Estimate and needs of the transgender adult population: the SPoT study.

BACKGROUND: Despite the increasing interest in transgender health research, to date little is known about the size of the transgender and gender diverse (TGD) population. METHODS: A web-based questionnaire survey was developed, including a collection of socio-demographic characteristics and disseminated online through social media. Gender incongruence was evaluated by using a 2-item approach assessing gender recorded at birth and gender identity. The primary objective of the present population-based study was to estimate the proportion of TGD people across ages among a large sample of people who answered a web-based survey. The secondary endpoints were to identify gender-affirming needs and possible barriers to healthcare access. RESULTS: A total of 19,572 individuals participated in the survey, of whom 7.7% reported a gender identity different from the sex recorded at birth. A significantly higher proportion of TGD people was observed in the youngest group of participants compared with older ones. Among TGD people who participated in the study, 58.4% were nonbinary, and 49.1% experienced discrimination in accessing health care services. Nonbinary TGD participants reported both the need for legal name and gender change, along with hormonal and surgical interventions less frequently compared to binary persons. CONCLUSIONS: Being TGD is not a marginal condition In Italy. A large proportion of TGD persons may not need medical and surgical treatments. TGD people often experience barriers to healthcare access relating to gender identity.

General Strategy for Incorporation of Functional Group Handles into Covalent Organic Frameworks via the Ugi Reaction.

The library of imine-linked covalent organic frameworks (COFs) has grown significantly over the last two decades, featuring a variety of morphologies, pore sizes, and applications. An array of synthetic methods has been developed to expand the scope of the COF functionalities; however, most of these methods were designed to introduce functional scaffolds tailored to a specific application. Having a general approach to diversify COFs via late-stage incorporation of functional group handles would greatly facilitate the transformation of these materials into platforms for a variety of useful applications. Herein, we report a general strategy to introduce functional group handles in COFs via the Ugi multicomponent reaction. To demonstrate the versatility of this approach, we have synthesized two COFs with hexagonal and kagome morphologies. We then introduced azide, alkyne, and vinyl functional groups, which could be readily utilized for a variety of post-synthetic modifications. This facile approach enables the functionalization of any COFs containing imine linkages.

AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity.

BACKGROUND & AIMS: Pharmacological management of obesity improves outcomes and decreases the risk of obesity-related complications. This American Gastroenterological Association guideline is intended to support practitioners in decisions about pharmacological interventions for overweight and obesity. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis of the following agents: semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 oral superabsorbent hydrogel. The guideline panel used the evidence-to-decision framework to develop recommendations for the pharmacological management of obesity and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 9 recommendations. The panel strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity (body mass index ≥30 kg/m2, or ≥27 kg/m2 with weight-related complications) who have an inadequate response to lifestyle interventions. The panel suggested the use of semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER (based on moderate certainty evidence), and phentermine and diethylpropion (based on low certainty evidence), for long-term management of overweight and obesity. The guideline panel suggested against the use of orlistat. The panel identified the use of Gelesis100 oral superabsorbent hydrogel as a knowledge gap. CONCLUSIONS: In adults with overweight and obesity who have an inadequate response to lifestyle interventions alone, long-term pharmacological therapy is recommended, with multiple effective and safe treatment options.

Non-Steady-State Fickian Diffusion Models Decrease the Estimated Gel Layer Diffusion Coefficient Uncertainty for Diffusive Gradients in Thin-Films Passive Samplers.

Mass transport in diffusive gradients in thin-film passive samplers is restricted to diffusion through a gel layer of agarose or agarose cross-linked polyacrylamide (APA). The gel layer diffusion coefficient, DGel, is typically determined using a standard analysis (SA) based on Fick's first law from two-compartment diffusion cell (D-Cell) tests. The SA assumes pseudo-steady-state flux, characterized by linear sink mass accumulation-time profiles with a typical threshold R2 ≥ 0.97. In 72 D-Cell tests with nitrate, 63 met this threshold, but the SA-determined DGel ranged from 10.1 to 15.8 × 10-6 cm2·s-1 (agarose) and 9.5 to 14.7 × 10-6 cm2·s-1 (APA). A regression model developed with the SA to account for the diffusive boundary layer had 95% confidence intervals (CIs) on DGel of 13 to 18 × 10-6 cm2·s-1 (agarose) and 12 to 19 × 10-6 cm2·s-1 (APA) at 500 rpm. A finite difference model (FDM) developed based on Fick's second law with non-steady-state (N-SS) flux decreased uncertainty in DGel tenfold. The FDM-captured decreasing source compartment concentrations and N-SS flux in the D-Cell tests and, at 500 rpm, the FDM-determined DGel ± 95% CIs were 14.5 ± 0.2 × 10-6 cm2·s-1 (agarose) and 14.0 ± 0.3 × 10-6 cm2·s-1 (APA), respectively.

All-cause mortality during the influenza season 2019-2020: comparison with previous influenza seasons in the territory of the local health authority "Central Tuscany", Italy.

Introduction: Because of the 24 months latency in the release of official data on causes of death, and in consideration of the limited testing capacity during the first pandemic wave, to estimate the COVID-19-related mortality in 2020, the evaluation of all-cause mortality excess is often used instead. Our study aimed at assessing whether in Central Tuscany, Italy, an excess all-cause mortality occurred in the 2019-2020 influenza season, which partly overlapped with the months of the first pandemic wave in which the impact of COVID-19 was the highest. Materials and Methods: Age- and sex-adjusted mortality rates for 2019-2020 influenza season were compared with those of influenza seasons 2009-2010 to 2016-2017. Results: No all-cause mortality excess was observed in the 2019-2020 influenza season, which, on the contrary, was characterized by the lowest all-cause mortality rate. Conclusion: Our finding can be explained by the imposition, in early March 2020, of a national lockdown, which came into effect in an early epidemic phase in Tuscany, and thus limited the transmission of SARS-CoV-2 infection, as well as influenza, in the territory. In March and April, by causing the death of vulnerable elderly patients who had been spared by the mild seasonal flu in the prior months, COVID-19 acted with a harvesting effect.

The Wiring Logic of an Identified Serotonergic Neuron That Spans Sensory Networks.

Serotonergic neurons project widely throughout the brain to modulate diverse physiological and behavioral processes. However, a single-cell resolution understanding of the connectivity of serotonergic neurons is currently lacking. Using a whole-brain EM dataset of a female Drosophila, we comprehensively determine the wiring logic of a broadly projecting serotonergic neuron (the CSDn) that spans several olfactory regions. Within the antennal lobe, the CSDn differentially innervates each glomerulus, yet surprisingly, this variability reflects a diverse set of presynaptic partners, rather than glomerulus-specific differences in synaptic output, which is predominately to local interneurons. Moreover, the CSDn has distinct connectivity relationships with specific local interneuron subtypes, suggesting that the CSDn influences distinct aspects of local network processing. Across olfactory regions, the CSDn has different patterns of connectivity, even having different connectivity with individual projection neurons that also span these regions. Whereas the CSDn targets inhibitory local neurons in the antennal lobe, the CSDn has more distributed connectivity in the LH, preferentially synapsing with principal neuron types based on transmitter content. Last, we identify individual novel synaptic partners associated with other sensory domains that provide strong, top-down input to the CSDn. Together, our study reveals the complex connectivity of serotonergic neurons, which combine the integration of local and extrinsic synaptic input in a nuanced, region-specific manner.SIGNIFICANCE STATEMENT All sensory systems receive serotonergic modulatory input. However, a comprehensive understanding of the synaptic connectivity of individual serotonergic neurons is lacking. In this study, we use a whole-brain EM microscopy dataset to comprehensively determine the wiring logic of a broadly projecting serotonergic neuron in the olfactory system of Drosophila Collectively, our study demonstrates, at a single-cell level, the complex connectivity of serotonergic neurons within their target networks, identifies specific cell classes heavily targeted for serotonergic modulation in the olfactory system, and reveals novel extrinsic neurons that provide strong input to this serotonergic system outside of the context of olfaction. Elucidating the connectivity logic of individual modulatory neurons provides a ground plan for the seemingly heterogeneous effects of modulatory systems.

Nickel-Catalyzed Asymmetric Hydroarylation of Vinylarenes: Direct Enantioselective Synthesis of Chiral 1,1-Diarylethanes.

The enantioselective hydroarylation of vinylarenes catalyzed by a chiral, non-racemic nickel catalyst is presented as a facile method to generate chiral 1,1-diarylethanes. These reactions proceed via formation of a chiral, non-racemic nickel benzyl intermediate. Transmetalation with arylboron nucleophiles and subsequent reductive elimination enable the formation of a variety of chiral 1,1-diarylethanes. The 1,1-diarylethane products from reactions of arylboronic acids containing electron-donating substituents are formed with typically greater than 90% ee, while the 1,1-diarylethanes generated from reactions of arylboronic acids containing electron-withdrawing groups are generated with typically less than 80% ee. These results are consistent with the rate of transmetalation with an arylboron nucleophile playing a key role in the enantioselectivity of these hydroarylation reactions. This mechanistic insight has led to the development of reactions of neo-pentylglycolate esters of arylboronic acids with vinylarenes that occur with higher enantioselectivities based on increased rates of transmetalation.

Palladium-Catalyzed Intermolecular Acylative Heck Reactions with Imides as Acyl Electrophiles.

We disclose palladium-catalyzed, intermolecular, acylative Heck reactions that use imides as acyl electrophiles. The catalyst generated from [Pd(allyl)Cl]2 and DPEphos promotes the reaction between N-benzoylglutarimides and norbornene in the presence of silver phosphate. The acylative Heck reaction encompasses an array of N-benzoylglutarimide electrophiles that contain electron-donating, halogenated, and electron-withdrawing substituents to generate α,ß-unsaturated ketones in moderate to high yields (25-82%). The bicylic α,ß-unsaturated ketones are readily transformed into polycyclic architectures via thermal hetero-Diels-Alder reactions that occur by the dimerization of the α,ß-unsaturated ketones.

Ammonia Dry Deposition in an Alpine Ecosystem Traced to Agricultural Emission Hotpots.

Elevated reactive nitrogen (Nr) deposition is a concern for alpine ecosystems, and dry NH3 deposition is a key contributor. Understanding how emission hotspots impact downwind ecosystems through dry NH3 deposition provides opportunities for effective mitigation. However, direct NH3 flux measurements with sufficient temporal resolution to quantify such events are rare. Here, we measured NH3 fluxes at Rocky Mountain National Park (RMNP) during two summers and analyzed transport events from upwind agricultural and urban sources in northeastern Colorado. We deployed open-path NH3 sensors on a mobile laboratory and an eddy covariance tower to measure NH3 concentrations and fluxes. Our spatial sampling illustrated an upslope event that transported NH3 emissions from the hotspot to RMNP. Observed NH3 deposition was significantly higher when backtrajectories passed through only the agricultural region (7.9 ng m-2 s-1) versus only the urban area (1.0 ng m-2 s-1) and both urban and agricultural areas (2.7 ng m-2 s-1). Cumulative NH3 fluxes were calculated using observed, bidirectional modeled, and gap-filled fluxes. More than 40% of the total dry NH3 deposition occurred when air masses were traced back to agricultural source regions. More generally, we identified that 10 (25) more national parks in the U.S. are within 100 (200) km of an NH3 hotspot, and more observations are needed to quantify the impacts of these hotspots on dry NH3 deposition in these regions.

Systematic and standardized comparison of reported amyloid-ß receptors for sufficiency, affinity, and Alzheimer's disease relevance.

Oligomeric assemblies of amyloid-ß (Aß) peptide (Aßo) in the brains of individuals with Alzheimer's disease (AD) are toxic to neuronal synapses. More than a dozen Aß receptor candidates have been suggested to be responsible for various aspects of the molecular pathology and memory impairment in mouse models of AD. A lack of consistent experimental design among previous studies of different receptor candidates limits evaluation of the relative roles of these candidates, producing some controversy within the field. Here, using cell-based assays with several Aß species, including Aßo from AD brains obtained by autopsy, we directly compared the Aß-binding capacity of multiple receptor candidates while accounting for variation in expression and confirming cell surface expression. In a survey of 15 reported Aß receptors, only cellular prion protein (PrPC), Nogo receptor 1 (NgR1), and leukocyte immunoglobulin-like receptor subfamily B member 2 (LilrB2) exhibited direct binding to synaptotoxic assemblies of synthetic Aß. Both PrPC and NgR1 preferentially bound synaptotoxic oligomers rather than nontoxic monomers, and the method of oligomer preparation did not significantly alter our binding results. Hippocampal neurons lacking both NgR1 and LilrB2 exhibited a partial reduction of Aßo binding, but this reduction was lower than in neurons lacking PrPC under the same conditions. Finally, binding studies with soluble Aßo from human AD brains revealed a strong affinity for PrPC, weak affinity for NgR1, and no detectable affinity for LilrB2. These findings clarify the relative contributions of previously reported Aß receptors under controlled conditions and highlight the prominence of PrPC as an Aß-binding site.

Variability of Ammonia and Methane Emissions from Animal Feeding Operations in Northeastern Colorado.

Concentrated animal feeding operations (CAFOs) are major emitters of both ammonia (NH3) and methane (CH4). However, current emission inventories have limited temporal resolution and use data derived from a small subset of farms. To this end, we deployed three mobile laboratories during the DISCOVER-AQ campaign in summer 2014 with a focus on northeastern Colorado. Observations of NH3 and CH4 plumes downwind of 43 CAFOs were used to investigate the diurnal and site-to-site variability of emissions with an inverse area source plume modeling approach. Ammonia emissions scaled to all permitted animals in Weld, Morgan, and Larimer counties were estimated at 1.9 Gg month-1, 50% greater than the U.S. NEI 2014 and 360% greater than EDGAR for the month of August. Methane emissions were likewise estimated at 10.6 Gg month-1, consistent with the U.S. GHGI but 99% greater than EDGAR. Significant differences between individual CAFOs with repeat observations were also observed for both CH4 and NH3 emissions. The large subfarm, site-to-site, and diurnal variabilities observed show the importance of measurements taken across these scales in order to derive representative emission factors.

Importance of Superemitter Natural Gas Well Pads in the Marcellus Shale.

A large-scale study of methane emissions from well pads was conducted in the Marcellus shale (Pennsylvania), the largest producing natural gas shale play in the United States, to better identify the prevalence and characteristics of superemitters. Roughly 2100 measurements were taken from 673 unique unconventional well pads corresponding to ∼18% of the total population of active sites and ∼32% of the total statewide unconventional natural gas production. A log-normal distribution with a geometric mean of 2.0 kg h-1 and arithmetic mean of 5.5 kg h-1 was observed, which agrees with other independent observations in this region. The geometric standard deviation (4.4 kg h-1) compared well to other studies in the region, but the top 10% of emitters observed in this study contributed 77% of the total emissions, indicating an extremely skewed distribution. The integrated proportional loss of this representative sample was equal to 0.53% with a 95% confidence interval of 0.45-0.64% of the total production of the sites, which is greater than the U.S. Environmental Protection Agency inventory estimate (0.29%), but in the lower range of other mobile observations (0.09-3.3%). These results emphasize the need for a sufficiently large sample size when characterizing emissions distributions that contain superemitters.

Numerical Model for Decontamination of Organic Contaminants in Polyethylene Drinking Water Pipes in Premise Plumbing by Flushing.

Polymeric materials such as polyethylene are used extensively for indoor drinking water applications. These materials are subject to permeation by organic compounds such as those found in petroleum products and industrial chemicals, which can result in water quality issues with potential health effects. Although flushing is a common decontamination technique, disagreements and knowledge gaps in the scientific literature complicate prediction of how much flushing may be required to address organic contamination incidents. This paper utilizes a numerical solution to the diffusion equation to predict flushing decontamination times for toluene in cross-linked polyethylene tubing. Results suggest that for premise plumbing materials typically used for indoor drinking water applications, contaminated polyethylene tubing can be resistant to decontamination by flushing, possibly requiring days of continuous flushing to achieve contaminant removal to below regulatory levels.

An Acid-Catalyzed Addition and Dehydration Sequence for the Synthesis of Heteroarylated Steroidal Dienes.

Additions of heteroarenes to hormone steroids containing an α,ß-unsaturated ketone are reported. Additions of a range of electron-rich heteroarene nucleophiles, including indoles, a pyrrole, and a thiophene, to a variety of commercially available steroids and subsequent dehydration formed 3-heteroarylated steroidal dienes in up to 93% yield. This atom-economical reaction sequence occurs under mild reaction conditions in the presence of catalytic bismuth triflate.

Ni-Catalyzed Alkene Carboacylation via Amide C-N Bond Activation.

We report Ni-catalyzed formal carboacylation of o-allylbenzamides with arylboronic acid pinacol esters. The reaction is triggered by oxidative addition of an activated amide C-N bond to a Ni(0) catalyst and proceeds via alkene insertion into a Ni(II)-acyl bond. The exo-selective carboacylation reaction generates 2-benzyl-2,3-dihydro-1H-inden-1-ones in moderate to high yields (46-99%) from a variety of arylboronic acid pinacol esters and substituted o-allylbenzamides. These results show that amides are practical substrates for alkene carboacylation via amide C-N bond activation, and this approach bypasses challenges associated with alkene carboacylation triggered by C-C bond activation.

Vehicle Emissions as an Important Urban Ammonia Source in the United States and China.

Ammoniated aerosols are important for urban air quality, but emissions of the key precursor NH3 are not well quantified. Mobile laboratory observations are used to characterize fleet-integrated NH3 emissions in six cities in the U.S. and China. Vehicle NH3:CO2 emission ratios in the U.S. are similar between cities (0.33-0.40 ppbv/ppmv, 15% uncertainty) despite differences in fleet composition, climate, and fuel composition. While Beijing, China has a comparable emission ratio (0.36 ppbv/ppmv) to the U.S. cities, less developed Chinese cities show higher emission ratios (0.44 and 0.55 ppbv/ppmv). If the vehicle CO2 inventories are accurate, NH3 emissions from U.S. vehicles (0.26 ± 0.07 Tg/yr) are more than twice those of the National Emission Inventory (0.12 Tg/yr), while Chinese NH3 vehicle emissions (0.09 ± 0.02 Tg/yr) are similar to a bottom-up inventory. Vehicle NH3 emissions are greater than agricultural emissions in counties containing near half of the U.S. population and require reconsideration in urban air quality models due to their colocation with other aerosol precursors and the uncertainties regarding NH3 losses from upwind agricultural sources. Ammonia emissions in developing cities are especially important because of their high emission ratios and rapid motorizations.

Technique developments and performance analysis of chirped-probe-pulse femtosecond coherent anti-Stokes Raman scattering combustion thermometry.

This work characterizes the state of the art in the analysis of high-repetition-rate, ultrafast combustion thermometry using chirped-probe-pulse femtosecond coherent anti-Stokes Raman scattering (CPP fs-CARS). Several key aspects of the CARS spectroscopy system are described, including: (1) the ultrafast laser source, (2) use of the frequency-doubled idler versus signal from the optical parametric amplifier, (3) the geometry constraints for phase matching, and (4) spectral fitting for single-shot temperature measurements. A frequency-dependent instrument response function (IRF) for the detection system was modeled as a variable-width Gaussian and implemented through a frequency convolution of synthetic spectra. Proper accounting of the IRF increased spectral fitting performance in the high-frequency region where signal oscillations are weaker and narrower. Aggregated data from 25 system performance assessments taken over four months yielded accuracy and precision of 2.7% and ±3.5% for flame temperatures, and 9.9% and ±6.1% at room temperature, using the commonly reported method. A new processing technique, based on the statistical method of maximum likelihood, was implemented for turbulent flames where strong fluctuations in expected temperatures necessitate use of multiple temperature calibrations. Results from multiple sets of laser parameters are combined to generate an error-weighted temperature from the top-performing calibrations. A testing procedure was designed to characterize system performance when the range of expected temperatures is unknown, simulating the random temperature field of a highly turbulent flame. Accuracy error of the CPP fs-CARS system increased in this more-stressing test at all temperatures, but precision was significantly affected only at room temperature. System stability is characterized, and the contribution from shot-to-shot laser fluctuations on measurement precision is quantified. Finally, the near-adiabatic and steady assumptions for the Hencken burner calibration flame are examined in an axial scan; significant deviations from ideal behavior were observed only at heights of more than four diameters above the burner surface.

Growth Plate Lesions of Fattening Bulls.

Lameness related to growth plate lesions is an important problem in the beef industry. This article describes the macroscopic and microscopic lesions in the distal metatarsal physis of bulls from an association of farmers in northeastern Italy. The metatarsal bones of 62 bulls (12 with severe lameness and 50 without lameness), average age 16.44 ± 1.72 months, were examined at the abattoir. The animals came from the same geographic area and shared intensive husbandry practices and a diet based on maize starch. A total of 124 metatarsal bones were sectioned, and the distal metaphyseal growth plate was grossly examined. Twenty-three cases, including 12 lame and 9 nonlame animals with visible lesions on macroscopic examination, and 2 controls (a total of 46 physes) were examined microscopically. Eight of 12 bulls with severe lameness had a chronic purulent physitis in at least 1 limb. Segmental thickening of the hypertrophic zone, consistent with osteochondrosis (OC), was present contralaterally ( n = 3 cases) and bilaterally ( n = 3 cases) in 6 of these animals. In the group of nonlame bulls, 19 of 50 (38%) had similar segmental thickening of the physis consistent with OC. In the remaining bulls, minor findings included partial closure of the physis and a variable degree of metaphyseal hyperemia. A high incidence of OC was found in both lame and nonlame fattening bulls. It is likely that lame animals were clinically more severe due to secondary hematogenous implantation of bacteria, resulting in a purulent physitis and severe lameness that required emergency slaughter in some cases.

Reassessment of the succession of lactic acid bacteria in commercial cucumber fermentations and physiological and genomic features associated with their dominance.

A compositional re-assessment of the microbiota present in commercial cucumber fermentation using culture independent and dependent methods was conducted, with emphasis on lactic acid bacteria (LAB). Two commercial cucumber fermentation tanks were monitored by measuring pH, dissolved oxygen and temperature, and used as sources of samples for microbial plating, genomic DNA extraction and measurement of organic acids and carbohydrates by HPLC. Six additional commercial tanks were included to identify the dominant microorganisms using molecular methods. A comparative analysis of the publically available genome sequences corresponding to the LAB found in cucumber fermentations was completed to gain an understanding of genomic features possibly enabling dominance. Analyses of the microbiota suggest Lactobacillales prevail in cucumber fermentations, including in order of prevalence Lactobacillus pentosus, Lb. plantarum, Lb. brevis, Weissella spp., Pediococcus ethanolidurans, Leuconostoc spp. and Lactococcus spp. It was observed that Lb. pentosus and Lb. plantarum have comparatively larger genomes, higher gene counts, uniquely distribute the ribosomal clusters across the genome as opposed to close to the origin of replication, and possess more predicted amino acids prototrophies and selected biosynthesis related genes. It is theorized that Lb. pentosus and Lb. plantarum dominance in cucumber fermentations is the result of their genetic make-up.