressed. In this regard, this case study is based on a measles outbreak investigation in Uganda simulating a real-life outbreak investigation by field epidemiologists and seeks to demonstrate the principles of applied epidemiology outlining the critical steps in outbreak investigations and generation of evidence for decision making. It aims to shore up the health workforce capacity by providing practical training for field epidemiology students and professionals that builds their skills in outbreak investigation. This case study can be completed in less than three hours.

Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the mAbs bound HAs from multiple strains of group 1 viruses, and one mAb, 05-2G02, bound to both group 1 and group 2 influenza A HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two mAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One mAb, 70-1F02, was co-crystallized with H5 HA and showed similar heavy chain only interactions as a the previously described anti-stalk antibody CR6261. Finally, we showed that antibodies that compete with these mAbs are prevalent in serum from an individual recently infected with A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections with zoonotic or emerging pandemic influenza viruses.IMPORTANCE The rise in zoonotic infections of humans with emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually worldwide. Currently available anti-viral treatment options include only neuraminidase inhibitors, but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. Alternative therapeutics are urgently needed. Broadly protective antibodies that target the conserved 'stalk' domain of the hemagglutinin represent potential potent antiviral prophylactic and therapeutic agents that can assist pandemic preparedness. Here, we describe four human monoclonal antibodies that target conserved regions of influenza HA and characterize their binding spectrum, as well as their protective capacity in prophylactic and therapeutic settings against a lethal challenge with a zoonotic influenza virus.

Occupational fatality surveillance has identified that fishing vessel disasters, such as sinkings and capsizings, continue to contribute to the most deaths among crewmembers in the US fishing industry. When a fishing vessel sinks at sea, crewmembers are at risk of immersion in water and subsequent drowning. This study examined survival factors for crewmembers following cold water immersion after the sinking of decked commercial fishing vessels in Alaskan waters during 2000-2014. Two immersion scenarios were considered separately: immersion for any length of time, and long-term immersion defined as immersion lasting over 30 min. Logistic regression was used to predict the odds of crewmember survival. Of the 617 crewmembers onboard 187 fishing vessels that sank in Alaska during 2000-2014, 557 (90.3%) survived and 60 died. For crewmembers immersed for any length of time, the significant adjusted predictors of survival were: entering a life-raft, sinking within three miles of shore, the sinking not being weather-related, and working as a deckhand. For crewmembers immersed for over 30 min, the significant adjusted predictors of survival were: wearing an immersion suit, entering a life-raft, working as a deckhand, and the sinking not being weather-related. The results of this analysis demonstrate that in situations where cold water immersion becomes inevitable, having access to well-maintained, serviceable lifesaving equipment and the knowledge and skills to use it properly are critical.

Personal protective equipment (PPE) that protects healthcare workers from infection is a critical component of infection control strategies in healthcare settings. During a public health emergency response, protecting healthcare workers from infectious disease is essential, given that they provide clinical care to those who fall ill, have a high risk of exposure, and need to be assured of occupational safety. Like most goods in the United States, the PPE market supply is based on demand. The US PPE supply chain has minimal ability to rapidly surge production, resulting in challenges to meeting large unexpected increases in demand that might occur during a public health emergency. Additionally, a significant proportion of the supply chain is produced off-shore and might not be available to the US market during an emergency because of export restrictions or nationalization of manufacturing facilities. Efforts to increase supplies during previous public health emergencies have been challenging. During the 2009 H1N1 influenza pandemic and the 2014 Ebola virus epidemic, the commercial supply chain of pharmaceutical and healthcare products quickly became critical response components. This article reviews lessons learned from these responses from a PPE supply chain and systems perspective and examines ways to improve PPE readiness for future responses.

Importance: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. Objective: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. Evidence Review: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. Findings: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. Conclusion and Relevance: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

OBJECTIVE: This field study aimed to assess the noise reduction of hearing protection for individual workers, demonstrate the effectiveness of training on the level of protection achieved, and measure the time required to implement hearing protector fit testing in the workplace. DESIGN: The National Institute for Occupational Safety and Health (NIOSH) conducted field studies in Louisiana and Texas to test the performance of HPD Well-Fit. STUDY SAMPLE: Fit tests were performed on 126 inspectors and engineers working in the offshore oil industry. RESULTS: Workers were fit tested with the goal of achieving a 25-dB PAR. Less than half of the workers were achieving sufficient protection from their hearing protectors prior to NIOSH intervention and training; following re-fitting and re-training, over 85% of the workers achieved sufficient protection. Typical test times were 6-12 minutes. CONCLUSIONS: Fit testing of the workers' earplugs identified those workers who were and were not achieving the desired level of protection. Recommendations for other hearing protection solutions were made for workers who could not achieve the target PAR. The study demonstrates the need for individual hearing protector fit testing and addresses some of the barriers to implementation.

Campylobacter lari is frequently isolated from shore birds and can cause illness in humans. Here, we report the draft whole-genome sequence of a urease-positive strain of C. lari that was isolated in estuarial water on the coast of Delaware, USA.

Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.

In August 2014, PulseNet, the national molecular subtyping network for foodborne disease surveillance, detected a multistate cluster of Salmonella enterica serotype Newport infections with an indistinguishable pulse-field gel electrophoresis (PFGE) pattern (XbaI PFGE pattern JJPX01.0061). Outbreaks of illnesses associated with this PFGE pattern have previously been linked to consumption of tomatoes harvested from Virginia's Eastern Shore in the Delmarva region and have not been linked to cucumbers or other produce items. To identify the contaminated food and find the source of the contamination, CDC, state and local health and agriculture departments and laboratories, and the Food and Drug Administration (FDA) conducted epidemiologic, traceback, and laboratory investigations. A total of 275 patients in 29 states and the District of Columbia were identified, with illness onsets occurring during May 20-September 30, 2014. Whole genome sequencing (WGS), a highly discriminating subtyping method, was used to further characterize PFGE pattern JJPX01.0061 isolates. Epidemiologic, microbiologic, and product traceback evidence suggests that cucumbers were a source of Salmonella Newport infections in this outbreak. The epidemiologic link to a novel outbreak vehicle suggests an environmental reservoir for Salmonella in the Delmarva region that should be identified and mitigated to prevent future outbreaks.

A(H1N1)pdm09 influenza A viruses predominated in the 2013-2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses.

The non-covalent interactions that mediate trimerization of the influenza hemagglutinin (HA) are important determinants of its biological activities. Recent studies have demonstrated that mutations in the HA trimer interface affect the thermal and pH sensitivities of HA, suggesting a possible impact on vaccine stability (Farnsworth et al. 2011. Vaccine 29:: 1529-1533). We used size exclusion chromatography analysis of recombinant HA ectodomain to compare the differences among recombinant trimeric HA proteins from early 2009 pandemic H1N1 viruses, which dissociate to monomers, with those of more recent virus HAs that can be expressed as trimers. We analyzed differences amongst the HA sequences and identified inter-molecular interactions mediated by the residue at position 374 (HA0 numbering) of the HA2 sub-domain as critical for HA trimer stability. Crystallographic analyses of HA from the recent H1N1 virus A/Washington/5/2011 highlight the structural basis for this observed phenotype. It remains to be seen whether more recent viruses with this mutation will yield more stable vaccines in the future. IMPORTANCE: Hemagglutinins from the early 2009 H1N1 pandemic viruses are unable to maintain a trimeric complex when expressed in a recombinant system. However HAs from 2010 and 2011 strains are more stable and our work highlights the improvement in stability can be attributed to an E47K substitution in the HA2 subunit of the stalk that emerged naturally in the circulating viruses.

Recent advances in instrumentation and data analysis in field flow fractionation and multi-angle light scattering (FFF-MALS) have enabled greater use of this technique to characterize and quantitate viruses. In this study, the FFF-MALS technique was applied to the characterization and quantitation of type A influenza virus particles to assess its usefulness for vaccine preparation. The use of FFF-MALS for quantitation and measurement of control particles provided data accurate to within 5% of known values, reproducible with a coefficient of variation of 1.9%. The methods, sensitivity and limit of detection were established by analyzing different volumes of purified virus, which produced a linear regression with fitting value R2 of 0.99. FFF-MALS was further applied to detect and quantitate influenza virus in the supernatant of infected MDCK cells and allantoic fluids of infected eggs. FFF fractograms of the virus present in these different fluids revealed similar distribution of monomeric and oligomeric virions. However, the monomer fraction of cell grown virus has greater size variety. Notably, beta-propialactone (BPL) inactivation of influenza viruses did not influence any of the FFF-MALS measurements. Quantitation analysis by FFF-MALS was compared to infectivity assays and real-time RT-PCR (qRT-PCR) and the limitations of each assay were discussed.

Organisms, including Vibrio cholerae, can be transferred between harbors in the ballast water of ships. Zones in the Caribbean region where distance from shore and water depth meet International Maritime Organization guidelines for ballast water exchange are extremely limited. Use of ballast water treatment systems could mitigate the risk for organism transfer.

Native and non-native ligands of the T cell receptor (TCR), including antibodies, have been proposed to induce signaling in T cells via intra- or intersubunit conformational rearrangements within the extracellular regions of TCR complexes. We have investigated whether any signatures can be found for such postulated structural changes during TCR triggering induced by antibodies, using crystallographic and mutagenesis-based approaches. The crystal structure of murine CD3epsilon complexed with the mitogenic anti-CD3epsilon antibody 2C11 enabled the first direct structural comparisons of antibody-liganded and unliganded forms of CD3epsilon from a single species, which revealed that antibody binding does not induce any substantial rearrangements within CD3epsilon. Saturation mutagenesis of surface-exposed CD3epsilon residues, coupled with assays of antibody-induced signaling by the mutated complexes, suggests a new configuration for the complex within which CD3epsilon is highly exposed and reveals that no large new CD3epsilon interfaces are required to form during antibody-induced signaling. The TCR complex therefore appears to be a structure that is capable of initiating intracellular signaling in T cells without substantial structural rearrangements within or between the component subunits. Our findings raise the possibility that signaling by native ligands might also be initiated in the absence of large structural rearrangements in the receptor.

Abraham Flexner's 1910 report is credited with promoting critical reforms in medical education. Because Flexner advocated scientific rigor and standardization in medical education, his report has been perceived to place little emphasis on the importance of public health in clinical education and training. However, a review of the report reveals that Flexner presciently identified at least three public-health-oriented principles that contributed to his arguments for medical education reform: (1) The training, quality, and quantity of physicians should meet the health needs of the public, (2) physicians have societal obligations to prevent disease and promote health, and medical training should include the breadth of knowledge necessary to meet these obligations, and (3) collaborations between the academic medicine and public health communities result in benefits to both parties. In this article, commemorating the Flexner Centenary, the authors review the progress of U.S. and Canadian medical schools in addressing these principles in the context of contemporary societal health needs, provide an update on recent efforts to address what has long been perceived as a deficit in medical education (inadequate grounding of medical students in public health), and provide new recommendations on how to create important linkages between medical education and public health. Contemporary health challenges that require a public health approach in addition to one-on-one clinical skills include containing epidemics of preventable chronic diseases, reforming the health care system to provide equitable high-quality care to populations, and responding to potential disasters in an increasingly interconnected world. The quantitative skills and contextual knowledge that will prepare physicians to address these and other population health problems constitute the basics of public health and should be included throughout the continuum of medical education.