Writing Support Group for Medical School Faculty-A Simple Way to Do It.

Problem: Writing for publication is a core activity for many medical school faculty, but faculty report numerous challenges to publication. To help address these challenges, some medical schools establish writing support programs, but those programs are often resource-intensive, involving didactic courses, accountability groups, formal mentorships, and even assistance from professional writers. Not all medical schools, however, provide resources for such programs, and many faculty members, especially clinicians, lack time needed to participate. Furthermore, success of these programs is typically judged by the total number of papers published. However, many clinicians would judge success as publication of the occasional papers they decide to write, not the total number of papers they or the group publish. With these issues in mind, we established a low-resource writing program focused on individual acceptance rates rather than total publications. Intervention: Our writing program is an informal group that meets monthly. Members bring their ideas for papers and drafts of papers, and other members provide critique and suggestions for improvement. Members then revise their papers to address that critique prior to journal submission. There are no formal or assigned mentors, courses, lectures, or writing assistants. Context: The program takes place in our family medicine department, in which faculty have various roles. Some group members are clinician-educators seeking to publish occasional clinical reviews or research articles; others are PhDs seeking to publish on aspects of their work. Impact: During the six years of the program, 86% of papers reviewed by the group were accepted for publication and 94% of those were accepted by the journal to which they were first submitted. Publication success rate of individual members averaged 79%. This exceeds the 30-40% acceptance rate for scholarly journals worldwide. Group members published an average of 5.2 papers per member, with some publishing as few as 2-3 papers and others as many as 10-11. Lessons Learned: An informal, low-resource writing program in medical school departments can help faculty reach their publication goals. We found that members were satisfied by having the group help them publish whatever number of papers they decided to write. The program's simple, informal approach fostered a culture of respectful and collegial interactions, in which members learned to depend on and accept critiques from colleagues. Finally, an unexpected benefit of our program resulted from membership of both clinicians and non-clinicians. This provided feedback from individuals with different perspectives, which enhanced development of manuscripts.

Competency Status and Desire for Training in Core Public Health Domains: An Analysis by Job Level.

CONTEXT: Although trainings on core public health domains are widely available, and experts concur that competency in multiple core domains (analysis/assessment, leadership, communication, etc) is desirable for public health professionals, many still lack such competency. Employee job level could be a factor, as organizational research indicates that broad skill sets often hold importance mainly for higher-level employees. OBJECTIVE: This study examines whether the association between competency and desire for training in core public health domains depends on job level. DESIGN: A training preferences and domain competency survey of public health professionals: nonmanagers (n = 790), middle managers (n = 332), and upper managers (n = 69). The association of competency in domains overall with number of related training topics desired was examined using median tests. The association of competency in individual domains with desire for specific related training topics was assessed using logistic regressions adjusted for education. SETTINGS: Public health departments in the US Southwest (2013-2019). MAIN OUTCOME MEASURES: Competence in core domains: Financial Planning and Management, Analysis/Assessment, Communication, Cultural Competency, Leadership/Systems Thinking, Policy Development/Program Planning, Public Health Sciences, and Community Dimensions of Practice. Desire for training (yes/no) in 25 domain-related topics. RESULTS: Upper managers lacking overall competence in core domains desired more training topics than their competent counterparts (median of 12 topics vs 5, P = .02). In contrast, nonmanagers lacking overall competence desired fewer topics than their competent counterparts (4 vs 6, P < .001). Upper managers with lesser competency in an individual domain often had significantly higher odds of desiring training related to the domain, but the opposite was found for nonmanagers. Among middle managers, little association between competency and training desire was found. CONCLUSIONS: Ideally, lesser competence in core domains would be accompanied by greater desire for ameliorative training, but only upper managers exhibited this pattern. Efforts are needed to better connect domain competency status and training desire among nonmanagers and middle managers.

How scientists interpret and address funding criteria: value creation and undesirable side effects.

Scientists and funding bodies are interdependent actors involved in an ongoing two-way signalling interaction; however, we lack insight on the social mechanisms underpinning this interaction. To address this issue, we examine how successfully funded scientists interpret and address criteria set by the funding body to maximise their chances of funding success. We also consider the possible adverse side effects that can arise from scientists' competitive efforts to address these criteria. Our findings identify a portfolio of funding criteria-research feasibility, research alignment and team credentials-that scientists address when preparing grant applications. Effectively addressing these criteria enhances the prospects of funding success and value creation. However, we also find that scientists can over-address funding criteria, which is counterproductive and yields undesirable side effects. Our research therefore makes an important distinction between the possibilities for value creation and the value creation frictions that can unintentionally arise based on how grant-submitting scientists interpret and address the criteria signalled by the funding body. Our research has implications for policymakers, funding bodies and scientists which we also discuss.

Opioid Consumption After Knee Arthroscopy.

PURPOSE: To prospectively observe opioid consumption in patients undergoing knee arthroscopy and to create an evidence-based guideline for opioid prescription. METHODS: This prospective multicenter observational study enrolled patients undergoing outpatient knee arthroscopy for meniscal repair, meniscectomy, or chondroplasty. Patients were provided with a pain journal to record postoperative opioid consumption, Numeric Pain Rating Scale (NPRS) pain scores, and Likert scale satisfaction scores for 1 week postoperatively. State databases were reviewed for additional opioid prescriptions. RESULTS: One hundred patients were included in this study. Patients were prescribed a median of 5 pills (37.5 oral morphine equivalent [OME]). Median postoperative opioid consumption was 0 pills, with a mean of 0.6 pills (4.4 OME), and 74% of patients did not consume any opioid medication postoperatively. All patients consumed ≤5 pills (37.5 OME), and no patient required a refill. Patients reported a mean daily NPRS value of 1.9 out of 10 and a mean Likert score of 4.4 out of 5. CONCLUSION: We found that current opioid prescribing habits exceed the need for postoperative pain management. Overall, all patients consumed ≤5 opioid pills, and 92% of patients discontinued opioids by the second postoperative day. In spite of the low prescription quantity, patients reported high satisfaction rates and low NPRS pain scores and required no refills. Therefore, we recommend that patients undergoing knee arthroscopy are prescribed no more than 5 oxycodone 5-mg pills. LEVEL OF EVIDENCE: II, prospective prognostic cohort investigation.

Critical role for cholesterol in Lassa fever virus entry identified by a novel small molecule inhibitor targeting the viral receptor LAMP1.

Lassa fever virus (LASV) is endemic in West Africa and causes severe hemorrhagic fever and sensorineural hearing loss. We identified a small molecule inhibitor of LASV and used it to analyze the mechanism of entry. Using a photo-reactive analog that retains antiviral activity as a probe, we identified the inhibitor target as lysosome-associated membrane protein 1 (LAMP1), a host factor that binds to the LASV glycoprotein (GP) during infection. We found that LAMP1 binding to LASV GP is cholesterol-dependent, and that the inhibitor blocks infection by competing with cholesterol in LAMP1. Mutational analysis of a docking-based model identified a putative inhibitor binding site in the cholesterol-binding pocket within the LAMP1 domain that binds GP. These findings identify a critical role for cholesterol in LASV entry and a potential target for therapeutic intervention.

Entrepreneurial ecosystems: economic, technological, and societal impacts.

Despite the overwhelming use of the metaphor 'ecosystem' in academia, industry, policy, and management, exact definitions of what 'ecosystems' really comprise are scarce and often inconsistent. Existing vague descriptions in the literature do not consider the boundaries of respective agglomerations, hence, they impede the evaluation of performance and outcome measures of respective ecosystems. This special issue is a first attempt to trace the 'ecosystem' discussion back to its roots-the ancient oikos, coined by the Greek philosopher Hesiod (700 BC), and aims to critically reflect on the usage of the term 'ecosystem', briefly summarize the extant literature and grasp the main features of entrepreneurial ecosystems, namely the economic, technological, and societal dimensions of entrepreneurial ecosystems. We intend to focus on the key elements that characterize an ecosystem, and hence, untangle under what conditions entrepreneurial firms shape and influence economic, technological, and societal thinking within their ecosystem.

Cigarette Use Among American Indians and Alaska Natives in Metropolitan Areas, Rural Areas, and Tribal Lands.

CONTEXT: Cigarette use among the US general population is significantly lower in metropolitan areas than in rural areas. OBJECTIVE: To assess whether cigarette use among American Indians and Alaska Natives (AI/AN) is lower in metropolitan areas than in rural areas and tribal lands (which are predominantly rural). DESIGN: Data came from the National Survey on Drug Use and Health (2012-2016). Regressions with adjustments for demographics were performed to assess whether cigarette use differed in association with type of place. SETTINGS: The AI/AN in tribal lands (n = 1569), nontribal large metropolitan (1+ million people) areas (n = 582), nontribal small metropolitan (<1 million) areas (n = 1035), and nontribal rural areas (n = 1043). MAIN OUTCOME MEASURES: Cigarette abstinence, current smoking, daily use, number of cigarettes used, and days of use-all in the past month. Nicotine dependence was also examined. RESULTS: Metropolitan (large or small) areas versus rural areas: no statistically significant differences in cigarette use were found. Metropolitan (large or small) areas versus tribal lands: days of cigarette use and daily use were significantly lower in tribal lands. Tribal lands were also lower than small metropolitan areas regarding number of cigarettes used and nicotine dependence. Rural areas versus tribal lands: cigarette measures were consistently lower in tribal lands. For example, the prevalence of current smokers, daily users and nicotine dependence, respectively, was 37.9%, 25.9%, and 16.3% in rural areas and 27.4%, 13.6%, and 8.9% in tribal lands. CONCLUSIONS: Differences in cigarette use between AI/AN in nontribal rural and metropolitan areas were not indicated. Instead, the place differences found were lower cigarette use in tribal lands than in nontribal rural areas and, to some extent, metropolitan areas. These findings can help inform policy makers working to develop context-sensitive anticommercial tobacco efforts for AI/AN.

Evolution without standing genetic variation: change in transgenerational plastic response under persistent predation pressure.

Transgenerational phenotypic plasticity is a fast non-genetic response to environmental modifications that can buffer the effects of environmental stresses on populations. However, little is known about the evolution of plasticity in the absence of standing genetic variation although several non-genetic inheritance mechanisms have now been identified. Here we monitored the pea aphid transgenerational phenotypic response to ladybird predators (production of winged offspring) during 27 generations of experimental evolution in the absence of initial genetic variation (clonal multiplication starting from a single individual). We found that the frequency of winged aphids first increased rapidly in response to predators and then remained stable over 25 generations, implying a stable phenotypic reconstruction at each generation. We also found that the high frequency of winged aphids persisted for one generation after removing predators. Winged aphid frequency then entered a refractory phase during which it dropped below the level of control lines for at least two generations before returning to it. Interestingly, the persistence of the winged phenotype decreased and the refractory phase lasted longer with the increasing number of generations of exposure to predators. Finally, we found that aphids continuously exposed to predators for 22 generations evolved a significantly weaker plastic response than aphids never exposed to predators, which, in turn, increased their fitness in presence of predators. Our findings therefore showcased an example of experimental evolution of plasticity in the absence of initial genetic variation and highlight the importance of integrating several components of non-genetic inheritance to detect evolutionary responses to environmental changes.

Topical Drug Delivery to the Posterior Segment of the Eye: Addressing the Challenge of Preclinical to Clinical Translation.

Topical delivery of therapeutics to the posterior segment of the eye remains the "holy grail" of ocular drug delivery. As an example, anti-vascular endothelial growth factor biologics, such as ranibizumab, aflibercept, and bevacizumab, are delivered by intravitreal injection to treat neovascular age-related macular degeneration and, although these drugs have revolutionized treatment of the disease, less invasive alternatives to intravitreal injection are desired. Multiple reports in the literature have demonstrated topical delivery of both small and large molecules to the back of the eye in small animal models. Despite this progress, successful translation to larger species, and ultimately humans, has yet to be demonstrated. Selection of animal models with relevant ocular anatomy and physiology, along with appropriate experimental design, is critical to enable more relevant feasibility assessments and increased probability of successful translation.

Pharmaceutical Development of AAV-Based Gene Therapy Products for the Eye.

A resurgence of interest and investment in the field of gene therapy, driven in large part by advances in viral vector technology, has recently culminated in United States Food and Drug Administration approval of the first gene therapy product targeting a disease caused by mutations in a single gene. This product, LUXTURNA™ (voretigene neparvovec-rzyl; Spark Therapeutics, Inc., Philadelphia, PA), delivers a normal copy of the RPE65 gene to retinal cells for the treatment of biallelic RPE65 mutation-associated retinal dystrophy, a blinding disease. Many additional gene therapy programs targeting both inherited retinal diseases and other ocular diseases are in development, owing to an improved understanding of the genetic basis of ocular disease and the unique properties of the ocular compartment that make it amenable to local gene therapy. Here we review the growing body of literature that describes both the design and development of ocular gene therapy products, with a particular emphasis on target and vector selection, and chemistry, manufacturing, and controls.

Impacts of Canada's minimum age for tobacco sales (MATS) laws on youth smoking behaviour, 2000-2014.

BACKGROUND: Recently, the US Institute of Medicine has proposed that raising the minimum age for tobacco purchasing/sales to 21 years would likely lead to reductions in smoking behavior among young people. Surprisingly few studies, however, have assessed the potential impacts of minimum-age tobacco restrictions on youth smoking. OBJECTIVE: To estimate the impacts of Canadian minimum age for tobacco sales (MATS) laws on youth smoking behaviour. DESIGN: A regression-discontinuity design, using seven merged cycles of the Canadian Community Health Survey, 2000-2014. PARTICIPANTS: Survey respondents aged 14-22 years (n=98 320). EXPOSURE: Current Canadian MATS laws are 18 years in Alberta, Saskatchewan, Manitoba, Quebec, the Yukon and Northwest Territories, and 19 years of age in the rest of the country. MAIN OUTCOMES: Current, occasional and daily smoking status; smoking frequency and intensity; and average monthly cigarette consumption. RESULTS: In comparison to age groups slightly younger than the MATS, those just older had significant and abrupt increases immediately after the MATS in the prevalence of current smokers (absolute increase: 2.71%; 95% CI 0.70% to 4.80%; P=0.009) and daily smokers (absolute increase: 2.43%; 95% CI 0.74% to 4.12%; P=0.005). Average past-month cigarette consumption within age groups increased immediately following the MATS by 18% (95% CI 3% to 39%; P=0.02). There was no evidence of significant increases in smoking intensity for daily or occasional smokers after release from MATS restrictions. CONCLUSION: The study provides relevant evidence supporting the effectiveness of Canadian MATS laws for limiting smoking among tobacco-restricted youth.

Interaction rewiring and the rapid turnover of plant-pollinator networks.

Whether species interactions are static or change over time has wide-reaching ecological and evolutionary consequences. However, species interaction networks are typically constructed from temporally aggregated interaction data, thereby implicitly assuming that interactions are fixed. This approach has advanced our understanding of communities, but it obscures the timescale at which interactions form (or dissolve) and the drivers and consequences of such dynamics. We address this knowledge gap by quantifying the within-season turnover of plant-pollinator interactions from weekly censuses across 3 years in a subalpine ecosystem. Week-to-week turnover of interactions (1) was high, (2) followed a consistent seasonal progression in all years of study and (3) was dominated by interaction rewiring (the reassembly of interactions among species). Simulation models revealed that species' phenologies and relative abundances constrained both total interaction turnover and rewiring. Our findings reveal the diversity of species interactions that may be missed when the temporal dynamics of networks are ignored.

Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection.

Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection and in many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV. Here we report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection. Using mutant cell lines and informative derivatives of the lead compound, we show that the target of the inhibitor is the endosomal membrane protein Niemann-Pick C1 (NPC1). We find that NPC1 is essential for infection, that it binds to the virus glycoprotein (GP), and that antiviral compounds interfere with GP binding to NPC1. Combined with the results of previous studies of GP structure and function, our findings support a model of EboV infection in which cleavage of the GP1 subunit by endosomal cathepsin proteases removes heavily glycosylated domains to expose the amino-terminal domain, which is a ligand for NPC1 and regulates membrane fusion by the GP2 subunit. Thus, NPC1 is essential for EboV entry and a target for antiviral therapy.

Considerations for practice-based research: a cross-sectional survey of chiropractic, acupuncture and massage practices.

BACKGROUND: Complementary and alternative medicine (CAM) use has steadily increased globally over the past two decades and is increasingly playing a role in the healthcare system in the United States. CAM practice-based effectiveness research requires an understanding of the settings in which CAM practitioners provide services. This paper describes and quantifies practice environment characteristics for a cross-sectional sample of doctors of chiropractic (DCs), licensed acupuncturists (LAcs), and licensed massage therapists (LMTs) in the United States. METHODS: Using a cross-sectional telephone survey of DCs (n = 32), LAcs (n = 70), and LMTs (n = 184) in the Tucson, AZ metropolitan area, we collected data about each location where practitioners work, as well as measures on practitioner and practice characteristics including: patient volume, number of locations where practitioners worked, CAM practitioner types working at each location, and business models of practice. RESULTS: The majority of practitioners reported having one practice location (93.8% of DCs, 80% of LAcs and 59.8% of LMTs) where they treat patients. Patient volume/week was related to practitioner type; DCs saw 83.13 (SD = 49.29) patients/week, LAcs saw 22.29 (SD = 16.88) patients/week, and LMTs saw 14.21 (SD =10.25) patients per week. Practitioners completed surveys for N = 388 practice locations. Many CAM practices were found to be multidisciplinary and/or have more than one practitioner: 9/35 (25.7%) chiropractic practices, 24/87 (27.6%) acupuncture practices, and 141/266 (53.0%) massage practices. Practice business models across CAM practitioner types were heterogeneous, e.g. sole proprietor, employee, partner, and independent contractor. CONCLUSIONS: CAM practices vary across and within disciplines in ways that can significantly impact design and implementation of practice-based research. CAM research and intervention programs need to be mindful of the heterogeneity of CAM practices in order to create appropriate interventions, study designs, and implementation plans.

Efficacy of topical benzoyl peroxide on the reduction of Propionibacterium acnes during shoulder surgery.

BACKGROUND: Propionibacterium acnes infection is a significant problem after shoulder surgery. Residual P. acnes is found on the skin up to 29% of the time immediately after surgical skin preparation and in 70% of dermal biopsy specimens. These residual bacteria may be a source for infection. Identifying more ideal skin preparation may help reduce the risk of infection. The purpose of this study was to evaluate the effect that topical benzoyl peroxide (BPO), with chlorhexidine skin preparation, would have on the presence of P. acnes cultured at the time of shoulder surgery. We hypothesized that adding topical BPO to our skin preparation would reduce the number of positive P. acnes cultures identified during surgery. METHODS: Fifty patients undergoing first-time shoulder surgery were treated with topical 5% BPO cream 48 hours before surgery. After skin preparation, 13 samples per subject were obtained. Cultures were held for 14 days. RESULTS: Fifty patients underwent arthroscopic shoulder surgery; 650 culture specimens were obtained. The skin was positive at the initiation of surgery in 6% of cases. Tissue samples were positive in 6%. The skin was positive in 10% at the end of surgery. None of these rates of positive culture were different from the 4% rate observed with a control swab. CONCLUSION: Application of BPO is an effective way to reduce P. acnes on skin at the beginning and, importantly, at the end of a surgical procedure. This may result in a lower risk for postoperative infection.

Presence of Propionibacterium acnes in primary shoulder arthroscopy: results of aspiration and tissue cultures.

BACKGROUND: Infection after shoulder surgery has a serious impact on patient outcome and costs associated with care. Propionibacterium acnes infection may be insidious and manifest years after index surgery with resultant joint arthropathy or prosthesis infection. Our goal was to evaluate the presence of P. acnes in a group of patients undergoing primary arthroscopic shoulder surgery to better understand this organism. METHODS: Samples were collected from 57 patients undergoing first-time shoulder arthroscopy. Demographic data and medical comorbidities were collected. A control, 2 skin swabs, synovial fluid, and 3 tissue samples were obtained. All samples were placed on aerobic plates, on anaerobic plates, and in thioglycolate broth and held for 28 days. RESULTS: Fifty-seven patients underwent arthroscopic shoulder surgery. The mean age was 51 years. Eighty-one samples (21.8%) were positive for P. acnes when cultures were held 14 days; 32 subjects (56%) had at least 1 culture that grew P. acnes. Positive skin cultures for P. acnes increased from 15.8% before incision to 40.4% at closure. This was even more pronounced in men as positive skin cultures increased from 31.3% before incision to 63.0% at closure. Thirteen patients (22.8%) had more than 3 cultures positive. None of the patients in this study have had signs or symptoms to suggest clinical P. acnes infection. CONCLUSIONS: Of all subjects studied, 56% had at least 1 positive culture; 21% (of all 371 culture specimens obtained) grew P. acnes. We suspect that it is a consequence of true positive cultures from imperfect skin preparation and dermal contamination.

Tobacco brief intervention training for chiropractic, acupuncture, and massage practitioners: protocol for the CAM reach study.

BACKGROUND: Tobacco use remains the leading cause of morbidity and mortality in the US. Effective tobacco cessation aids are widely available, yet underutilized. Tobacco cessation brief interventions (BIs) increase quit rates. However, BI training has focused on conventional medical providers, overlooking other health practitioners with regular contact with tobacco users. The 2007 National Health Interview Survey found that approximately 20% of those who use provider-based complementary and alternative medicine (CAM) are tobacco users. Thus, CAM practitioners potentially represent a large, untapped community resource for promoting tobacco cessation and use of effective cessation aids. Existing BI training is not well suited for CAM practitioners' background and practice patterns, because it assumes a conventional biomedical foundation of knowledge and philosophical approaches to health, healing and the patient-practitioner relationship. There is a pressing need to develop and test the effectiveness of BI training that is both grounded in Public Health Service (PHS) Guidelines for tobacco dependence treatment and that is relevant and appropriate for CAM practitioners. METHODS/DESIGN: The CAM Reach (CAMR) intervention is a tobacco cessation BI training and office system intervention tailored specifically for chiropractors, acupuncturists and massage therapists. The CAMR study utilizes a single group one-way crossover design to examine the CAMR intervention's impact on CAM practitioners' tobacco-related practice behaviors. Primary outcomes included CAM practitioners' self-reported conduct of tobacco use screening and BIs. Secondary outcomes include tobacco using patients' readiness to quit, quit attempts, use of guideline-based treatments, and quit rates and also non-tobacco-using patients' actions to help someone else quit. DISCUSSION: CAM practitioners provide care to significant numbers of tobacco users. Their practice patterns and philosophical approaches to health and healing are well suited for providing BIs. The CAMR study is examining the impact of the CAMR intervention on practitioners' tobacco-related practice behaviors, CAM patient behaviors, and documenting factors important to the conduct of practice-based research in real-world CAM practices.

Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences.

Filoviruses are enveloped viruses that cause sporadic outbreaks of severe hemorrhagic fever [CDC, MMWR Morb. Mortal. Wkly. Rep. 50:73-77, 2001; Colebunders and Borchert, J. Infect. 40:16-20, 2000; Colebunders et al., J. Infect. Dis. 196(Suppl. 2):S148-S153, 2007; Geisbert and Jahrling, Nat. Med. 10:S110-S121, 2004]. Previous studies revealed that endosomal cysteine proteases are host factors for ebolavirus Zaire (Chandran et al., Science 308:1643-1645, 2005; Schornberg et al., J. Virol. 80:4174-4178, 2006). In this report, we show that infection mediated by glycoproteins from other phylogenetically diverse filoviruses are also dependent on these proteases and provide additional evidence indicating that they cleave GP1 and expose the binding domain for the critical host factor Niemann-Pick C1. Using selective inhibitors and knockout-derived cell lines, we show that the ebolaviruses Zaire and Cote d'Ivoire are strongly dependent on cathepsin B, while the ebolaviruses Sudan and Reston and Marburg virus are not. Taking advantage of previous studies of cathepsin B inhibitor-resistant viruses (Wong et al., J. Virol. 84:163-175, 2010), we found that virus-specific differences in the requirement for cathepsin B are correlated with sequence polymorphisms at residues 47 in GP1 and 584 in GP2. We applied these findings to the analysis of additional ebolavirus isolates and correctly predicted that the newly identified ebolavirus species Bundibugyo, containing D47 and I584, is cathepsin B dependent and that ebolavirus Zaire-1995, the single known isolate of ebolavirus Zaire that lacks D47, is not. We also obtained evidence for virus-specific differences in the role of cathepsin L, including cooperation with cathepsin B. These studies strongly suggest that the use of endosomal cysteine proteases as host factors for entry is a general property of members of the family Filoviridae.

Effects of the minimum legal drinking age on alcohol-related health service use in hospital settings in Ontario: a regression-discontinuity approach.

OBJECTIVES: We assessed the impact of the minimum legal drinking age (MLDA) on hospital-based treatment for alcohol-related conditions or events in Ontario, Canada. METHODS: We conducted regression-discontinuity analyses to examine MLDA effects with respect to diagnosed alcohol-related conditions. Data were derived from administrative records detailing inpatient and emergency department events in Ontario from April 2002 to March 2007. RESULTS: Relative to youths slightly younger than the MLDA, youths just older than the MLDA exhibited increases in inpatient and emergency department events associated with alcohol-use disorders (10.8%; P = .048), assaults (7.9%; P < .001), and suicides related to alcohol (51.8%; P = .01). Among young men who had recently crossed the MLDA threshold, there was a 2.0% increase (P = .01) in hospitalizations for injuries. CONCLUSIONS: Young adults gaining legal access to alcohol incur increases in hospital-based care for a range of serious alcohol-related conditions. Our regression-discontinuity approach can be used in future studies to assess the effects of the MLDA across different settings, and our estimates can be used to inform cost-benefit analyses across MLDA scenarios.