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Background The impact of lumacaftor/ivacaftor on exercise tolerance in people with cystic fibrosis (CF) has not been thoroughly studied. Methods We conducted a multisite Phase 4 trial comparing the impact of lumacaftor/ivacaftor on exercise tolerance with that of placebo in participants ≥ 12 years of age with CF homozygous for F508del-CFTR. The primary endpoint was relative change from baseline in maximum oxygen consumption (VO2max) during cardiopulmonary exercise testing (CPET) at Week 24. The key secondary endpoint was relative change from baseline in exercise duration during CPET at Week 24. Other secondary endpoints included changes in other indices of exercise tolerance and changes in CF assessments; safety and tolerability were assessed as an endpoint. Results Seventy participants were randomized to receive lumacaftor/ivacaftor (n = 34) or placebo (n = 36). The least-squares mean difference for lumacaftor/ivacaftor versus placebo in relative change in VO2max from baseline at Week 24 was −3.2% (95% CI: −9.2, 2.9; P=0.3021); the least-squares mean difference in relative change from baseline in exercise duration at Week 24 was −3.2% (95% CI: −8.0, 1.6). Safety results were consistent with the known lumacaftor/ivacaftor safety profile. Conclusions Definitive conclusions regarding the impact of lumacaftor/ivacaftor on exercise tolerance cannot be drawn from these results; however, multicenter studies using CPETs can be reliably performed with multiple time points and conventional methods, provided that calibration can be achieved. Future studies of exercise tolerance may benefit from lessons learned from this study. NCT02875366.

The management of multidrug-resistant tuberculosis (MDR TB) is notably complex among patients with human immunodeficiency virus (HIV). TB treatment recommendations typically include very little information specific to HIV and MDR TB, which often is derived from clinical trials conducted in low-resource settings. Mortality rates among patients with HIV and MDR TB remain high. We reviewed the published literature and recommendations to synthesize possible patient management approaches demonstrated to improve treatment outcomes in high-resourced countries for patients with MDR TB and HIV. Approaches to diagnostic testing, impact and timing of antiretroviral therapy on mortality, anti-MDR TB and antiretroviral drug interactions, and the potential role for short-course MDR TB therapy are examined. The combination of antiretroviral therapy with expanded TB drug therapy, along with the management of immune reconstitution inflammatory syndrome, other potential HIV-associated opportunistic diseases, and drug toxicities, necessitate an integrated multidisciplinary patient care approach using public health case management and provider expertise in drug-resistant TB and HIV management.

Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2-fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.

Gonorrhea is caused by Neisseria gonorrhoeae. For men, classic manifestations of gonorrhea include urethritis and oropharyngeal exudates with lymphadenopathy. In women, classic manifestations are cervicitis, infertility, ectopic pregnancy, chronic pelvic pain, and pelvic inflammatory disease, but women commonly may be asymptomatic. Nucleic acid amplification test is preferred for diagnosing genital and extragenital gonococcal infections. Ceftriaxone cures about 98%-99% of uncomplicated gonorrhea infections, but dual treatment with ceftriaxone and azithromycin is recommended. Retesting is recommended 3 months after treatment because patients with gonorrhea constitute a high-risk group with potential for reinfection.

Background Immunocompromised individuals are at risk for Nocardia infection, with a recurrence rate of approximately 5%. Solid organ transplant (SOT) recipients often receive secondary prophylaxis due to their requirement of lifelong immunosuppression. However, data supporting this practice is sparse. We sought to evaluate Nocardia recurrence in SOT recipients, specifically evaluating secondary prophylaxis. Methods We conducted a retrospective cohort study of SOT recipients diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy and had at least 6 months of post-therapy follow-up. The primary outcome was Nocardia recurrence, which included relapse and reinfection. Results 102 patients met inclusion criteria. Sixty-six (64.7%) were male and mean age was 58.6±11.7 years. Most common SOT types were kidney (46.1%), heart (18.6%), kidney-pancreas (11.8%), and lung (10.8%). Most common sites of infection were lung (85.3%), skin (17.6%), and brain (14.7%). Secondary prophylaxis was utilized in 53 (52.0%) patients. TMP-SMX single-strength daily was the most common prophylaxis agent and dose. Five patients (4.9%) experienced Nocardia recurrence, 3 of which were receiving secondary prophylaxis at time of recurrence. Two recurrences were with the same Nocardia species. Factors associated with recurrence were lung transplantation (p = 0.011), chronic lung disease (p = 0.032), and treatment ≤ 120 days (p = 0.006). Time from treatment completion to recurrence ranged from 107 to 875 days. Conclusions Nocardia recurrence in SOT recipients is an uncommon event. TMP-SMX secondary prophylaxis is incompletely protective and recurrence may be dependent upon other factors. Further study of secondary prophylaxis is warranted. This article is protected by copyright. All rights reserved.

Fungal infections within the central nervous system (CNS) occur more commonly in patients with immunosuppressive conditions but occasionally are diagnosed in immunocompetent patients as well. This may reflect the route of infection and the specific pathogen. Fungal infections resulting from hematogenous seeding are typically encountered in patients with profound and prolonged immunosuppression (including neutropenia); however, pathogens such as Cryptococcus gattii and some dimorphic fungi can also produce CNS disease in otherwise healthy persons. A common avenue of infection in immunocompetent patients is traumatic or nosocomial inoculation, including neurosurgical procedures, foreign body implants, and contaminated spinal fluid injections.

BACKGROUND Exercise testing is important in people with cystic fibrosis (pwCF). The aim was to develop an incremental maximal step test to assess exercise capacity across the range of pwCF, without floor or ceiling effects, within restrictions of space, and infection prevention. METHODS The step test was developed in adults with stable CF. Subjects assisted in selecting: step height, start rate, increments, stage and test duration parameters. Equipment to externally pace and time the test and measure exercise parameters were selected. Reasons for stopping, criteria for achieving a maximal test, and key outcome measures were determined. Documentation to record and standardize the test and instructions to set up the metronome and timer App were developed. Infection control practices were considered. RESULTS Eight subjects were recruited to develop the Alfred Step Test Exercise Protocol (A-STEP) on a 20 cm portable step. The A-STEP package included a pretest information sheet, clinical assessment and instructions, recording worksheet, and the metronome/timer instructions. The test started at 18 steps/min. Each level increased by two steps/min to a maximum of 48 steps (Level 16). Results were presented as mean (SD) [range] for: age 30.63 (5.89) [21-39] years; FEV1 58.13 (18.33) [32-89]%; levels: 10.31 (3.29) [6-15.5]. The A-STEP required space of 2 m2 and complied with current infection control guidelines. CONCLUSIONS The A-STEP is a new incremental maximal step test to assess exercise capacity in pwCF, without floor or ceiling effects. It addresses the issues of space restrictions and the need for strict infection prevention in the clinical setting.

Accurately quantifying species’ area requirements is a prerequisite for effective area‐based conservation. This typically involves collecting tracking data on species of interest and then conducting home‐range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home‐range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross‐validation to quantify bias in empirical home‐range estimates. Area requirements of mammals 1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum., Article impact statement: Due to autocorrelation‐induced bias, conventional methods severely underestimate the area requirements of GPS‐tracked large mammals.

Grade 91 steels have been used in power generation for more than 20 years in high temperature, high pressure applications such as steam piping, headers and tubing because it provides superior creep and oxidation resistance at elevated temperatures. The mechanical properties of the material are dependent on the creation of a martensitic microstructure, however incorrect heat treatment during manufacture, installation or repair can result in a weak ferritic or semi-ferritic microstructure which can cause premature component failure. Currently, components with incorrect, weak microstructures are identified using hardness testing; a manual technique which is prone to error. This work details a series of tests carried out at the University of Manchester to assess the suitability of multi-parameter magnetic testing for the identification of incorrect microstructures. The tests stem from a workshop organized by the Electric Power Research Institute (EPRI) where three sets of samples (eight pipe sections, eight tube sections and eight unidentified tube sections) with different microstructures were circulated world-wide. The results of the work show that the magnetic measurement techniques employed in these tests have the potential to provide a basis for the development of a portable NDE system for the identification of incorrect microstructures in Grade 91 plant components. The developed system would enable fast scanning of components with very little surface preparation along with digital data storage, improving on current manual hardness testing.

Nontuberculous mycobacteria (NTM) comprise a heterogeneous group of organisms, with only a small subset known to cause disease in humans. Although NTM infection is not a reportable disease, both the increasing clinical recognition and recent advancements in laboratory diagnostic capabilities of NTM infections in immunocompromised and immunocompetent patients are rapidly evolving. We reviewed antimicrobial agents used to treat the most frequently encountered NTM infections and examined optimized drug dosing strategies, toxicity profiles, drug-drug interactions, and the role of therapeutic drug monitoring. Antimicrobial susceptibility testing and patient monitoring on therapy were also examined. We used PubMed to review the published literature on the management of select NTM pathogens, the common syndromes encountered since 2000, and select pharmacokinetic principles of select antimicrobial agents used since 1990. We included select clinical trials, systematic reviews, published guidelines, and observational studies when applicable. The prolonged duration and the necessity for combination therapy for most forms of NTM disease can be problematic for many patients. A multidisciplinary care team that includes pharmacy engagement may help increase rates of optimal patient tolerability and successful treatment completion.

Introduction: Mycobacterium scrofulaceum infection has been identified in cases of paediatric cervical lymphadenitis but is less well defined in adults. To further characterize manifestations of M....

Objectives To determine in women with clinically stable chronic lung disease (CLD) and healthy women; (1) prevalence of urinary incontinence; (2) risk factors for urinary incontinence; (3) effects of a standard course of specialised physiotherapy treatment (PT) in women with CLD. Design Prospective prevalence study; PT study in CLD subgroup. Setting Tertiary metropolitan public hospital. Participants Women with cystic fibrosis (CF, n = 38), chronic obstructive pulmonary disease (COPD, n = 27) and 69 healthy women without CLD. PT study — 10 women with CLD. Interventions Five continence PT sessions over 3 months. Main outcome measures Prevalence and impact of incontinence (questionnaire), number of leakage episodes (7-day accident diary), pelvic floor muscle function (ultrasound imaging) and quality of life (King’s Health Questionnaire). Results The majority of women in all three groups reported episodes of incontinence (CF 71%; COPD 70%; healthy women 55%). Compared to age-matched healthy controls, women with CF reported more episodes of incontinence (P = 0.006) and more commonly reported stress incontinence (P = 0.001). A logistic regression model revealed that women with CLD were twice as likely to develop incontinence than healthy women (P = 0.05). Women with COPD reported significantly more ‘bother’ with incontinence than age-matched women with incontinence. There was a significant reduction in incontinence episodes following treatment, which was maintained after three months. Conclusions The presence of CLD is an independent predictor of incontinence in women. In older women this is associated with more distress than in age-matched peers without CLD. Larger treatment studies are indicated for women with CLD and incontinence.

BACKGROUND: The objective of the study was to provide estimates of and risk factors for engagement in LTBI care in the overall U.S. population and among specific risk groups. METHODS: We used nationally representative data from 7,080 participants in the 2011-2012 National Health and Nutrition Examination Survey. Engagement in LTBI care was assessed by estimating the proportion with a history of testing, diagnosis, treatment initiation and treatment completion. Weighted methods were used to account for the complex survey design and to derive national estimates. RESULTS: Only 1.4 million (10%) of an estimated 14.0 million individuals with LTBI had previously completed treatment. Of the 12.6 million who did not complete LTBI treatment, 3.7 million (29%) had never been tested and 7.2 million (57%) received testing but had no history of diagnosis. High-risk groups showed low levels of engagement, including TB contacts and persons born outside the United States. CONCLUSIONS AND RELEVANCE: There is a reservoir of more than 12 million individuals in the U.S. who may be at risk for progression to TB disease and potential transmission. TB control programs and community providers should consider focused efforts to increase testing, diagnosis, and treatment for LTBI.

Rationale: Current diagnostic tests fail to identify individuals at higher risk of progression to tuberculosis disease, such as those with recent Mycobacterium tuberculosis infection, who should be prioritized for targeted preventive treatment. Objectives: To define a blood-based biomarker, measured with a simple flow cytometry assay, that can stratify different stages of tuberculosis infection to infer risk of disease. Methods: South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion 1 yr) infection. We defined the ΔHLA-DR median fluorescence intensity biomarker as the difference in HLA-DR expression between IFN-γ+ TNF+ Mycobacterium tuberculosis–specific T cells and total CD3+ T cells. Biomarker performance was assessed by blinded prediction in untouched test cohorts with recent versus persistent infection or tuberculosis disease and by unblinded analysis of asymptomatic adolescents with tuberculosis infection who remained healthy (nonprogressors) or who progressed to microbiologically confirmed disease (progressors). Measurements and Main Results: In the test cohorts, frequencies of Mycobacterium tuberculosis–specific T cells differentiated between QuantiFERON-TB− (n = 25) and QuantiFERON-TB+ (n = 47) individuals (area under the receiver operating characteristic curve, 0.94; 95% confidence interval, 0.87–1.00). ΔHLA-DR significantly discriminated between recent (n = 20) and persistent (n = 22) QuantiFERON-TB+ (0.91; 0.83–1.00); persistent QuantiFERON-TB+ and newly diagnosed tuberculosis (n = 19; 0.99; 0.96–1.00); and tuberculosis progressors (n = 22) and nonprogressors (n = 34; 0.75; 0.63–0.87). However, ΔHLA-DR median fluorescent intensity could not discriminate between recent QuantiFERON-TB+ and tuberculosis (0.67; 0.50–0.84). Conclusions: The ΔHLA-DR biomarker can identify individuals with recent QuantiFERON-TB conversion and those with disease progression, allowing targeted provision of preventive treatment to those at highest risk of tuberculosis. Further validation studies of this novel immune biomarker in various settings and populations at risk are warranted.

Mycobacterium septicum is a rarely identified nontuberculous mycobacterium capable of causing infections in both healthy and immunocompromised individuals. Only a few cases of M. septicum infections have been reported, which makes recognizing corresponding clinical disease more challenging for clinicians. Antimicrobial susceptibility profiles for this organism are not well described, and corresponding optimal therapeutic regimens have not been established. We report a tertiary care center’s experience with M. septicum from 2014 to 2020. Twelve adult patients with positive cultures for M. septicum were identified. Most cases were identified from sputum samples of individuals with underlying lung disease. Most cases involving M. septicum isolation in culture were not felt to be clinically significant. Two cases were considered possible infections, while only one case was considered a definite infection that required antimicrobial treatment. All M. septicum isolates were susceptible in vitro to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole. Isolates were universally resistant to clarithromycin and doxycycline. The isolation of M. septicum in culture is uncommon and requires clinical correlation to determine its clinical relevance and need for treatment. Susceptibility testing should be performed to guide therapy.

Objectives In patients with cystic fibrosis (CF) who carry the G551D mutation, treatment with ivacaftor improves lung function and weight; however, short- and long-term impacts on body composition have not been well studied. Methods Twenty adults with CF carrying the G551D mutation (mean ± standard deviation body mass index [BMI] 23.3 ± 4.3 kg/m2) were recruited for a single-center, double-blind, placebo-controlled, 28-d, crossover study of ivacaftor, followed by an open-label extension (OLE) for 5 mo. Eleven patients underwent measurements 2 y later. The study variables included weight, BMI, and body composition (including fat-free mass [FFM] and fat mass). Results After 28 d of treatment with ivacaftor, weight increased by 1.1 ± 1.3 kg, BMI by 0.4 ± 0.5 kg/m2, and FFM by 1.1 ± 1.2 kg (all P Conclusions Small gains were seen in FFM in the first month of ivacaftor treatment. Weight, BMI, and fat-mass gains in the first 6 mo on ivacaftor plateaued by 2.5 y. The metabolic and clinical consequences of weight and fat-mass gains remain to be determined.

International audience; The overlap in the mass symmetric region of the reaction products from fusion-fission and quasifission complicates the assignment of symmetric events to complete fusion on the basis of the mass distribution alone. Additional observables, besides mass distribution, should be used. The approach proposed here relies on the fact that fusion-fission and quasifission are characterized by different timescales. Within this framework, we performed a detailed study to find out how timescales can be probed via angular momentum transfer as measured via γ-ray multiplicities. The proof of principle was carried out by measuring the γ rays in coincidence with fusion-fission and quasielastic binary fragments in the reaction S32 + Au197 at beam energy near the Coulomb barrier. The experiment was performed at the Accélérateur Linéaire Tandem à Orsay (ALTO) facility at the Institut De Physique Nucléaire (IPN) in Orsay (France) using a detection setup consisting of ORGAM (ORsay GAMma) and PARIS (Photon Array Radioactive Ion Stable beams) γ-detectors arrays coupled with the CORSET (CORrelation SETup) time-of-flight spectrometer. Results of the sensitivity of this method to distinguish reaction channels with different dynamics are discussed.

NASA's deterministic transport code HZETRN, and its three-dimensional (3D) counterpart, 3DHZETRN, are being used to characterize the space radiation environment over a wide range of scenarios, including future planned missions to the moon or Mars. Combined with available spaceflight measurements, these tools provide the fundamental input for risk models used to quantify possible astronaut health decrements and satisfy agency limits in support of exploration initiatives. Further research is therefore needed to improve radiation transport and nuclear physics models while at the same time continuing to expand the available measurement database (ground-based and spaceflight) to validate such efforts. In this work, significant updates to the deterministic radiation transport models are presented. Charged muons and pions are fully coupled with the existing solutions developed for neutron and light ion (Z ≤ 2) transport. This update includes the 3D nature of pion production as well as the pion interactions, resulting in further production of energetic nucleons within shielding. Additional updates related to low energy proton recoils in hydrogenous materials and capture/decay processes associated with charged pions at rest are also described. Included in this work is the coupling of single and double-differential cross sections from Geant4 into HZETRN and 3DHZETRN. This enables a direct comparison of deterministic and Monte Carlo transport methodologies using the same nuclear databases for specific interactions. Comparisons between Geant4 and 3DHZETRN are shown and establish that the transport methodologies are in excellent agreement when the same cross sections are used. The deterministic codes are also compared to ISS data, and it is found that the updated 3D procedures are within measurement uncertainty (±5%) at cutoff rigidities below 1 GV, which approaches free space conditions.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which presents an unprecedented challenge to medical providers worldwide. Although most SARS-CoV-2-infected individuals manifest with a self-limited mild disease that resolves with supportive care in the outpatient setting, patients with moderate to severe COVID-19 will require a multidisciplinary collaborative management approach for optimal care in the hospital setting. Laboratory and radiologic studies provide critical information on disease severity, management options, and overall prognosis. Medical management is mostly supportive with antipyretics, hydration, oxygen supplementation, and other measures as dictated by clinical need. Among its medical complications is a characteristic proinflammatory cytokine storm often associated with end-organ dysfunction, including respiratory failure, liver and renal insufficiency, cardiac injury, and coagulopathy. Specific recommendations for the management of these medical complications are discussed. Despite the issuance of emergency use authorization for remdesivir, there are still no proven effective antiviral and immunomodulatory therapies, and their use in COVID-19 management should be guided by clinical trial protocols or treatment registries. The medical care of patients with COVID-19 extends beyond their hospitalization. Postdischarge follow-up and monitoring should be performed, preferably using telemedicine, until the patients have fully recovered from their illness and are released from home quarantine protocols.

3DHZETRN-v2 includes a detailed three dimensional (3D) treatment of neutron/light-ion transport based on a quasi-elastic/multiple production assumption allowing improved agreement of the neutron/light-ion fluence compared with results of three Monte Carlo (MC) codes in the sense that the variance with respect to the individual MC results is less than the variance among the MC code results. The current numerical methods are no longer the main limitation to HZETRN code development and further changes in the nuclear model are required. In a prior study, an improved quasi-elastic spectrum based on a solution of the transport approximation to nuclear media effects showed promise, but the remaining multiple-production spectrum was based on a database derived from the Ranft model that used Bertini multiplicities. In the present paper, we will implement a more complete Serber first step into the 3DHZETRN-v2 code, but we retain the Bertini-Ranft branching ratios and evaporation multiplicities. It is shown that the new Serber model in the 3HZETRN-v2 code reduces the variance with individual MC codes, which are largely due to nuclear cross section model differences. The code will be available through the software system, OLTARIS, for shield design and validation and provides a basis for personal computer software capable of space shield analysis and optimization.

Engineering technology plays a pivotal role in the delivery of health care in under-resourced countries by providing an infrastructure to improve patient outcomes. However, sustainability of these technologies is difficult in these settings oftentimes due to limited resources or training. The framework presented in this editorial focuses on establishing medical and laboratory equipment sustainability in developing countries and is comprised of four steps: 1) establishing reliable in-country relationships with stakeholders, 2) identifying needs for sustainable solutions locally, 3) exploring potential solutions and assessing their effort-to-impact ratios, and 4) working with strategic partners to implement solutions with clear performance metrics. By focusing on the sustainability of donated equipment instead of the equipment itself, this method presented distinguishes itself from other philanthropic endeavors in the field by seeking to establish preventive maintenance habits that can impact clinical outcomes of a community long term. Application of this methodology is reported in the Original Research Article “A Low-Cost Humidity Control System to Protect Microscopes in a Tropical Climate” by Asp et. al.

Cardiovascular device infection due to rapidly growing mycobacteria (RGM) is rarely encountered in clinical practice. Due to the increasing number of indications and use of cardiovascular devices in an aging population, optimized management of these infections is of great importance. We report seven cases of RGM cardiovascular device infection. Three patients had left-ventricular assist device (LVAD) infections; two patients had cardiovascular implantable device (CIED) infections; and one had an aortic vascular stent infection. Specific cardiac valvular infection was not detected among any of the patients. All patients had a high number of comorbidities which limited some patients from receiving optimal combination antimicrobial therapy. The prognosis of cardiovascular device infections with RGM is guarded with only four patients still alive; however, the treatment approach for each patient varied considerably and often based on concurrent medical conditions, overall adjustments to goals of care, and specific patient preferences. Further analysis of cardiovascular device infections with RGM is warranted to establish a more systematic approach in successful management.

The relevance of medical colleges has been questioned and their ability to respond to members' needs and system failures is unknown. We hypothesise that members believe that medical colleges are relevant to the current health agenda. We conducted a survey by email to determine satisfaction with the current state of the Royal Australasian College of Physicians (RACP) relevance and tested agreement with suggestions for change. We found that of 21 000 survey links sent, 13.1% of addressees replied. When questioned regarding the current state, less than 50% of respondents agreed with any of eight positive statements. Over two thirds supported involvement in policy and advocacy, as well as the use of digital plebiscites to express their views. Clarity around the use of members' subscriptions and value for money had the lowest scores. Of importance was the expression of need for a medical college (71%) and the finding that 58% of respondents would give more time to the RACP if asked. Of all respondents, 22% provided written comments that closely reflected scores on categorical questions. We conclude that, despite reported disengagement and lack of support for the current state, the majority of respondents to a survey of relevance believed in the need for a medical college.

In people with cystic fibrosis (CF) reduced fitness and lower levels of physical activity have been associated with poorer prognosis [1] and greater decline in lung function [2]. Despite the health benefits of being physically active [3], in people with CF adherence to exercise programmes is often poor [4], and prescribed exercise training programmes have seldom translated into increased daily physical activity [5]., Achieving physical activity guidelines by undertaking multiple bouts of moderate-vigorous physical activity ≥10 min duration, but not shorter periods of activity, was independently associated with less decline in FEV1 over 3 years among adults with CF http://ow.ly/yk6930ivCV8

Background: Significant resource constraints and critical care training gaps are responsible for the limited development of intensive care units (ICUs) in resource limited settings. We describe the implementation of an ICU in Haiti and report the successes and difficulties encountered throughout the process. We present a consecutive case series investigating an anesthesiologist, emergency, and critical care physician implemented endotracheal intubation and mechanical ventilation protocol in an austere environment with the assistance of telemedicine. Methods: A consecutive case series of fifteen patients admitted to an ICU at St. Luc Hospital located in Portau-Prince, Haiti, between the months of February 2012 to April 2014 is reported. Causes of respiratory failure and the clinical course are presented. Patients were followed to either death or discharge. Results: Fifteen patients (eight women and seven men) were included in the study with an average age of 37.7 years. The mean duration of ventilation was three days. Of the fifteen patients intubated, five patients (33.3%) survived and were discharged from the ICU. Of the five surviving patients, two were intubated for status epilepticus, one for status asthmaticus and one for hyperosmolar coma associated with intracerebral hemorrhage. Of the patients dying on the ventilator, four patients died from pneumonia, two from renal failure, and one from tetanus. The remaining three died from strokes and cardiac arrests. Conclusions: Mortality of mechanically ventilated patients in a resource-limited country is significant. Focused training in core critical care skills aimed at increasing the endotracheal intubation and ventilatory management capacity of local medical staff should be a priority in order to continue to develop ICUs in these austere environments. Collaborative educational and training efforts directed by anesthesiologists, emergency, and critical care physicians, and aided by telemedicine can facilitate realizing this goal.

Background G551D is a class III mutation of the cystic fibrosis transmembrane regulator (CFTR) that results in impaired chloride channel function in cystic fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride, weight, lung function, and pulmonary exacerbation rate in CF patients with G551D mutations, but its effect on the airway microbiome remains poorly characterised. Methods Twenty CF patients with at least one G551D mutation from a single centre were recruited to a 4month double-blind, placebo-controlled, crossover study of ivacaftor with 28days of active treatment. Sputum microbiota composition was assessed by 16S rRNA gene amplicon sequencing and quantitative PCR at five key time points, along with regular clinical review, respiratory function assessment, and peripheral blood testing. Results No significant difference in microbiota composition was observed in subjects following ivacaftor treatment or placebo (PERMANOVA P = 0.95, square root ECV=−4.94, 9479 permutations). Microbiota composition variance was significantly greater between subjects, than within subjects over time ( P U test), and an additional within-patient paired assessment of microbiota similarity was therefore performed. Again, change in microbiota composition was not significantly greater during treatment with ivacaftor compared to placebo (Wilcoxon test, P =0.51). A significant change in microbiota composition was however associated with any change in antibiotic exposure, regardless of whether ivacaftor or placebo was administered ( P =0.006). In a small, subgroup analysis of subjects whose antibiotic exposure did not change within the study period, a significant reduction in total bacterial load was observed during treatment with ivacaftor ( P =0.004, two-tailed paired Student's t- test). Conclusions The short-term impact of ivacaftor therapy on sputum microbiota composition in patients with G551D mutations are modest compared to those resulting from antibiotic exposure, and may be masked by changes in antibiotic treatment regimen.

Background: While CD19 chimeric antigen receptor T cell therapy (CAR-T) therapy does not use myeloablative chemotherapy, patients with aggressive lymphoma treated with CAR-T are immunosuppressed from lymphodepletion chemotherapy, and prolonged B cell aplasia and hypogammaglobulinemia from CAR-T. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) has not been formally studied. We report the vaccine titers of patients treated with CAR-T at Mayo Clinic, Rochester. Methods: We conducted a retrospective chart review of patients who received CAR-T from 9/2018 to 4/2021 for treatment of aggressive lymphoma at Mayo Clinic, Rochester. Data was collected on anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 post CAR-T. Clinical assays for vaccine titers were used for patient assessment and threshold for clinical assays was used to define antibody titer as positive or negative. Results: In our cohort of 87 CAR-T patients, 83 (94%) patients were infused with axicabtagene ciloleucel, 4 (5%) patients received brexucabtagene autoleucel and 1 (1%) received tisagenlecleucel. Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Streptococcus pneumoniae (Strep PNA). Similar trends were seen whether patients had autologous stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table 1). At 3 months post CAR-T, overall seropositivity rates were similar when compared to pre-CAR-T levels for the prior transplant and no prior transplant group. For patients who had received intravenous immunoglobulin (IVIG) supplement prophylactically (for IVIG For patients who did not receive IVIG prophylaxis after CAR-T, seropositivity rate for hepatitis A and B was low. In addition, some of these patients had a loss of seropositivity for Strep PNA (2/5, 40%) and hepatitis A (1/4, 25%). Conclusion: The presence of protective vaccine titers is variable for patients receiving CAR-T therapy, regardless of recent ASCT. The loss of protective titers post CAR-T was low. The need for immunization post CAR-T may remain important regardless of transplant status prior to CAR-T. Prophylactic IVIG does not confer complete immunization protection. Optimal timing for immunization post CAR-T is probably unknown and may need to be considered earlier for patients not on prophylactic IVIG. Further study with longer follow-up is needed to inform the need for immunization and optimal timing post CAR-T. Figure 1 Figure 1. Disclosures Bennani: Kymera: Other: Advisory Board; Vividion: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board. Paludo: Karyopharm: Research Funding. Wang: LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; Genentech: Research Funding; Novartis: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; InnoCare: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Lin: Sorrento: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Vineti: Consultancy; Juno: Consultancy; Legend: Consultancy; Gamida Cell: Consultancy; Merck: Research Funding; Bluebird Bio: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Background:Previous research regarding anxiety as a predictor of future cognitive decline in older adults is limited and inconsistent. We examined the independent relationship between anxiety symptoms and subsequent cognitive decline.Methods:We included 2,818 community-dwelling older men (mean age = 76.1, SD ±5.3 years) who were followed on an average for 3.4 years. We assessed anxiety symptoms at baseline using the Goldberg Anxiety Scale (GAS; range = 0–9). We assessed cognitive function at baseline and at two subsequent visits using the Modified Mini-Mental State Examination (3MS; global cognition) and the Trails B test (executive function).Results:At baseline, there were 690 (24%) men with mild anxiety symptoms (GAS 1–4) and 226 (8%) men with moderate/severe symptoms (GAS 5–9). Men with anxiety symptoms were more likely to have depressed mood, poor sleep, more chronic medical conditions, and more impairment in activities of daily living compared to those with no anxiety symptoms. Compared to those with no anxiety symptoms at baseline, men with any anxiety symptoms were more likely to have substantial worsening in Trails B completion time (OR = 1.56, 95% CI 1.19, 2.05). The association was attenuated after adjusting for potential confounders, including depression and poor sleep, but remained significant (OR = 1.40, 95% CI 1.04, 1.88).Conclusion:In cognitively healthy older men, mild anxiety symptoms may potentially predict future decline in executive functioning. Anxiety is likely a manifestation of an underlying neurodegenerative process rather than a cause.

OBJECTIVES: Research is limited and findings conflict regarding anxiety as a predictor of future cognitive decline in the oldest old persons. We examined the relationship between levels of and changes in anxiety symptoms, and subsequent dementia and mild cognitive impairment (MCI) in the oldest old women. METHOD: We conducted secondary analyses of data collected from 1,425 community-dwelling women (mean age = 82.8, SD ±3.1 years) followed on average for five years. The Goldberg Anxiety Scale was used to assess anxiety symptoms at baseline, and an expert clinical panel adjudicated dementia and MCI at follow-up. Participants with probable cognitive impairment (Mini-Mental State Examination score

ORKAMBI (ivacaftor-lumacaftor [LUMA]) and KALYDECO (ivacaftor; IVA) are two new breakthrough cystic fibrosis (CF) drugs that directly modulate the activity and trafficking of the defective CFTR underlying the CF disease state. Currently, no therapeutic drug monitoring assays exist for these very expensive, albeit, important drugs. In this study, for the first time HPLC and LC-MS methods were developed and validated for rapid detection and quantification of IVA and its major metabolites hydroxymethyl-IVA M1 (active) and IVA-carboxylate M6 (inactive); and LUMA in the plasma and sputum of CF patients. With a mobile phase consisting of acetonitrile/water:0.1% formic acid (60:40 v/v) at a flow rate of 1 mL/min, a linear correlation was observed over a concentration range from 0.01 to 10 μg/mL in human plasma (IVA R2>0.999, IVA M1 R2> 0.9961, IVA M6 R2>0.9898, LUMA R2>0.9954). The assay was successfully utilized to quantify the concentration of LUMA, IVA, M1 and M6 in the plasma and sputum of CF patients undergoing therapy with KALYDECO (IVA 150 mg/q12 h) or ORKAMBI (200 mg/q12 h LUMA-125 mg/q12 h IVA). The KALYDECO patient exhibited an IVA plasma concentration of 0.97 μg/mL at 2.5 h post dosage. M1 and M6 plasma concentrations were 0.50 μg/mL and 0.16 μg/mL, respectively. Surprisingly, the ORKAMBI patient displayed very low plasma concentrations of IVA (0.06 μg/mL) and M1 (0.07 μg/mL). The M6 concentrations (0.15 μg/mL) were comparable to those of the KALYDECO patient. However, we observed a relatively high plasma concentration of LUMA (4.42 μg/mL). This reliable and novel method offers a simple and sensitive approach for therapeutic drug monitoring of KALYDECO and ORKAMBI in plasma and sputum. The introduction of the assay into the clinical setting will facilitate pharmacokinetics/pharmacodynamic analysis and assist clinicians to develop more cost effective and efficacious dosage regimens for these breakthrough CF drugs.

Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor recently approved for the treatment of a variety of B-cell malignancies [1,2]. BTK inhibitors were not anticipated to cause invasive fungal i...

Background Several disasters over the past decade have highlighted the need for strong acute-care systems in Haiti. As part of a multifaceted approach to improving national acute-care training, the Research and Education consortium for Acute Care in Haiti (REACH) launched the inaugural Haiti Acute and Emergency Care Conference (HAECC). # Methods REACH is a Haitian-led, multinational collaboration based out of Saint Luc Hospital in Port-au-Prince. The first HAECC was held in April, 2017. Pre- and post-course evaluation consisted of subjective and objective components. Differences between pre- and post-responses were determined using McNemar's test of paired proportions. # Results 57 participants from 21 hospitals in five Haitian departments were included. The majority (37/58, 63.8%) were physicians. Most (33/57, 57.9%) had no prior training in acute or emergency care, but 8/57 (14.0%) had taken ATLS/ACLS, 11/57 (19.3%) had taken a formal course not internationally recognized, and only 1/57 (1.8%) had completed acute care specialty training. 43.7% (25/57) reported routine access to point-of-care ultrasound. Following course completion, participants felt significantly more comfortable managing basic emergency conditions (up to 25/57, 43.9% increase, *P*\

The space radiation environment is a complex mixture of particle types and energies originating from sources inside and outside of the galaxy. These environments may be modified by the heliospheric and geomagnetic conditions as well as planetary bodies and vehicle or habitat mass shielding. In low Earth orbit (LEO), the geomagnetic field deflects a portion of the galactic cosmic rays (GCR) and all but the most intense solar particle events (SPE). There are also dynamic belts of trapped electrons and protons with low to medium energy and intense particle count rates. In deep space, the GCR exposure is more severe than in LEO and varies inversely with solar activity. Unpredictable solar storms also present an acute risk to astronauts if adequate shielding is not provided. Near planetary surfaces such as the Earth, moon or Mars, secondary particles are produced when the ambient deep space radiation environment interacts with these surfaces and/or atmospheres. These secondary particles further complicate the local radiation environment and modify the associated health risks. Characterizing the radiation fields in this vast array of scenarios and environments is a challenging task and is currently accomplished with a combination of computational models and dosimetry. The computational tools include models for the ambient space radiation environment, mass shielding geometry, and atomic and nuclear interaction parameters. These models are then coupled to a radiation transport code to describe the radiation field at the location of interest within a vehicle or habitat. Many new advances in these models have been made in the last decade, and the present review article focuses on the progress and contributions made by workers and collaborators at NASA Langley Research Center in the same time frame. Although great progress has been made, and models continue to improve, significant gaps remain and are discussed in the context of planned future missions. Of particular interest is the juxtaposition of various review committee findings regarding the accuracy and gaps of combined space radiation environment, physics, and transport models with the progress achieved over the past decade. While current models are now fully capable of characterizing radiation environments in the broad range of forecasted mission scenarios, it should be remembered that uncertainties still remain and need to be addressed.

With only 9105 new US tuberculosis (TB) cases reported in 2017, expert consultation is essential for TB care. Data were captured 2013–2017 from consultations by 5 CDC-funded centers, now the TB Centers of Excellence (COEs). 14 586 consultations were provided to TB providers, most related to TB disease and treatment regimens.

7555 Background: While CAR-T therapy is not myelo-ablative, patients with aggressive lymphoma treated with CD19 chimeric antigen receptor T cell therapy (CAR-T) are lymphodepleted and have prolonged B cell aplasia. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) is not known. We report the vaccine titers of patients treated with axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Methods: Retrospective chart review of adult lymphoma patients who received axi-cel from 9/2018 to 9/2020 for anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 (MO3) post CAR-T. Results: Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Strep pneumoniae (Strep PNA) (Table). Similar trends were seen whether patients had stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table). Compared to patients who had ASCT, those who did not had higher rate of positive titer for Strep PNA and lower rate for hepatitis B, Mumps, and VZV. The same trend for sero-positive rate were observed at MO3 post CAR-T. Patients with IgG

Ecologists and conservation biologists conducting long-term research programs in the tropics must confront serious ethical challenges that revolve around economic inequalities, cultural differences, supporting the local communities as much as possible, and sharing the knowledge produced by the research. In this collective article, researchers share their experiences and perspectives in dealing with the ethical issues that arise during research activities and cannot be ignored.

Increasing numbers of international patients are receiving care at US medical centers, entailing various challenges and benefits to all involved. Despite the potential challenges, the collective experiences can transform healthcare providers and their institutions into better physicians, better medical centers, and overall better members of a global society with increased awareness of the global human experience.

Background: Tublosis (TB) and the approaches to successful management are commonly misunderstood health topics among patients and family members within resource-limited settings. Such public misconceptions often result in delayed diagnoses of afflicted patients, suboptimal compliance with prescribed therapies and a negative community social stigma that hinders effective contact investigations. Objective: To determine through an observational field pilot study if videography-based TB education program can be implemented in busy resource-limited outpatient TB clinic settings and improve both patient and family understanding of TB and its treatment, as well as, improve the efficiency of TB medical evaluations and corresponding contact investigations. Methods: We produced and implemented a videography-based health educational pilot strategy in 14 TB clinics within El Salvador to supplement the discussions between health providers, patients and families. Field observations and impressions after the first year of implementation were recorded. Results: After viewing the video, patient impressions revealed greater understanding of TB including how it's transmitted and successfully treated, as well as, a more optimistic outlook of the diagnosis. Family members viewing the video displayed less fear and greater interest in TB and also exhibited more support for relatives undergoing evaluation or treatment. Salvadorian TB health providers reported improvements in patient compliance with treatment, contact investigations of suspected patients, delivery of sputum samples for testing, clinic time-efficiency spent with patients, and an observed reduction of negative family stigma of TB. Conclusions: Our findings suggest that videography-based TB education can be successfully implemented in busy and resource-limited outpatient settings, and can provide a potentially efficient and low-cost effective strategy towards optimizing patient understanding, acceptance and compliance with TB treatment recommendations. This feasibility pilot study provides an opportunity within underresourced clinics for further evaluation regarding the favorable educational and sustainable impact of videography-based health education. Keywords: Tuberculosis, Videography, Education, El Salvador, Communication

Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed.

A computationally efficient 3DHZETRN code with enhanced neutron and light ion (Z ≤ 2) propagation was recently developed for complex, inhomogeneous shield geometry described by combinatorial objects. Comparisons were made between 3DHZETRN results and Monte Carlo (MC) simulations at locations within the combinatorial geometry, and it was shown that 3DHZETRN agrees with the MC codes to the extent they agree with each other. In the present report, the 3DHZETRN code is extended to enable analysis in ray-trace geometry. This latest extension enables the code to be used within current engineering design practices utilizing fully detailed vehicle and habitat geometries. Through convergence testing, it is shown that fidelity in an actual shield geometry can be maintained in the discrete ray-trace description by systematically increasing the number of discrete rays used. It is also shown that this fidelity is carried into transport procedures and resulting exposure quantities without sacrificing computational efficiency.

Background The current health system in Australia is comprised of both electronic- and paper-based medical records. The Federal Government has approved funding for the development of an individual health identifier and a universally adopted online health repository. Aims To determine attitudes and beliefs of patients and healthcare workers regarding the use of stored medical information and the personally controlled electronic health record (PCEHR) in selected major hospitals in Victoria. Methods Qualitative survey of patients and healthcare workers (n = 600 each group) conducted during 2014 across five major hospitals in Melbourne to measure the awareness, attitudes and barriers to electronic health and the PCEHR. Results Of the patients, 93.3% support the concept of a shared electronic healthcare record, 33.7% were aware of the PCEHR and only 11% had registered. The majority of healthcare workers believed that the presence of a shared health record would result in an increased appropriateness of care and patient safety by reducing adverse drug events and improving the timeliness of care provided. However, only 46% of healthcare workers were aware of the PCEHR. Conclusions This study provides a baseline evaluation of perceptions surrounding eHealth and PCHER in acute health services in five metropolitan centres. While there appears to be a readiness for adoption of these strategies for healthcare documentation, patients require motivation to register for the PCEHR, and healthcare workers require more information on the potential benefits to them to achieve more timely and efficient care.

Extensively drug-resistant (XDR) tuberculosis (TB) is an unfortunate by-product of mankind's medical and pharmaceutical ingenuity during the past 60 years. Although new drug developments have enabled TB to be more readily curable, inappropriate TB management has led to the emergence of drug-resistant disease. Extensively drug-resistant TB describes Mycobacterium tuberculosis that is collectively resistant to isoniazid, rifampin, a fluoroquinolone, and an injectable agent. It proliferates when established case management and infection control procedures are not followed. Optimized treatment outcomes necessitate time-sensitive diagnoses, along with expanded combinations and prolonged durations of antimicrobial drug therapy. The challenges to public health institutions are immense and most noteworthy in underresourced communities and in patients coinfected with human immunodeficiency virus. A comprehensive and multidisciplinary case management approach is required to optimize outcomes. We review the principles of TB drug resistance and the risk factors, diagnosis, and managerial approaches for extensively drug-resistant TB. Treatment outcomes, cost, and unresolved medical issues are also discussed.

Supportive care guidelines recommend antimold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed to have high risk for invasive fungal infection, leading to long-term use of voriconazole after allogeneic HSCT in patients who remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients after solid organ transplantation, HSCT, and leukemia therapy. The aims of this study were to describe the frequency and clinical presentation of patients presenting with pain and fluoride excess among allogeneic HSCT patients taking voriconazole, to identify when a plasma fluoride concentration was measured with respect to voriconazole initiation and onset of pain, and to describe the outcomes of patients with fluoride excess in the setting of HSCT. A retrospective review was conducted of all adult allogeneic HSCT patients receiving voriconazole at Mayo Clinic in Rochester, Minnesota, between January 1, 2009 and July 31, 2012. Of 242 patients included, 32 had plasma fluoride measured to explore the etiology of musculoskeletal pain. In 31 patients with fluoride measurement while on voriconazole, 29 (93.5%) had elevated levels. The median plasma fluoride was 11.1 μmol/L (range, 2.4 to 24.7). The median duration of voriconazole was 163 days (range, 2 to 1327). The median time to fluoride measurement was 128 days after voriconazole initiation (range, 28 to 692). At 1 year after the start of voriconazole after HSCT, 15.3% of patients had developed pain associated with voriconazole use and 35.7% developed pain while on voriconazole after 2 years. Of the patients with an elevated fluoride level, 22 discontinued voriconazole; pain resolved or improved in 15, stabilized in 3, and worsened in 4 patients. Ten patients continued voriconazole; pain resolved or improved in 7, was attributable to alternative causes in 2, and undefined in 1. Serum creatinine, estimated glomerular filtration rate, alkaline phosphatase, and voriconazole concentration did not predict for fluoride excess and associated pain. Periostitis due to fluoride excess is a common adverse effect of voriconazole that should be considered in patients presenting with pain and is often reversible after drug discontinuation. Alternative antifungal agents with a lower risk for fluoride excess should be considered in patients receiving voriconazole who develop fluoride excess and pain.

In comparison to the mainland, populations of rodents on islands are often characterized by a suite of life history characteristics termed the “island syndrome.” Populations of rodents introduced to islands are also well known for their impacts on native species that have evolved in the absence of mammalian predators. We studied the ecology and behavior of introduced house mice Mus musculus on Gough Island where they are the only terrestrial mammal and where their predatory behavior is having a devastating impact on the island’s burrowing petrel (order Procellariiformes ) population and the Critically Endangered Tristan albatross Diomedea dabbenena . Mice on Gough exhibit extreme features of the island syndrome, including: a body mass 50–60% greater than any other island mouse population, peak densities among the highest recorded for island populations, and low seasonal variation in numbers compared to other studied islands. Seasonal patterns of breeding and survival were linked to body condition and mass, and mice in areas with high chick predation rates were able to maintain higher mass and condition during the winter when mouse mortality rates peak. Within-site patterns of chick predation indicate that proximity to neighboring predated nests and nesting densities are important factors in determining the likelihood of predation. We conclude that selection for extreme body mass and predatory behavior of mice result from enhanced overwinter survival. Small mammal populations at temperate and high latitudes are normally limited by high mortality during the winter, but on Gough Island mice avoid that by exploiting the island’s abundant seabird chicks.