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IMPORTANCE: There are consistent data demonstrating that socioeconomic disadvantage is associated with risk of premature mortality, but research on the relationship between neighborhood socioeconomic factors and premature mortality is limited. Most studies evaluating the association between neighborhood socioeconomic status (SES) and mortality have used a single assessment of SES during middle to older adulthood, thereby not considering the contribution of early life neighborhood SES. OBJECTIVE: To investigate the association of life course neighborhood SES and premature mortality. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included Black and White participants of the multicenter Atherosclerosis Risk in Communities Study, a multicenter study conducted in 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the northwestern suburbs of Minneapolis, Minnesota. Participants were followed up for a mean (SD) of 18.8 (5.7) years (1996-2020). Statistical analysis was performed from March 2023 through May 2024. EXPOSURE: Participants residential addresses during childhood, young adulthood, and middle adulthood were linked with US Census-based socioeconomic indicators to create summary neighborhood SES scores for each of these life epochs. Neighborhood SES scores were categorized into distribution-based tertiles. MAIN OUTCOMES AND MEASURES: Premature death was defined as all-cause mortality occurring before age 75 years. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Among 12 610 study participants, the mean (SD) age at baseline was 62.6 (5.6) years; 3181 (25.2%) were Black and 9429 (74.8%) were White; and 7222 (57.3%) were women. The lowest, compared with the highest tertile, of neighborhood SES score in middle adulthood was associated with higher risk of premature mortality (HR, 1.28; 95% CI, 1.07-1.54). Similar associations were observed for neighborhood SES in young adulthood among women (HR, 1.25; 95% CI, 1.00-1.56) and neighborhood SES in childhood among White participants (HR, 1.25; 95% CI, 1.01-1.56). Participants whose neighborhood SES remained low from young to middle adulthood had an increased premature mortality risk compared with those whose neighborhood SES remained high (HR, 1.25; 95% CI, 1.05-1.49). CONCLUSIONS AND RELEVANCE: In this study, low neighborhood SES was associated with premature mortality. The risk of premature mortality was greatest among individuals experiencing persistently low neighborhood SES from young to middle adulthood. Place-based interventions that target neighborhood social determinants of health should be designed from a life course perspective that accounts for early-life socioeconomic inequality.

BACKGROUND: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. METHODS: We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. RESULTS: All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL

An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.

BACKGROUND: Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex. METHODS: We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019. We identified all individuals with a diagnosis of anal intraepithelial neoplasia grade III and determined their HIV status. We estimated the average annual percentage change of anal intraepithelial neoplasia grade III using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of squamous cell carcinoma of the anus following an anal intraepithelial neoplasia grade III diagnosis stratified by sex, HIV status, and prior AIDS diagnosis. RESULTS: Among people with HIV, average annual percentage changes for anal intraepithelial neoplasia grade III were 15% (95% confidence interval [CI] = 12% to 17%) per year among females and 12% (95% CI = 11% to 14%) among males. Average annual percentage changes for those without HIV were 8% (95% CI = 7% to 8%) for females and 8% (95% CI = 6% to 9%) for males. Among people with HIV, a prior AIDS diagnosis was associated with a 2.7-fold (95% CI = 2.23 to 3.40) and 1.9-fold (95% CI = 1.72 to 2.02) increased risk of anal intraepithelial neoplasia grade III diagnosis for females and males, respectively. Five-year cumulative incidence of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III for people with HIV with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively. CONCLUSIONS: Rates of anal intraepithelial neoplasia grade III diagnoses have increased since 1996, particularly for people with HIV, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of anal intraepithelial neoplasia grade III diagnosis.

Beavers serve critical ecological functions and play the role of keystone species in wetland ecosystems. Yet, their ecological engineering can sometimes cause flooding or other damage to human infrastructure and agriculture necessitating management action. In an effort to preserve the ecological benefits of beavers while mitigating damages, many stakeholders increasingly seek non-lethal solutions that are part of the USDA Wildlife Services (WS) Integrated Wildlife Damage Management approach. Research at the Wildlife Services National Wildlife Research Center aims to expand this portfolio by investigating drivers of beaver damage and developing, evaluating, and refining effective tools for non-lethal beaver management. In this paper we provide an overview of non-lethal beaver management tools showing promise in field operations, including: 1) physically excluding beaver from key areas; 2) managing water flow around beaver impoundments; 3) translocating beaver colonies from damaging to desired areas; 4) novel developments such as eDNA, drone surveys, and fertility control. We hope to generate discussions in the wildlife damage management community to better understand needs and knowledge gaps requiring additional research effort.

Roof rats (Rattus rattus) are an invasive rodent that can cause substantial damage in citrus orchards. Their populations appear to be expanding throughout California, yet little is known about efficacious, cost-effective strategies to manage this invasive pest while minimizing pesticide use. Therefore, we developed two Integrated Pest Management (IPM) programs based on results of recent studies that incorporated observations of roof rat movement patterns, compared monitoring tools, and tested trapping and baiting options. Both IPM programs utilized elevated bait stations containing 0.005% diphacinone-treated oats and trapping, and we compared those programs to a bait-station only approach to determine which strategies were most practical. Initial IPM plots included a combination of elevated bait stations followed by a brief snap-trapping program and a longer-duration trapping program with Goodnature® A24 traps to hopefully keep rat numbers at low levels (Trial 1). Although initial bait applications were effective at reducing rat numbers, populations quickly rebounded within both the bait station only and IPM treatment areas within two-months following the completion of the baiting programs. Additionally, costs for this initial IPM approach were almost five times as much as a bait station approach. Our second IPM strategy (Trial 2) again incorporated an initial bait application period to knock down roof rat populations, followed by the use of trapping tunnels that contained two snap traps to further reduce/maintain rat numbers longer-term. We again observed effective knockdown with bait applications. However, in contrast to Trial 1, we observed substantial success with trapping tunnels at maintaining, and even increasing, overall efficacy within IPM plots, and IPM plots were always more efficacious than bait station only plots. Although the bait station only approach was less costly than the IPM approach used in Trial 2, the cost disparity was substantially less than that for Trial 1, and the cost difference disappeared during subsequent years, indicating long-term cost-effectiveness of this IPM approach. Collectively, the relatively low cost and high efficacy of a management program that incorporates initial bait applications to knock down roof rat populations, followed by a long-term snap-trapping program to maintain low densities, should provide an effective strategy for managing roof rats in citrus orchards.

House mice and rats have been introduced to most countries and islands worldwide and represent serious threats to biodiversity, economic enterprise, and human health. Genome editing and gene drives are being explored as new genetic biocontrol methods to effectively suppress rodent pests. An essential step in the translation of this technology to field-ready tools is to administer breeding and behavioral trials with freely-interacting genetically modified (GM) rodents. Due to the potential impacts of unintended release of GM organisms, these trials will require biosecure animal facilities that are rigorously tested to ensure physical containment. This study was conducted to develop and evaluate the biosecurity of a physical containment facility for house mouse trials at USDA’s National Wildlife Research Center. First, we conducted >20 trials with 75 wild-caught (non-GM) house mice to test their ability to escape from small containment units (0.35 m2). During these trials that lasted >160 days, mouse behaviors and escape attempts were documented following exposure to attractants (high value foods and potential mates) as motivators for escape. Just two mice success­fully breached containment during early trials, and both were from chewing small holes in plastic walls that allowed escape to the other side of the containment unit. In a second series of trials, we assessed containment efficacy in a large (24 m2) arena intended to more closely replicate conditions of free-breeding wild mice. In these trials, mice were held in groups of six to 26 for up to 6 months. Across trials, only one mouse escaped the arena, an incident most likely attributable to human error during routine animal husbandry activities. This mouse was captured in the secondary containment (live-trap) within hours of breaching the primary containment. Overall, the containment strategy utilized here presents a robust design, with redundant containment mechanisms that should serve as a model for future behavioral trials using GM rodents. Additionally, our study highlights the need for rigorous staff training, careful attention to construction methods and materials, and adhering to biosecurity protocols to ensure the highest levels of containment that will be essential for testing efficacy of genetic biocontrols.

The eradication of black rats from Dry Tortugas National Park (DRTO; 42 ha land mass) was completed in January 2022 through collaboration between USDA APHIS Wildlife Services and the National Park Service. Black rats had been documented throughout DRTO since the park was established in 1935. Rat predation of ground nesting birds at DRTO has included brown noddies and sooty terns. Additionally, black rats have damaged equipment and infrastructure throughout the park, and caused human health and safety issues in staff residences. For this eradication, WS chose to use a diphacinone-based rodenticide: Diphacinone-50 Conservation. Diphacinone was chosen instead of brodifacoum because it poses lower risks to non-target species (e.g., 100× less toxic to birds) and has less environmental accumulation over time. Diphacinone-50 Conservation was deployed throughout the park in bait stations placed on a 30m × 30m grid. Bait stations were baited and monitored daily for 14 days. Additionally, three hand broadcast applications were utilized during the eradication in areas of the park closed to visitors. Daily monitoring of the bait stations showed a high initial uptake of the toxicant. Also, monitoring using thermal imaging optics was used throughout the eradication to surveil bait uptake and rat activity. No rats were detected during the last four days of the eradication. Post-eradication monitoring was conducted quarterly for the first year following the eradication, and twice during the second year. Post eradication monitoring consisted of 120 snap traps and chew sachets placed throughout the park for four nights. In addition, track surveys were completed along the dune lines and thermal monitoring was conducted after dark during each monitoring period. The eradication was deemed a success in January 2024. National Park Service currently maintains a strict biosecurity plan for DRTO. This plan includes permanent bait stations and cameras placed in areas of likely reintroductions, monitoring of docking vessels, and checking cargo before distribution. Two weeks post eradication, NPS personnel observed a rat jump off a vessel onto DRTO. This rat was later found dead after consuming toxicant from the permanent bait stations. No rats have been detected at DRTO since.

Invasive house mice threaten native biodiversity on many of the world’s islands. Best practice for eradicating house mouse populations from islands currently relies on bait containing the anticoagulant rodenticide brodifacoum. These baits are typically either broadcast (by hand or by helicopter in natural areas) or placed in bait stations (in human infrastructure or in areas where open broadcast is not permitted). There have been many successful mouse eradications using these methods, including 29 of 36 attempts of islands being successful (81%) in New Zealand. Following recent failed mouse eradications on Gough Island (South Atlantic, 2021) and Midway Atoll (North Pacific, 2023), a workshop was convened with 24 people attending (16 in-person, 8 on-line) from 7 countries (Australia, Canada, France, NZ, South Africa, UK, US), to discuss some hypotheses for what may have contributed to these unsuccessful outcomes. The workshop was held in Palmerston North, New Zealand, between November 27 and 29, 2023. Discussions over the three days revolved around three hypotheses. We present the key factors hypothesized for why eradications failed on these two islands. We also outline research and operational needs that were identified in the workshop that can contribute to improved outcomes for future eradications of house mice from targeted islands.

Use of a contraceptive (i.e., fertility control) is attractive for rodent management where lethal control is unwanted. Although population reduction is generally unachievable with small-scale, short-term contraceptive use, reduced juvenile recruitment is achievable. The injectable immunocontraceptive vaccine GonaCon (active ingredient: gonadotropin releasing hormone [GnRH]) was registered in 2022 by the U.S. EPA for controlling fertility of female prairie dogs (Cynomys, a type of ground squirrel) in urban/suburban settings. Here we: 1) describe past research, including a replicated field study in Colorado (GonaCon treatment vs. control sites) testing efficacy of GonaCon in prairie dogs, which gave rise to the EPA registration of this product, 2) outline future research needs for prairie dog population management with GonaCon–Prairie Dogs, 3) describe the steps required to possibly register GonaCon for additional rodent species, and 4) describe the other fertility control pesticide products that are currently registered for use against rodents in the U.S. During the replicated field study in Colorado, prairie dogs were live-trapped in a portion (avg: 18.5%, range: 7-37%) of each colony’s total area. In treatment plots, every female captured ≥ 660 g was injected with 0.4 ml of GonaCon. GonaCon was highly effective in controlling female fertility during the first year (2019), as juvenile density was reduced 3×, but not in the second year (2020) following treatment. Treating whole colonies of prairie dogs is favored, yet if small or partial colony treatment is desired then annual GonaCon treatment may be needed. An amendment to the EPA label is in progress to allow treatment of both male and female prairie dogs. Due to recent interest from land and pest managers, other fertility control products and the steps required to possibly get GonaCon registered for additional rodent species are also outlined.

Treatment of screen-detected anal high-grade squamous intraepithelial lesions has been shown to effectively reduce the incidence of invasive anal cancer in people with HIV. We provide population-based estimates of cumulative incidence of anal cancer by risk group and age at HIV or AIDS diagnosis. The 0- to 10-year cumulative incidence of anal cancer for men who have sex with men and are younger than 30 years of age at HIV diagnosis was 0.17% (95% confidence interval [CI] = 0.13% to 0.20%) compared with 0.04% (95% CI = 0.02% to 0.06%) in other men and 0.03% (95% CI = 0.01% to 0.04%) in women. For men who have sex with men and have a diagnosis of AIDS and are younger than 30 years of age, the 0- to 10-year cumulative incidence was 0.35% (95% CI = 0.28% to 0.41%). Among people with HIV, men who have sex with men are at the greatest risk of anal cancer, and those with a diagnosis of AIDS had higher risk than those without AIDS. These estimates may inform recommendations for priority populations that could benefit most from anal cancer screening and treatment.

BackgroundIntramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables.ObjectiveTo examine LA-ART in a population of PWH that includes those with viremia.DesignObservational cohort study.SettingUrban academic safety-net HIV clinic.PatientsPublicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use.InterventionDemonstration project of long-acting injectable CAB-RPV.MeasurementsDescriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data.ResultsBetween June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks.LimitationSingle-site study.ConclusionThis project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed.Primary funding sourceNational Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.

BackgroundLong-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naive or experienced people with human immunodeficiency virus (HIV; PWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART.MethodsWard 86 is a large HIV clinic in San Francisco that serves publicly insured and underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method.ResultsBetween June 2021 and April 2022, 51 patients initiated LAI-ART, with 39 receiving at least 2 follow-up injections by database closure (median age, 46 years; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients who initiated injections with viral suppression (median CD4 cell count, 706 cells/mm3), 100% (95% confidence interval [CI], 86%-100%) maintained viral suppression. Of 15 patients who initiated injections with detectable viremia (median CD4 cell count, 99 cells/mm3; mean log10 viral load, 4.67; standard deviation, 1.16), 12 (80%; 95% CI, 55%-93%) achieved viral suppression, and the other 3 had a 2-log viral load decline by a median of 22 days.ConclusionsThis small demonstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.

The combined burden of geriatric conditions, comorbidities, and HIV requires a model of HIV care that offers a comprehensive clinical approach with people 50 years or older with HIV. Golden Compass is an outpatient, multidisciplinary HIV-geriatrics program with an onsite HIV geriatrician, cardiologist, pharmacist, and social worker, offering specialist referrals, care navigation, and classes on improving functional status and cognition. Participants (13 patients and 11 primary care providers) were recruited using a non-probability sampling method to participate in semi-structured interviews on the perceived impact of Golden Compass on care delivered to older people with HIV. Interviews were transcribed verbatim and framework analysis used to analyze the transcripts. The perceived impacts of Golden Compass by patients and providers were organized by the Compass points (Northern: Heart and Mind, Eastern: Bones and Strength, Southern: Navigation and Network, Western: Dental, Hearing, and Vision). Overall, patients valued the focus on functional health and whole-person care, leading to greater trust in the ability of providers. Providers gained new skills through the geriatrics, cardiology and/or pharmacist consultations. The HIV-geriatrics specialty approach of Golden Compass improved functional ability and quality of life for older adults with HIV. Few integrated care programs for older people with HIV have been evaluated. This study adds to the limited literature demonstrating high patient and provider satisfaction with a HIV-care model that incorporated principles of geriatric medicine emphasizing a comprehensive approach to sustaining functional ability and improving quality of life.

Prairie dogs are an accessible and enjoyed wildlife species in Colorado that require occasional surveys because populations can change abruptly due to plague outbreaks or human-induced control. We evaluated the use of small copter drones at four prairie dog colonies on Open Space and Mountain Parks lands, City of Boulder, to determine if this methodology improves efficiency over ground-based survey methods. We counted prairie dogs and burrows using two types of drones (DJI Matric 210 and Autel Evo II) at altitudes 100', 150', and 400' (burrows only). We recorded video and merged still images into orthomosaics prior to having USDA staff analyze this imagery. We then compared the drone imagery counts to those of our simultaneous ground-based counts of prairie dogs. We determined that 100' altitude mosaics produced using DJI Matric 210 drone were most accurate (closest to true, ground-based counts) for burrow abundance. We were not able to identify the best drone and altitude combination for drone-based prairie dog abundance. Overall video and mosaics both had similar accuracy in most prairie dog counts, however 150' video was more accurate than 100' video. One staff member counted burrows more closely to true than did the other. Both staff members required about the same amount of time to count and analyze imagery; videos could be evaluated slightly faster than mosaics (average of 3.8 hours vs. 5.5 hours per imagery) when counting prairie dogs, and burrow counts (of mosaics) generally took 2-3 times longer to analyze (averaging 8.1 hours per imagery; range: 3-13 hours) than did prairie dog counts. The labor requirement of using drones for burrow and prairie dog counts is far more time consuming (3-4 times longer per hectare) than having field staff conduct the traditional on-the-ground counts that include repeated prairie dog counts in a day. Until drone technology improves to allow targeting larger colonies (>2 km2) and automated detection and counting of wildlife become more commonplace, drone surveys are unlikely to be a more efficient technique than ground-based surveys for evaluating prairie dog abundances.

The combined burden of geriatric conditions, comorbidities, and HIV requires a model of HIV care that offers a comprehensive clinical approach with people 50 years or older with HIV. Golden Compass is an outpatient, multidisciplinary HIV-geriatrics program with an onsite HIV geriatrician, cardiologist, pharmacist, and social worker, offering specialist referrals, care navigation, and classes on improving functional status and cognition. Participants (13 patients and 11 primary care providers) were recruited using a non-probability sampling method to participate in semi-structured interviews on the perceived impact of Golden Compass on care delivered to older people with HIV. Interviews were transcribed verbatim and framework analysis used to analyze the transcripts. The perceived impacts of Golden Compass by patients and providers were organized by the Compass points (Northern: Heart and Mind, Eastern: Bones and Strength, Southern: Navigation and Network, Western: Dental, Hearing, and Vision). Overall, patients valued the focus on functional health and whole-person care, leading to greater trust in the ability of providers. Providers gained new skills through the geriatrics, cardiology and/or pharmacist consultations. The HIV-geriatrics specialty approach of Golden Compass improved functional ability and quality of life for older adults with HIV. Few integrated care programs for older people with HIV have been evaluated. This study adds to the limited literature demonstrating high patient and provider satisfaction with a HIV-care model that incorporated principles of geriatric medicine emphasizing a comprehensive approach to sustaining functional ability and improving quality of life.

Asthma often worsens at night. To determine if the endogenous circadian system contributes to the nocturnal worsening of asthma, independent of sleep and other behavioral and environmental day/night cycles, we studied patients with asthma (without steroid use) over 3 wk in an ambulatory setting (with combined circadian, environmental, and behavioral effects) and across the circadian cycle in two complementary laboratory protocols performed in dim light, which separated circadian from environmental and behavioral effects: 1) a 38-h "constant routine," with continuous wakefulness, constant posture, 2-hourly isocaloric snacks, and 2) a 196-h "forced desynchrony" incorporating seven identical recurring 28-h sleep/wake cycles with all behaviors evenly scheduled across the circadian cycle. Indices of pulmonary function varied across the day in the ambulatory setting, and both laboratory protocols revealed significant circadian rhythms, with lowest function during the biological night, around 4:00 AM, uncovering a nocturnal exacerbation of asthma usually unnoticed or hidden by the presence of sleep. We also discovered a circadian rhythm in symptom-based rescue bronchodilator use (β2-adrenergic agonist inhaler) whereby inhaler use was four times more likely during the circadian night than day. There were additive influences on asthma from the circadian system plus sleep and other behavioral or environmental effects. Individuals with the lowest average pulmonary function tended to have the largest daily circadian variations and the largest behavioral cycle effects on asthma. When sleep was modeled to occur at night, the summed circadian, behavioral/environmental cycle effects almost perfectly matched the ambulatory data. Thus, the circadian system contributes to the common nocturnal worsening of asthma, implying that internal biological time should be considered for optimal therapy.

BackgroundStudies suggest lower risk of breast cancer in women with HIV versus without HIV. These estimates may be biased by lower life expectancy and younger age distribution of women with HIV. Our analysis evaluated this bias and characterized secular trends in breast cancer among women with HIV initiating antiretroviral therapy. We hypothesized breast cancer risk would increase over time as mortality decreased.SettingWomen with HIV prescribed antiretroviral therapy in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1997 through 2016.MethodsWe estimated breast cancer hazard (cause-specific hazard ratios) and cumulative incidence accounting for competing risks (subdistribution hazard ratios) to assess changes in breast cancer risk over time. This was assessed overall (1997-2016) and within/across calendar periods. Analyses were adjusted for race/ethnicity and inverse probability weighted for cohort. Cumulative incidence was graphically assessed by calendar period and race/ethnicity.ResultsWe observed 11,587 women during 1997-2016, contributing 63 incident breast cancer diagnoses and 1,353 deaths [73,445 person-years (median follow-up = 4.5 years)]. Breast cancer cumulative incidence was 3.2% for 1997-2016. We observed no secular trends in breast cancer hazard or cumulative incidence. There were annual declines in the hazard and cumulative incidence of death (cause-specific hazard ratios and subdistribution hazard ratios: 0.89, 95% confidence interval: 0.87 to 0.91) which remained within and across calendar periods.ConclusionsThese findings contradict the hypothesis of increasing breast cancer risk with declining mortality over time among women with HIV, suggesting limited impact of changing mortality on breast cancer risk. Additional inquiry is merited as survival improves among women with HIV.

Soluble adenylyl cyclase (sAC) is a HCO3 - -stimulated enzyme that produces the ubiquitous signalling molecule cAMP, and deemed an evolutionarily conserved acid-base sensor. However, its presence is not yet confirmed in bony fishes, the most abundant and diverse of vertebrates. Here, we identified sAC genes in various cartilaginous, ray-finned and lobe-finned fish species. Next, we focused on rainbow trout sAC (rtsAC) and identified 20 potential alternative spliced mRNAs coding for protein isoforms ranging in size from 28 to 186 kDa. Biochemical and kinetic analyses on purified recombinant rtsAC protein determined stimulation by HCO3 - at physiologically relevant levels for fish internal fluids (EC50 ∼ 7 mM). rtsAC activity was sensitive to KH7, LRE1, and DIDS (established inhibitors of sAC from other organisms), and insensitive to forskolin and 2,5-dideoxyadenosine (modulators of transmembrane adenylyl cyclases). Western blot and immunocytochemistry revealed high rtsAC expression in gill ion-transporting cells, hepatocytes, red blood cells, myocytes and cardiomyocytes. Analyses in the cell line RTgill-W1 suggested that some of the longer rtsAC isoforms may be preferentially localized in the nucleus, the Golgi apparatus and podosomes. These results indicate that sAC is poised to mediate multiple acid-base homeostatic responses in bony fishes, and provide cues about potential novel functions in mammals.

ObjectivesTo determine the incidence of clinically diagnosed depression and anxiety in adolescents with nonalcoholic fatty liver disease (NAFLD).MethodsThis was a prospective, longitudinal cohort study between January 1, 2012 and July 1, 2018 conducted in a Children's Hospital Pediatric Gastroenterology Clinic. Participants included adolescents 12 to 17 years old at baseline with biopsy-confirmed NAFLD. The primary outcomes were having depression and/or anxiety based upon a clinical diagnosis established by a physician or psychologist. The rates of depression and anxiety were measured at baseline and longitudinally throughout follow-up.ResultsA total of 160 adolescents with NAFLD were followed for a mean of 3.8 years. At baseline, 8.1% had a diagnosis of depression. During follow-up, an additional 9.5% (95% confidence interval, 4.7-14.3) developed depression. The incidence density of depression was 27 new cases per 1000 person-years at risk. In adolescents with NAFLD, 6.3% had anxiety at baseline and 6.7% (95% confidence interval, 2.6-10.7) developed anxiety during follow-up. The incidence density of anxiety was 18 new cases per 1000 person-years at risk. The change in alanine aminotransferase was significantly worse for adolescents with NAFLD who developed depression compared to those who did not develop depression (P

BackgroundSince the early 1980s, papillary thyroid cancer (PTC) incidence rates and the prevalence of obesity, a risk factor for PTC, have increased substantially in the United States. We estimated the proportion of PTC incidence in the United States attributable to overweight and obesity during 1995-2015.MethodsNational Institutes of Health-AARP Diet and Health Study cohort data (n = 457 331 participants, 50-71 years and cancer-free at baseline) were used to estimate multivariable-adjusted hazard ratios (HRs) for PTC across body mass index categories. Population attributable fractions (PAFs) were calculated using estimated hazard ratios and annual overweight and obesity prevalence estimates from the National Health Interview Survey. PAF estimates were combined with Surveillance, Epidemiology, and End Results-13 data to calculate annual percent changes in PTC incidence rates attributable (and unrelated) to overweight and obesity.ResultsOverweight (25.0-29.0 kg/m2) and obesity (≥30.0 kg/m2) were associated with 1.26-fold (95% confidence interval [CI] = 1.05- to 1.52-fold) and 1.30-fold (95% CI = 1.05- to 1.62-fold) increased risks of PTC, respectively, and nearly threefold (HR = 2.93, 95% CI = 1.25 to 6.87) and greater than fivefold (HR = 5.42, 95% CI = 2.24 to 13.1) increased risks of large (>4 cm) PTCs compared with normal weight (18.5-24.9 kg/m2). During 1995-2015, PAF estimates for overweight and obesity increased from 11.4% to 16.2% for all PTCs and from 51.4% to 63.2% for large PTCs. Overweight or obesity accounted for 13.6% and 57.8% of the annual percent changes in total (5.9%/y) and large (4.5%/y) PTC incidence rates, respectively, during 1995-2015.ConclusionsOverweight and obesity may have contributed importantly to the rapid rise in PTC incidence during 1995-2015. By 2015, we estimate that one of every six PTCs diagnosed among adults 60 years or older, including nearly two-thirds of large PTCs, were attributable to overweight and obesity.

BackgroundSquamous cell carcinoma of the anus (SCCA) incidence is rising in the United States. Study of incidence trends by stage at diagnosis, age-specific and birth cohort patterns, and trends in mortality could provide evidence for a true increase and etiological clues for the increase in incidence.MethodsUsing the US Cancer Statistics dataset, we examined trends in SCCA incidence (2001-2015) and mortality (2001-2016) rates. Join-point regression was used to compute annual and average annual percentage change (AAPC). Incidence patterns by 5-year age group and birth cohort were evaluated using incidence rate ratios (IRRs) and age-period-cohort modeling.ResultsSCCA incidence increased 2.7% per year (95% confidence interval [CI] = 2.1% to 3.3%), with pronounced increases in age groups 50 years and older. Distant-stage SCCA incidence tripled (AAPC = 8.6%, 95% CI = 5.4% to 12.0%, among men and AAPC = 7.5%, 95% CI = 4.8% to 10.2%, among women) and regional-stage SCCA incidence nearly doubled (AAPC = 4.7% for men and women) in both sexes; the AAPC for localized stage was 1.3% (95% CI = 0.6% to 2.0%) in men and 2.3% (95% CI = 1.8% to 2.8%) in women. Compared with adults born circa 1946, recently born black men (born circa 1986) had a nearly fivefold higher risk (IRR = 4.7, 95% CI = 2.1 to 10.2) of SCCA, and the risk doubled among white men (IRR = 2.0, 95% CI = 1.7 to 2.2) and white women (IRR = 2.1, 95% CI = 1.9 to 2.3) born after circa 1960. Anal cancer mortality rates increased 3.1% per year (95% CI = 2.6% to 3.5%) with statistically significant increases in age groups 50 years and older. SCCA incidence-based mortality increased 1.9% annually (95% CI = 0.5% to 3.4%), with a notable (4.9%, 95% CI = 2.4% to 7.3%, per year) rise in adults ages 60-69 years.ConclusionThe increase in SCCA incidence, particularly advanced-stage disease, and a similar increase in mortality suggest a true increase in the occurrence of SCCA. Future research and improved prevention are urgently needed to mitigate the increasing disease burden.

The rose-ringed parakeet has been introduced to >40 countries, gaining its status as the most widely introduced parrot in the world. Although regarded as a strikingly beautiful bird by many people, this species is a severe agricultural pest that establishes and experiences a lag time prior to exponential population growth. In addition to agricultural damage, these birds cause noise and fecal pollution, aggregate in large night roosts near human structures, may be involved in disease transfer, and, in some cases, they may help spread invasive plants. In the U.S., rose-ringed parakeets have been reported in several southern states, but established populations are in Hawaii, Florida, and California. Escapees from the pet trade probably account for most introductions, and parakeets have been reported occurring in California as early as 1956. The estimated population in Bakersfield was 3,000 birds in 2012, and additional smaller populations have been reported in San Diego, Anaheim, Santa Cruz, Malibu, and Pasadena. Much of California, excluding expansive natural areas unoccupied by humans, is potentially at risk of rose-ringed parakeet colonization, and this species represents a conceivably important threat to California agriculture. Rose-ringed parakeets are known to consume and damage crops such as rice, sunflower, safflower, rapeseed, and citrus in native India; almonds in rural Italy; and corn and fleshy fruit (e.g., guava, mangos, lychee, papaya) in Hawaii. In 1975, the California Department of Agriculture estimated that the potential crop losses due to a well-established rose-ringed parakeet population could reach US$735,000 annually, a value that resulted from an estimate of their damaging 0.1% of crops grown in the area. Rose-ringed parakeets are a serious agricultural pest in several areas outside of California, and all areas where they thrive are in human-altered landscapes. An update is needed on this species’ distribution, population changes, and impacts to agriculture within California. Furthermore, we recommend establishing an annual monitoring plan of the established California populations, as well as efforts to prevent their spread and reduce their threat to California agriculture.

Invasive rats are among the most damaging animals to native species on many island ecosystems including those in Hawaii. On Oahu Island, U.S. Army Garrison Natural Resources Program currently manages invasive rat populations to protect natural resources by using grids of A24 automated traps, and previously snap-trap grids and rodenticide bait stations. Despite these control efforts generally suppressing rats, some lands with natural resources that are at risk to rat predation are not easily accessible for implementing these traditional rat control methods. In a 430-ha mesic forest on Oahu where ungulates are excluded and site access is limited due to military training and presence of live ordnance, we tested the efficacy of aerial application of anticoagulant rodenticide bait pellets (Diphacinone-50 Conservation), applied in two applications at a rate of 12.82 kg/ha per application. We measured the effectiveness of the rodenticide bait application by deploying tracking tunnels (inked and baited cards to identify rat presence) before, during, and after applications within treated and nearby untreated areas. Due to restricted access, we failed to estimate nest success of an endangered bird; yet previous research showed rat control increases this bird’s population. We also measured diphacinone residues in stream water at the treatment site to determine this method’s risk level to the aquatic ecosystem. The aerial application resulted in immediate and sustained reduction in the rat population, as evidenced by rat activity decreasing from ~44% to 3.8% during the first three months after bait application and maintained

Since 1995, the Army’s Natural Resources Program on O‘ahu has been controlling rodents in O‘ahu’s forests to protect native plants, invertebrates, and birds. Bait longevity and attractiveness are keys to successful rodent trapping. Success is impeded when slugs interfere with bait intended for rodents. Slugs can consume all or a portion of the bait, make it less attractive to rodents via their slime, and large slugs can trigger the traps. The goal of this study was to determine whether food grade citric acid (up to 5% concentration) added to common rodent bait (i.e., commercial peanut butter and Goodnature lure) would repel slugs. We conducted several trials including where captive slugs were offered both a test (0.5-5% citric acid added) and control bait. We found slugs significantly preferred the control bait (i.e., bait without any citric acid) in the two-choice feeding experiment when the bait was Goodnature rat + mouse lure. Goodnature rat + mouse lure is the standard bait used in A24 self-resetting rat traps. The addition of citric acid may improve the longevity and attractiveness of bait to rodents in slug-inhabited environments, thereby having the potential to aid in rodent control programs.

The introduction of rodents to islands poses a threat to native fauna, which often have no adaptation to defend their offspring or themselves from predation. To combat predation of nests and brooding females, the Kauai Forest Bird Recovery Project (KFBRP) has deployed 425 Goodnature A24 self-resetting rat traps at two field sites where high densities of native forest birds remain. One site is fenced to exclude invasive ungulates. KFBRP conducts routine trap checks every four months to assess bait and trap function and count carcasses. Typically, we find 0-3 rat or mouse carcasses at a trap, but in November 2018, we found a dead bird under a trap at the fenced site. We assume that traps kill more animals than indicated by carcass counts, because 75% of traps have counters that record when traps fire, and counter tallies exceed carcass counts. Thus, we hypothesize that some carcasses are scavenged or decompose between trap checks, and as a result we are a) underestimating target mortality with carcass counts and b) failing to detect non-target mortality. To test our hypotheses, we placed 30 non-native bird carcasses on transects in the fenced trapping grid in early December 2018. Carcasses were surveyed every at 10, 20, 45, 90, and 130 days after deployed. At the end of survey period, 19 (63%) carcasses could be easily detected, suggesting that we are detecting most carcasses after four months unless they are scavenged. Furthermore, our findings suggest that we would detect non-target mortality if it was prevalent.

Beginning in 2009, the Army’s Natural Resource Program on O’ahu implemented the first of three ecosystem-scale rat trapping grids of traditional snap traps in the Waianae Mountains using the model outlined in The New Zealand Department of Conservation’s current best practices for kill-trapping rats. Traps were generally checked every two weeks, but bait often remained palatable for just a few nights due to slug interference. Because of the amount of labor required for single set traps, trials with Goodnature A24 self-resetting traps were conducted from 2014-2016. Early findings showed that traps were malfunctioning at a rate of ~25% and there were major deficiencies with the bait and bait-delivery system. In 2016 the bait system was improved when Goodnature developed the automatic lure pump that continually releases fresh bait for ~4-6 months. Other improvements were also made to the A24 trap to decrease the malfunction rate. In 2017, we replaced more than 1,300 snap traps at all ecosystem-scale grids with 1,000 A24s. Tracking tunnels were used as an independent monitoring system to determine rat control effectiveness. At all sites, rat activity measured in the tracking tunnels has been low (less than 15%) for over 18 months. In this paper we discuss the results of the transition from single- to multi-set rat traps, highlights some successes and obstacles, and describes grid spacing and applicability to other sites.

Background: Cancer survivors show low physical activity participation rates in the United States. However, there are limited national-level data on disparities in the prevalence of meeting physical activity guidelines among women with and without breast cancer. We aimed to evaluate national-level trends in meeting physical activity guidelines across demographic and socioeconomic characteristics of breast cancer survivors and women without cancer. Methods: Data for women =35 years of age with and without breast cancer were obtained from the 2004 to 2018 National Health Interview Survey. We used National Health Interview Survey sample weights to generate national-level prevalence estimates and calculate absolute and relative indices of disparity for breast cancer survivors and women without cancer meeting aerobic (150 minutes/week) and muscle-strengthening guidelines (2 sessions/week) stratified by demographic (e.g., race/ethnicity) and socioeconomic (e.g., homeownership) characteristics. Results: We included 5,845 breast cancer survivors and 160,162 women without cancer. The weighted percentage of breast cancer survivors meeting aerobic guidelines was 37.7% compared with 40.9% of women without cancer. Fewer women met muscle-strengthening guidelines. There were lower proportions of women who were younger (<50-years), were non-Hispanic Black, were Hispanic, worked 35+ hours/week, or rented their home among breast cancer survivors meeting aerobic guidelines compared with women without cancer meeting aerobic guidelines. Conclusions: Breast cancer survivors were less likely to meet physical activity guidelines compared with women without cancer. Demographic and socioeconomic disparities may exist among breast cancer survivors and women without cancer meeting physical activity guidelines. [ABSTRACT FROM AUTHOR]