Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Evaluation of Socioeconomic and Racial/Ethnic Disparities in All-Cause Mortality in Adolescents and Young Adults With Cancer.

BACKGROUND: Adolescent and young adult (AYA) patients with cancer have historically been understudied. Few studies have examined survival disparities associated with racial/ethnic and socioeconomic status (SES) and do not account for the influence of insurance status and access to care. We evaluated the association of SES and race/ethnicity with overall mortality for AYA patients who were members of an integrated health system with relatively equal access to care. METHODS: AYA patients diagnosed with the 15 most common cancer types during 2010 through 2018 at Kaiser Permanente Southern California were included. Neighborhood Deprivation Index (NDI) quartile (Q1: least deprived; Q4: most deprived) was used as a measure of SES. Mortality rate per 1,000 person-years was calculated for each racial/ethnic and NDI subgroup. Multivariable Cox model was used to estimate hazard ratios (HRs) for all-cause mortality adjusting for sex, age and stage at diagnosis, cancer type, race/ethnicity, and NDI. RESULTS: Data for 6,379 patients were tracked for a maximum of 10 years. Crude mortality rates were higher among non-White racial/ethnic patients compared with non-Hispanic (NH)-White patients. In the Cox model, Hispanic (HR, 1.31; P=.004) and NH-Black (HR, 1.34; P=.05) patients experienced significantly higher all-cause mortality risk compared with NH-White patients. Patients from more deprived neighborhoods had higher mortality risk. In the Cox model, there was no significant difference in all-cause mortality between Q1 and Q2 through Q4 (Q2: HR, 0.88; P=.26, Q3: HR, 0.94; P=.56, and Q4: HR, 0.95; P=.70). CONCLUSIONS: For AYAs with cancer with similar access to care, Hispanic and NH-Black patients have higher risk of all-cause mortality than NH-White patients, whereas no significant SES-associated survival disparities were observed. These findings warrant further investigation, awareness, and intervention to address inequities in cancer care among vulnerable populations.

Managing invasive hybrids with pond hydroperiod manipulation in an endangered salamander system.

When invasive and endangered native taxa hybridize, the resulting admixture introduces novel conservation challenges. Across a large region of central California, a hybrid swarm consisting of admixed endangered California tiger salamanders (CTS) (Ambystoma californiense) and introduced barred tiger salamanders (BTS) (Ambystoma mavortium) has replaced native populations, threatening the genetic integrity of CTS and the vernal pool systems they inhabit. We employed a large-scale, genomically informed field experiment to test whether shortening breeding pond hydroperiod would favor native CTS genotypes. We constructed 14 large, seminatural ponds to evaluate the effect of hydroperiod duration on larval survival and mass at metamorphosis. We tracked changes in non-native allele frequencies with a 5237-gene exon capture array and employed a combination of custom Bayesian and generalized linear models to quantify the effect of pond duration on salamander fitness. Earlier work on this system showed hybrid superiority under many conditions and suggested that hybrids are favored in human-modified ponds with artificially long hydroperiods. Consistent with these earlier studies, we found overwhelming evidence for hybrid superiority. Very short hydroperiods substantially reduced the mass (1.1-1.5 fold) and survival probability (10-13 fold) of both native and hybrid larvae, confirming that hydroperiod likely exerts a strong selective pressure in the wild. We identified 86 genes, representing 1.8% of 4723 screened loci, that significantly responded to this hydroperiod-driven selection. In contrast to earlier work, under our more natural experimental conditions, native CTS survival and size at metamorphosis were always less than hybrids, suggesting that hydroperiod management alone will not shift selection to favor native larval genotypes. However, shortening pond hydroperiod may limit productivity of hybrid ponds, complementing other strategies to remove hybrids while maintaining vernal pool ecosystems. This study confirms and expands on previous work that highlights the importance of hydroperiod management to control invasive aquatic species.

Manejo de híbridos invasores mediante la manipulación del hidroperiodo de los estanques en el sistema de una salamandra en peligro de extinción Resumen La hibridación entre un taxón nativo en peligro y uno invasor introduce nuevos retos para la conservación. Una plaga híbrida de salamandras tigre de California (STC) (Ambystoma californiense), especie en peligro, y salamandras tigre barradas (STB) (Ambystoma mavortium) introducidas ha reemplazado a las poblaciones nativas en una región amplia del centro de California, lo que amenaza la integridad genética de las STC y el sistema de estanques vernales que habitan. Realizamos un experimento de campo a gran escala y con información genética para probar si la reducción del hidroperiodo reproductivo del estanque favorecería al genotipo de las STC nativas. Construimos 14 estanques seminaturales grandes para analizar el efecto de la duración del hidroperiodo sobre la supervivencia y masa larval durante la metamorfosis. Monitoreamos los cambios en la frecuencia de alelos no nativos con una matriz de captura de exones de 5,237 genes y utilizamos una combinación de modelos lineales generalizados y bayesianos a medida para cuantificar los efectos de la duración del estanque sobre la adaptabilidad de las salamandras. Los primeros trabajos en este sistema mostraron la superioridad híbrida bajo varias condiciones y sugirieron que los híbridos están favorecidos en los estanques con modificaciones antropogénicas e hidroperiodos de larga duración artificial. En coherencia con estos primeros resultados, encontramos evidencia abrumadora de la superioridad híbrida. Los hidroperiodos muy cortos redujeron sustancialmente la masa (1.1­1.5 más veces) y la probabilidad de supervivencia (10­13 más veces) de las larvas nativas e híbridas, lo que confirma que el hidroperiodo probablemente ejerce una fuerte presión selectiva en vida silvestre. Identificamos 86 genes, que representan el 1.8% de los 4,723 loci examinados, que respondieron significativamente a la selección basada en el hidroperiodo. Con las condiciones más naturales de nuestro experimento, y en contraste a nuestros primeros trabajos, la supervivencia y el tamaño de las STC nativas durante la metamorfosis siempre fueron menores a las de los híbridos, lo que sugiere que el manejo del hidroperiodo por sí solo no cambiará la selección a favor de los genotipos larvales nativos. Sin embargo, la reducción del hidroperiodo del estanque puede limitar la productividad de los estanques híbridos y complementar otras estrategias para extirpar a los híbridos mientras que mantiene el ecosistema del estanque vernal. Este estudio confirma y amplía los trabajos anteriores que resaltan la importancia del manejo del hidroperiodo para controlar las especies acuáticas invasoras.

Cot-side imaging of functional connectivity in the developing brain during sleep using wearable high-density diffuse optical tomography.

Studies of cortical function in newborn infants in clinical settings are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become an increasingly common clinical research tool but has significant limitations including a low spatial resolution and poor depth specificity. Moreover, the bulky optical fibres required in traditional fNIRS approaches present significant mechanical challenges, particularly for the study of vulnerable newborn infants. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first cot-side study of newborn infants using wearable HD-DOT in a clinical setting. We use this technology to study functional brain connectivity (FC) in newborn infants during sleep and assess the effect of neonatal sleep states, active sleep (AS) and quiet sleep (QS), on resting state FC. Our results demonstrate that it is now possible to obtain high-quality functional images of the neonatal brain in the clinical setting with few constraints. Our results also suggest that sleep states differentially affect FC in the neonatal brain, consistent with prior reports.

Climate-mediated population dynamics of a migratory songbird differ between the trailing edge and range core.

Understanding the demographic drivers of range contractions is important for predicting species' responses to climate change; however, few studies have examined the effects of climate change on survival and recruitment across species' ranges. We show that climate change can drive trailing edge range contractions through the effects on apparent survival, and potentially recruitment, in a migratory songbird. We assessed the demographic drivers of trailing edge range contractions using a long-term demography dataset for the black-throated blue warbler (Setophaga caerulescens) collected across elevational climate gradients at the trailing edge and core of the breeding range. We used a Bayesian hierarchical model to estimate the effect of climate change on apparent survival and recruitment and to forecast population viability at study plots through 2040. The trailing edge population at the low-elevation plot became locally extinct by 2017. The local population at the mid-elevation plot at the trailing edge gradually declined and is predicted to become extirpated by 2040. Population declines were associated with warming temperatures at the mid-elevation plot, although results were more equivocal at the low-elevation plot where we had fewer years of data. Population density was stable or increasing at the range core, although warming temperatures are predicted to cause population declines by 2040 at the low-elevation plot. This result suggests that even populations within the geographic core of the range are vulnerable to climate change. The demographic drivers of local population declines varied between study plots, but warming temperatures were frequently associated with declining rates of population growth and apparent survival. Declining apparent survival in our study system is likely to be associated with increased adult emigration away from poor-quality habitats. Our results suggest that demographic responses to warming temperatures are complex and dependent on local conditions and geographic range position, but spatial variation in population declines is consistent with the climate-mediated range shift hypothesis. Local populations of black-throated blue warblers near the warm-edge range boundary at low latitudes and low elevations are likely to be the most vulnerable to climate change, potentially leading to local extirpation and range contractions.

Influence of Comorbidity Burden, Socioeconomic Status, and Race and Ethnicity on Survival Disparities in Patients With Cancer.

PURPOSE: The purpose of this study was to assess the association of comorbidity burden with overall survival, accounting for racial/ethnic and socioeconomic differences in patients with cancer. METHODS: In this retrospective cohort study, patients newly diagnosed with cancer between 2010 and 2018 were identified from a large health plan in southern California. Cancer registry data were linked with electronic health records (EHR). Comorbidity burden was defined by the Elixhauser comorbidity index (ECI). Patients were followed through December 2019 to assess all-cause mortality. Association of comorbidity burden with all-cause mortality was evaluated using Cox proportional hazards model. Crude and adjusted hazard ratio (HR, 95%CI) were determined. RESULTS: Of 153,270 patients included in the analysis, 29% died during the ensuing 10-year follow-up. Nearly 49% were patients of color, and 32% had an ECI > 4. After adjusting for age, sex, race/ethnicity, cancer stage, smoking status, insurance payor, medical center, year of cancer diagnosis, and cancer treatments, we observed a trend demonstrating higher mortality risk by decreasing socioeconomic status (SES) (P-trend<.05). Compared to patients in the highest SES quintile, patients in the lowest, second lowest, middle, and second highest quintiles had 25%, 21%, 18%, and 11% higher risk of mortality, respectively [(HR, 95%CI): 1.25 (1.21-1.29), 1.21 (1.18-1.25), 1.18 (1.15-1.22), and 1.11 (1.07-1.14), respectively]. When we additionally adjusted for ECI, the adjusted HRs for SES were slightly attenuated; however, the trend persisted. Patients with higher comorbidity burden had higher mortality risk compared to patients with ECI score = 0 in the adjusted model [(HR, 95%CI): 1.22 (1.17-1.28), 1.48 (1.42-1.55), 1.80 (1.72-1.89), 2.24 (2.14-2.34), and 3.39 (3.25-3.53) for ECI = 1, 2, 3, 4, and >5, respectively]. CONCLUSIONS: Comorbidity burden affects overall survival in cancer patients irrespective of racial/ethnic and SES differences. Reducing comorbidity burden can reduce some, but not all, of the mortality risk associated with lower SES.

Seasonal assessment on the effects of time of night, temperature and humidity on the biting profile of Anopheles farauti in north Queensland, Australia using a population naive to malaria vector control pressures.

BACKGROUND: Anopheles farauti is one of the major vectors of malaria in the Southwest Pacific region and is responsible for past outbreaks in Australia. With an adaptable biting profile conducive to behavioural resistance to indoor residual spraying (IRS) and insecticide-treated nets (ITNs), its all-night biting behaviour can switch to biting mostly in the early evening. With limited insight into the biting profile of An. farauti populations in areas that have not encountered IRS or ITNs, the aim of this study was to develop insights on the biting behaviour of a malaria control naive population of An. farauti. METHODS: Biting profiles of An. farauti were conducted at Cowley Beach Training Area, in north Queensland, Australia. Initially, encephalitis virus surveillance (EVS) traps were used to document the 24-h biting profile of An. farauti and then human landing collections (HLC) were used to follow the 18.00-06.00 h biting profile. The human landing catches (HLC) were performed at both the end of the wet (April) and dry (October) seasons. RESULTS: Data exploration using a Random Forest Model shows that time of night is the most important variable for predicting An. farauti biting activity. Temperature was found to be the next important predictor, followed by humidity, trip, collector, and season. The significant effect of time of night and peak in time of night biting, between 19.00 and 20.00 h was also observed in a generalized linear model. The main effect of temperature was significant and non-linear and appears to have a positive effect on biting activity. The effect of humidity is also significant but its relationship with biting activity is more complex. This population's biting profile is similar to populations found in other parts of its range prior to insecticide intervention. A tight timing for the onset of biting was identified with more variation with the end of biting, which is likely underpinned by an endogenous circadian clock rather than any light intensity. CONCLUSION: This study sees the first record of a relationship between biting activity and the decreasing temperature during the night for the malaria vector, Anopheles farauti.

Disparities in melanoma-specific mortality by race/ethnicity, socioeconomic status, and health care systems.

BACKGROUND: Despite encouraging trends in survival, sociodemographic inequalities persist among patients with melanoma. OBJECTIVE: We sought to quantify the effect of race/ethnicity, socioeconomic status, and health care systems on melanoma-specific mortality within an insured population of patients. METHODS: Using a retrospective cohort study, we identified insured adults diagnosed with Stage I to IV melanoma from January 1, 2009, to December 31, 2014, followed through 2017, from the California Cancer Registry. We compared melanoma-specific mortality between insured patients diagnosed within the largest vertically integrated health care system in California, Kaiser Permanente Southern California, and insured patients with other private insurance (OPI). RESULTS: Our cohort included 14,614 adults diagnosed with melanoma. Multivariable analyses demonstrated that race/ethnicity was not associated with survival disparities, while socioeconomic status was a strong predictor of melanoma-specific mortality, particularly for those with OPI. For example, hazard ratios demonstrate that the poorest patients with OPI have a 70% increased risk of dying from their melanoma compared to their wealthiest counterparts, while the poorest patients in Kaiser Permanente Southern California have no increased risk. LIMITATIONS: Our main limitation includes inadequate data for certain racial/ethnic groups, such as Native Americans. CONCLUSIONS: Our findings underscore the persistence of socioeconomic disparities within an insured population, specifically among those in non-integrated health care systems.

Relationships Between the Nicotine Metabolite Ratio (NMR) and Laboratory Assessments of Smoking Reinforcement and Craving Among Adults in a Smoking Cessation Trial.

INTRODUCTION: People who metabolize nicotine more quickly are generally less successful at quitting smoking. However, the mechanisms that link individual differences in the nicotine metabolite ratio (NMR), a phenotypic biomarker of the rate of nicotine clearance, to smoking outcomes are unclear. We tested the hypotheses that higher NMR is associated with greater smoking reinforcement, general craving, and cue-induced cigarette craving in a treatment-seeking sample. METHODS: Participants were 252 adults who smoke cigarettes enrolled in a randomized controlled smoking cessation trial (NCT03262662) conducted in Buffalo, New York, USA. Participants completed the Choice Behavior Under Cued Conditions (CBUCC) paradigm, a laboratory choice procedure, ~1 week before the first cessation treatment visit, at which time a saliva sample was collected for NMR assessment. On each CBUCC trial, participants reported cigarette craving during cue presentation (cigarette, water) and spent $0.01-0.25 for a chance (5%-95%) to sample the cue (1 puff, sip), providing measures of smoking reinforcement (spending for cigarettes vs. water), general cigarette craving (averaged across cigarette and water cues), and cue-specific craving (cigarette craving during cigarette vs. water cues). RESULTS: As observed in prior work, the NMR was significantly higher among white and female participants. As expected, both spending and cigarette craving were significantly greater on cigarette compared to water trials. However, contrary to our hypotheses, higher NMR was not associated with greater smoking reinforcement, general craving, or cue-specific craving. CONCLUSIONS: The present data do not support that smoking reinforcement or craving are related to nicotine metabolism among individuals seeking to quit smoking. IMPLICATIONS: Though greater smoking reinforcement, general craving, and cue-specific craving are hypothesized to be linked to faster nicotine metabolism, there was no evidence of such relationships in the present sample of adults seeking to quit smoking. Further research, including replication and consideration of alternate hypotheses, is warranted to elucidate the mechanisms by which the NMR is related to smoking cessation.

The Costs of Operating a Student-run Free Clinic.

INTRODUCTION: Free clinics provide care for those who may otherwise not have access. While this care is often free for patients, it is not free to operate such clinics. This review will provide a budget and breakdown of all expenditures at a student-run free clinic along with average costs of services provided to patients. METHODS: Accounting data was used to categorize all expenses and generate an annual budget. An inventory tracking system was developed to measure the costs of all medical supplies and services accurately, providing information on costs per clinic and costs per patient for each provided service. RESULTS: The average cost per clinic was $53.55 (per patient: $2.14) for general clinic supplies, $43.74 (per patient: $7.29) for telehealth, $278.47 (per patient: $12.66) for laboratory services, $247.25 (per patient: $10.75) for pharmacy services, and $8.30 (per patient: $1.19) for social work. These costs contributed to a relative minority (< 33%) of the total costs to run a free clinic, where the highest costs were for volunteer appreciation and administrative overhead. Twelve categories of expenditures (administrative overhead, volunteer appreciation, medical and lab supplies, conferences and special projects, advertising and marketing, telehealth, pharmacy, specialty clinics, chronic care, patient transportation, social work, and accounting services) were ranked in order of necessity, and methods for cost reduction were discussed for each category. CONCLUSIONS: Categorizing costs can show where cost savings and cost-effective additions may be implemented. This study may serve as a financial and budgeting reference for other clinics.