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Oropharyngeal cancer is increasingly caused by human papillomavirus (HPV), and this increase is believed to be caused by changing sexual behaviour. It has been hypothesised that an immune response to HPV through sexual intercourse is much stronger than an immune response elicited from oral sex. Therefore, people who have their debut of oral sex before or at the same time as sexual intercourse would have a weaker immune response to HPV and hence be more likely to develop a persistent oral HPV infection and oropharyngeal cancer. Drake et al (Cancer. 2021;127[7]:1029-1038) found some evidence that supported this hypothesis. We have reanalysed two of our Australian cohorts with similar data in order to provide a perspective of Drake and colleagues' publication, as sexual behaviour varies depending on culture and geographical location. We found that engaging in oral sex (OR 4.46, 95% CI [1.88-10.62]) and being younger than 20 years at oral sex debut (OR 9.46, 95% CI [3.53-25.31]) were both very strong risk factors for oropharyngeal cancer. Participants in the general population cohort who had their sexual intercourse debut before the age of 18 were more likely to be oral HPV positive (OR 2.69, 95% CI [1.50-4.83]). Oral sex debut before sexual intercourse debut was quite uncommon in our two Australian cohorts. However, timing of or sexual debuts may further add to risks of oropharyngeal cancer, and future studies should be designed to investigate timing and order of sexual debuts to help clarify the roles of these potential causal factors.

The World Meteorological Organization Aircraft Meteorological Data Relay (AMDAR) programme refers to meteorological data gathered by commercial aircraft and made available to weather services. It has become a major source of upper-air observations whose assimilation into global models has greatly improved their performance. Near busy airports, AMDAR data generate semi-continuous vertical profiles of temperature and winds, which have been utilized to produce climatologies of atmospheric-boundary-layer (ABL) heights and general characterizations of specific cases. We analyze 2017–2019 AMDAR data for Santiago airport, located in the centre of a $$40\times 100$$ 40 × 100 km$$^2$$ 2 subtropical semi-arid valley in central Chile, at the foothills of the Andes. Profiles derived from AMDAR data are characterized and validated against occasional radiosondes launched in the valley and compared with routine operational radiosondes and with reanalysis data. The cold-season climatology of AMDAR temperatures reveals a deep nocturnal inversion reaching up to 700 m above ground level (a.g.l.) and daytime warming extending up to 1000 m a.g.l. Convective-boundary-layer (CBL) heights are estimated based on AMDAR profiles and the daytime heat budget of the CBL is assessed. The CBL warming variability is well explained by the surface sensible heat flux estimated with sonic anemometer measurements at one site, provided advection of the cool coastal ABL existing to the west is included. However, the CBL warming accounts for just half of the mean daytime warming of the lower troposphere, suggesting that rather intense climatological diurnal subsidence affects the dynamics of the daytime valley ABL. Possible sources of this subsidence are discussed.

IntroductionSolid organ transplant recipients (SOTRs) are at much higher risk of developing squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), compared to the general population. Previous studies have derived genetics-based predictors (polygenic risk scores, PRS) of SCC and BCC risk in SOTRs by assuming that genetic risk variants act in the same way in the general population as in SOTRs, but this assumption has not been fully tested.ObjectiveTo investigate whether known genetic risk variants for SCC and BCC have different effect sizes in SOTRs versus in non-transplantees, and if a re-weighted PRS would improve risk prediction.MethodsWe conducted genome-wide association studies for SCC and BCC separately in the non-transplant general population and in SOTRs, and compared the risks associated with selected common genetic variants for KC risk in SOTR vs non-transplant individuals from the UK Biobank. For regions with an increased log odds ratio in SOTRs, PRSs including these weights were validated in the QSkin study, and applied to the Australian STAR SOTR cohort.ResultsEffect sizes for functional variants in MC1R (rs1805007),ASIP(rs6059655), andIRF4(rs12203592) were much more strongly associated with the risk of KC in SOTRs than in non-transplantees. The proportional increase in the effect sizes ranged from 1.9-fold for rs6059655 and BCC risk (SOTRs log (OR)=0.49, 95%CI=0.00-0.98 vs log (OR)=0.26, 95%CI=0.24-0.30 in non-transplantees) to as high as 4.8-fold for rs1805007 and SCC risk (SOTR log (OR)=0.88, 95% CI=0.41-1.35 vs log (OR)=0.18, 95% CI=0.12-0.24 in non-transplantees). PRS with SOTR derived weights for these SNPs showed improved SCC/BCC risk stratification in the STAR Cohort, with the optimised PRS reclassifying 19% of SCC cases vs 8% using the standard PRS, and 18% of BCC cases vs 12% using the standard PRS.ConclusionEffect sizes for SCC and BCC risk for genetic variants in theMC1R, ASIP and IRF4genes are elevated in SOTRs, and correctly weighting these variants improves risk stratification based on polygenic risk.

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.

Background Melanoma incidence has been rising in populations with predominantly European ancestry (White), speculated to be partly driven by heightened detection of indolent tumors. If in situ melanomas are destined to evolve to invasive cancers, detecting and removing them should deplete the pool of invasive lesions, and people with in situ melanoma should, on average, be younger than those with invasive melanoma. Methods We analyzed long-term incidence trends (1982-2018) for in situ and invasive melanomas in 3 predominantly White populations with high, medium, and low melanoma rates: Queensland (Australia), United States White, and Scotland. We calculated the incidence rate ratio (IRR) of in situ to invasive melanomas and estimated the contributions of age, period, and cohort effects. We compared age at diagnosis of in situ vs invasive melanomas overall and stratified by sex and anatomic site. Results In all 3 populations, the in situ to invasive incidence rate ratio increased statistically significantly from less than 0.3 in 1982 to 1.95 (95% confidence interval [CI] = 1.88 to 2.02) in Queensland, 0.93 (95% CI = 0.90 to 0.96) in the US White population, and 0.58 (95% CI = 0.54 to 0.63) in Scotland in 2018. The mean age at diagnosis of in situ melanomas was the same or higher than invasive melanomas for almost all time periods among men and women and on all body sites except the lower limbs. Conclusions The increasing ratio of in situ to invasive melanoma incidence over time, together with the high (and increasing) mean age at diagnosis of in situ melanomas, is consistent with more indolent lesions coming to clinical attention than in previous eras.

Ten years of almost continuous observations at the highest Global Atmosphere Watch Regional station in the world are presented here. The Chacaltaya observatory (5240 m asl, 16.3ºS, 68.1ºW) was set up in December 2011. It is currently the only operational station characterizing optical and chemical properties of climate-relevant aerosol and gases in Bolivia and in a radius of about 1500 kilometers from the station. The observations show a clear influence of the well-marked dry and wet meteorological seasons. In addition, the impact on the Andean mountains of long and mid-range transport of biomass burning products from the lowlands is clearly recorded in different parameters measured at the station. Furthermore, the nearby presence of the largest metropolitan area in the region (~1.8 million inhabitants) is observed almost on a daily basis, and therefore different campaigns were carried out to characterize the area and its influence on our measurements. Specific results from these campaigns are discussed elsewhere. Finally, the topographic complexity represents an important challenge for modeling efforts in order to understand sources and sinks (and associated processes) of the observed parameters, requiring not only high spatial resolution and the correct choice of model options, but a novel way of interpreting these results. The decade of collaboration of an international consortium made it possible to keep the station running successfully. The challenge is now to preserve its functioning for the coming decades in a region with historically few high-quality observations while disrupting environmental and socio-economic changes take place.

Meta-analysis is pervasively used to combine multiple genome-wide association studies (GWAS) into a more powerful whole. To resolve causal variants, meta-analysis studies typically apply summary statistics-based fine-mapping methods as they are applied to single-cohort studies. However, it is unclear whether heterogeneous characteristics of each cohort (e.g., ancestry, sample size, phenotyping, genotyping, or imputation) affect fine-mapping calibration and recall. Here, we first demonstrate that meta-analysis fine-mapping is substantially miscalibrated in simulations when different genotyping arrays or imputation panels are included. To mitigate these issues, we propose a summary statistics-based QC method, SLALOM, that identifies suspicious loci for meta-analysis fine-mapping by detecting outliers in association statistics based on ancestry-matched local LD structure. Having validated SLALOM performance in simulations and the GWAS Catalog, we applied it to 14 disease endpoints from the Global Biobank Meta-analysis Initiative and found that 67% of loci showed suspicious patterns that call into question fine-mapping accuracy. These predicted suspicious loci were significantly depleted for having likely causal variants, such as nonsynonymous variants, as a lead variant (2.7x; Fisher’s exact P = 7.3 × 10−4). Compared to fine-mapping results in individual biobanks, we found limited evidence of fine-mapping improvement in the GBMI meta-analyses. Although a full solution requires complete synchronization across cohorts, our approach identifies likely spurious results in meta-analysis fine-mapping. We urge extreme caution when interpreting fine-mapping results from meta-analysis.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common forms of skin cancer. There is genetic overlap between skin cancers, pigmentation traits, and autoimmune diseases. We use linkage disequilibrium score regression to identify 20 traits (melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers) with a high genetic correlation (rg > 10%, P < 0.05) with BCC (20,791 cases and 286,893 controls in the UK Biobank) and SCC (7,402 cases and 286,892 controls in the UK Biobank), and use a multi-trait genetic analysis to identify 78 and 69 independent genome-wide significant (P < 5 × 10-8) susceptibility loci for BCC and SCC respectively; 19 BCC and 15 SCC loci are both novel and replicated (P < 0.05) in a large independent cohort; 23andMe, Inc (BCC: 251,963 cases and 2,271,667 controls, and SCC: 134,700 cases and 2,394,699 controls. Novel loci are implicated in BCC/SCC development and progression (e.g. CDKL1), pigmentation (e.g. DSTYK), cardiometabolic pathways (e.g. FADS2), and immune-regulatory pathways including; innate immunity against coronaviruses (e.g. IFIH1), and HIV-1 viral load modulation and disease progression (e.g. CCR5). We also report a powerful and optimised BCC polygenic risk score that enables effective risk stratification for keratinocyte cancer in a large prospective Canadian Longitudinal Study of Aging (794 cases and 18139 controls); e.g. percentage of participants reclassified; MTAGPRS = 36.57%, 95% CI = 35.89-37.26% versus UKBPRS= 33.23%, 95% CI=32.56-33.91%).

Raco is the local name given to a strong (gusts up to 17 m s−1), warm, and dry down-valley wind observed at the exit of the Maipo River Canyon in central Chile. Its climatology is documented based on eight years of surface measurements near the canyon exit together with a more complete characterization of its structure during an intensive observational period (IOP) carried out in July 2018. Raco winds occur in the cold season under well-defined synoptic conditions, beginning abruptly at any time during the night, reaching maximum hourly averages around 10 m s−1, and terminating around noon with the onset of afternoon westerly up-valley winds. About 25% of the days in May–August have more than six raco hours between 0100 and 1200 LT, and raco episodes last typically 1–2 days. The sudden appearance of raco winds at the surface can be accompanied by conspicuous warming (up to 10°C) and drying (up to 3 g kg−1). Raco winds are associated with a strong along-canyon pressure gradient, a regional pressure fall, and clear skies. During the IOP, radiosondes launched from both extremes of the canyon exit corridor showed a nocturnal easterly jet at 700 m AGL that occasionally descended rapidly to the surface, producing the raco. Transects along the canyon performed with a mobile ceilometer revealed a sharp frontlike feature between the cold pool over the Santiago Valley and the raco-affected conditions in the Maipo Canyon. Possible factors producing the easterly jet aloft and its occasional descent toward the surface are discussed, and a gap-wind mechanism is postulated to be at work.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced individuals (6,538 ALS patients, 2,415 controls) and the largest cortex-derived eQTL dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, repeat expansions or regulatory effects. ALS associated risk loci were shared with multiple traits within the neurodegenerative spectrum, but with distinct enrichment patterns across brain regions and cell-types. Across environmental and life-style risk factors obtained from literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. All ALS associated signals combined reveal a role for perturbations in vesicle mediated transport and autophagy, and provide evidence for cell-autonomous disease initiation in glutamatergic neurons.

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible., Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

Height of the stable boundary layer (SBL) presents an important diagnostic used to describe the relevant processes governing the evolution and characteristics of SBL, and the extent to which the surface is communicating with the free atmosphere. Here we investigate the SBL height over a gentle (1°) mesoscale slope on which relatively deep mid-latitude katabatic flows (with jet maxima between 20 and 50 m) develop during clear nights. We show that detecting the SBL top depends on the method used (Richardson number, flux- and anisotropy-profiles). The detected SBL depth, mostly deviates from the jet maximum height or the top of the near-surface inversion. The flat terrain formulations for the SBL height correlate well with the detected top of the SBL if instead of background stratification, near-surface stratification is used in their formulations, however, they mostly largely overestimate the SBL height. The difference to flat-terrain SBL is also shown through the dependence of size of the dominant eddy with height. In katabatic flows the eddy size is semi-constant with height throughout the SBL, whereas in flat terrain eddy size varies significantly with height.

The successive stages of nocturnal atmospheric structure inside a small isolated basin are investigated when a katabatically driven flow on an adjacent tilted plain advects cold air over the basin rim. Data came from Arizona’s Meteor Crater during intensive observing period 4 of the Second Meteor Crater Experiment (METCRAX II) when a mesoscale flow above the plain was superimposed on the katabatic flow leading to a flow acceleration and then deceleration over the course of the night. Following an overflow-initiation phase, the basin atmosphere over the upwind inner sidewall progressed through three stages as the katabatic flow accelerated: 1) a cold-air-intrusion phase in which the overflowing cold air accelerated down the upwind inner sidewall, 2) a bifurcation phase in which the katabatic stable layer lifted over the rim included both a nonnegatively buoyant upper layer that flowed horizontally over the basin and a negatively buoyant lower layer (the cold-air intrusion) that continued on the slope below to create a hydraulic jump at the foot of the sidewall, and 3) a final warm-air-intrusion phase in which shear instability in the upper overflowing layer produced a lee wave that brought warm air from the elevated residual layer downward into the basin. Strong winds during the third phase penetrated to the basin floor, stirring the preexisting, intensely stable, cold pool. Later in the night a wind direction change aloft decelerated the katabatic wind and the atmosphere progressed back through the bifurcation and cold-air-intrusion phases. A conceptual diagram illustrates the first four evolutionary phases.

The interactions between a katabatic flow on a plain and a circular basin cut into the plain and surrounded by an elevated rim were examined during a 5-h steady-state period during the Second Meteor Crater Experiment (METCRAX II) to explain observed disturbances to the nocturnal basin atmosphere. The approaching katabatic flow split horizontally around Arizona’s Meteor Crater below a dividing streamline while, above the dividing streamline, an ~50-m-deep stable layer on the plain was carried over the 30–50-m rim of the basin. A flow bifurcation occurred over or just upwind of the rim, with the lowest portion of the stable layer having negative buoyancy relative to the air within the crater pouring continuously over the crater’s upwind rim and accelerating down the inner sidewall. The cold air intrusion was deepest and coldest over the direct upwind crater rim. Cold air penetration depths varied around the inner sidewall depending on the temperature deficit of the inflow relative to the ambient environment inside the crater. A shallow but extremely stable cold pool on the crater floor could not generally be penetrated by the inflow and a hydraulic jump–like feature formed on the lower sidewall as the flow approached the cold pool. The upper nonnegatively buoyant portion of the stable layer was carried horizontally over the crater, forming a neutrally stratified, low–wind speed cavity or wake in the lee of the upwind rim that extended downward into the crater over the upwind sidewall.

The Salt Lake Valley experiences severe fine particulate matter pollution episodes in winter during persistent cold-air pools (PCAPs). We employ measurements throughout an entire winter from different elevations to examine the chemical and dynamical processes driving these episodes. Whereas primary pollutants such as NOx and CO were enhanced twofold during PCAPs, O3 concentrations were approximately threefold lower. Atmospheric composition varies strongly with altitude within a PCAP at night with lower NOx and higher oxidants (O3) and oxidized reactive nitrogen (N2O5) aloft. We present observations of N2O5 during PCAPs that provide evidence for its role in cold-pool nitrate formation. Our observations suggest that nighttime and early morning chemistry in the upper levels of a PCAP plays an important role in aerosol nitrate formation. Subsequent daytime mixing enhances surface PM2.5 by dispersing the aerosol throughout the PCAP. As pollutants accumulate and deplete oxidants, nitrate chemistry becomes less ...

Semi-idealized model simulations are made of the nocturnal cold-air pool development in the approximately 1-km wide and 100–200-m deep Grunloch basin, Austria. The simulations show qualitatively good agreement with vertical temperature and wind profiles and surface measurements collected during a meteorological field expedition. A two-layer stable atmosphere forms in the basin, with a very strong inversion in the lowest part, below the approximate height of the lowest gap in the surrounding orography. The upper part of the stable layer is less strongly stratified and extends to the approximate height of the second-lowest gap. The basin atmosphere cools most strongly during the first few hours of the night, after which temperatures decrease only slowly. An outflow of air forms through the lowest gap in the surrounding orography. The outflow connects with a weak inflow of air through a gap on the opposite sidewall, forming a vertically and horizontally confined jet over the basin. Basin cooling shows strong sensitivity to surface-layer characteristics, highlighting the large impact of variations in vegetation and soil cover on cold-air pool development, as well as the importance of surface-layer parametrization in numerical simulations of cold-air-pool development.

A comprehensive analysis of the turbulence structure of relatively deep midlatitude katabatic flows (with jet maxima between 20 and 50 m) developing over a gentle (1°) mesoscale slope with a long fetch upstream of the Meteor Crater in Arizona is presented. The turbulence structure of flow below the katabatic jet maximum shows many similarities with the turbulence structure of shallower katabatic flows, with decreasing turbulence fluxes with height and almost constant turbulent Prandtl number. Still stark differences occur above the jet maximum where turbulence is suppressed by strong stability, is anisotropic and there is a large sub‐mesoscale contribution to the flux. Detecting the stable boundary‐layer top depends on the method used (flux‐ vs. anisotropy‐profiles) but both methods are highly correlated. The top of the stable boundary layer, however, mostly deviates from the jet maximum height or the top of the near‐surface inversion. The flat‐terrain formulations for the boundary‐layer height correlate well with the detected top of the stable boundary layer if the near‐surface and not the background stratification is used in their formulations; however, they mostly largely overestimate this boundary‐layer height. The difference from flat‐terrain boundary layers is also shown through the dependence of size of the dominant eddy with height. In katabatic flows the eddy size is semi‐constant with height throughout the stable boundary‐layer depth, whereas in flat terrain, eddy size varies significantly with height. Flux‐gradient and flux‐variance relationships show that turbulence data from different stable boundary‐layer scaling regimes collapse on top of each other showing that the dominant dependence is not on the scaling regime but on the local stability., Persistent relatively deep katabatic flows develop over a shallow mesoscale slope outside the Meteor Crater, Arizona. Their turbulent structure deviates from the structure of shallow katabatic flows in that the small‐scale turbulence is strongly attenuated already at heights below the jet maximum. The height of the stable katabatic boundary layer is significantly lower than over flat terrain for the same forcing. The change of turbulence anisotropy below and above the boundary layer provides a new diagnostic of boundary‐layer height.

The nearly circular Meteor Crater, Arizona, is located on an extensive, slightly sloping plain, above which a south-westerly katabatic flow forms during undisturbed, clear-sky nights. For the katabatic flow over the upstream crater rim, the resulting flow regime in the lee depends on the upstream wind speed. For a shallow katabatic flow with a wind-speed maximum of about 5 m s $$^{-1}$$ or less at a height of about 20 m above the ground, the flow decelerates as it approaches the crater. Cold-air intrusions form, that is, cold air spills over the crater rim and runs down the inner south-west sidewall. For a deep katabatic flow with a wind-speed maximum located above the 50-m high measurement tower and comparatively higher wind speeds, the flow accelerates towards the crater. The flow separates in the immediate lee of the crater rim, forming a wake over the south-west crater sidewall. The wake can either be small, affecting only the upper part of the sidewall, or large, affecting the entire crater sidewall or even the crater floor. When flow separation occurs, the wake region over the crater sidewall is characterized by low wind speeds and potentially a return circulation near the surface. Particularly for large wakes, stability in the crater atmosphere is reduced and relatively high wind speeds occur at the crater floor, which is otherwise submerged in a strong surface-based inversion. Turbulent kinetic energy at the crater sidewall is typically higher during cold-air intrusions than is the case during flow separation, but high values can occur at the floor when a large wake forms.

Idealized two-dimensional model simulations are performed to study the frequent nocturnal occurrence of downslope-windstorm-type flows in Arizona’s Meteor Crater. The model topography is a simplified representation of the Meteor Crater and its surroundings, with an approximately 1° mesoscale slope upstream and downstream of the crater basin. A strong surface-based inversion and a katabatic flow develop above the mesoscale slope as a result of radiational cooling. The temperature and flow profiles are evaluated against observations over low-angle slopes from two field campaigns, showing that the model’s turbulence parameterization has a strong impact on the near-surface conditions. The interaction of the katabatic flow with the basin topography leads to the formation of waves and hydraulic jumps over the basin. The simplified two-dimensional simulations show good qualitative agreement with observations of downslope-windstorm-type flows from the Meteor Crater. The sensitivity of the flow solution over the basin to basin depth, basin width, and background wind speed is investigated. The resulting flow regimes include a sweeping of the basin atmosphere, a wake over the upstream crater sidewall, waves over the basin with one or two wave crests, and a hydraulic jump. The regimes are discussed in the context of stratified flow over mountains.

The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age = 54 years, time immunosuppressed = 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio = 1.61, 95% confidence interval = [1.07, 2.43]), reported past skin cancer (prevalence ratio =3.39, 95% confidence interval = [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio = 1.76, 95% confidence interval = [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services.

The second Meteor Crater Experiment (METCRAX II) was conducted in October 2013 at Arizona’s Meteor Crater. The experiment was designed to investigate nighttime downslope windstorm−type flows that form regularly above the inner southwest sidewall of the 1.2-km diameter crater as a southwesterly mesoscale katabatic flow cascades over the crater rim. The objective of METCRAX II is to determine the causes of these strong, intermittent, and turbulent inflows that bring warm-air intrusions into the southwest part of the crater. This article provides an overview of the scientific goals of the experiment; summarizes the measurements, the crater topography, and the synoptic meteorology of the study period; and presents initial analysis results.

Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10 to 0.24; P = 4.09 × 10(−06)) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P = 7.87 × 10(−04)), and highlight seven genes including PIEZO1, TRAPPC2L, and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.

Because of long-term immunosuppressive therapy, organ transplant recipients experience significantly elevated skin cancer risk1 and mortality.2 Because of increasing rates of transplantation and improved survival among organ transplant recipients, primary skin cancer prevention is essential for organ transplant recipients to reduce their skin cancer burden. Elsewhere we reported the sun protection behaviors among a subset of organ transplant recipients who were at especially high risk of skin cancer because of a history of actinic skin lesions. We found that approximately 50% of the study participants regularly practiced multiple sun protection measures.3 It has been shown elsewhere that specific educational interventions can improve the use of sun protection measures among organ transplant recipients.4 Here we report a significant increase in the number of organ transplant recipients who practiced multiple sun protection behaviors after participation in a skin cancer research study for at least 1 year without any specific educational intervention.

Cold air pools (CAPs) are stagnant stable air masses that form in valleys and basins in the winter. Low wintertime insolation limits convective mixing, such that pollutant concentrations can build up within the CAP when pollutant sources are present. In the western United States, wintertime CAPs often persist for days or weeks. Atmospheric models do not adequately capture the strength and evolution of CAPs. This is in part due to the limited availability of data quantifying the local turbulence during the formation, maintenance, and destruction of persistent CAPs. This paper presents observational data to quantify the turbulent mixing during two CAP episodes in Utah's Salt Lake Valley during February of 2004. Particulate matter (PM) concentration data and turbulence measurements for CAP and non-CAP time periods indicate that two distinct types of mixing scenarios occur depending on whether the CAP is dry or cloudy. Where cloudy, CAPs have enhanced vertical mixing due to top-down convection from the cloud layer. A comparison between the heat and momentum fluxes during 5 days of a dry CAP episode in February to those of an equivalent 5 day time period in March with no CAP indicates that the average turbulent kinetic energy during the CAP was suppressed by approximately 80%.

Observations were taken on an east-facing sidewall at the foot of a desert mountain that borders a large valley, as part of the Mountain Terrain Atmospheric Modeling and Observations (MATERHORN) field program at Dugway Proving Ground in Utah. A case study of nocturnal boundary layer development is presented for a night in mid-May when tethered-balloon measurements were taken to supplement other MATERHORN field measurements. The boundary layer development over the slope could be divided into three distinct phases during this night: 1) The evening transition from daytime upslope/up-valley winds to nighttime downslope winds was governed by the propagation of the shadow front. Because of the combination of complex topography at the site and the solar angle at this time of year, the shadow moved down the sidewall from approximately northwest to southeast, with the flow transition closely following the shadow front. 2) The flow transition was followed by a 3–4-h period of almost steady-state boundary layer conditions, with a shallow slope-parallel surface inversion and a pronounced downslope flow with a jet maximum located within the surface-based inversion. The shallow slope boundary layer was very sensitive to ambient flows, resulting in several small disturbances. 3) After approximately 2300 mountain standard time, the inversion that had formed over the adjacent valley repeatedly sloshed up the mountain sidewall, disturbing local downslope flows and causing rapid temperature drops.

The vernal equinox total solar eclipse of 20 March 2015 produced a maximum occultation of 65.8 to 70.1 % over Switzerland during the morning hours (09:22 to 11:48 CET). Skies were generally clear over the Swiss Alps due to a persistent high-pressure band between the UK and Russia associated with a rather weak pressure gradient over the continent. To assess the effects of penumbral shading on near-surface meteorology across Switzerland, air temperature data measured at 10-minute intervals at 184 MeteoSwiss weather stations that reported air temperature at 10-minute intervals were used. Wind speed and direction data were available from 165 of these stations. Additionally, six Swiss FluxNet eddy covariance flux (ECF) sites provided turbulent measurements at 20 Hz resolution. During maximum occultation the temperature drop was up to 5.8 K at a mountain site where cold air can pool in the topographic depression of the weather station. The bootstrapped average of the maximum temperature drops of all 184 MeteoSwiss sites during the solar eclipse was 1.51 ± 0.02 K (mean ± SE). A detailed comparison with literature values since 1834 showed a temperature decrease by 2.6 ± 1.7 K (average of all reports) with extreme values up to 11 K. On fair weather days under weak larger scale pressure gradients, local thermo-topographic wind systems develop that are driven by small-scale pressure and temperature gradients. At one ECF site, the penumbral shading delayed the morning transition from down-valley to up-valley wind conditions, and at another site, it prevented this transition from occurring at all. Data from the 165 MeteoSwiss sites measuring wind direction did not show a consistent pattern of wind direction response to the passing of the penumbral shadow. These results suggest that the local topographic setting had an important influence on the temperature drop and the wind flow patterns during the eclipse. Still, results tend to lend support to a recent theory that the anticyclonic cold-air outflow from the center of the eclipse only extends ≈ 1600 km outwards, with cyclonic flow beyond that distance. This contrasts with an earlier theory that the anticyclonic outflow should reach as far as ≈ 2400 km from the center of the eclipse, which would have included all of Switzerland during the 2015 eclipse. Nevertheless, a significant cyclonic effect of the passing penumbral shadow was found in the elevation range ≈ 1700–2700 m a.s.l., but not at lower elevations of the Swiss Plateau. Thus, measurable effects of penumbral shading on the local wind system could be even found at ≈ 2000 km from the path of the eclipse (that is, Switzerland during the 2015 eclipse).

The Salt Lake Valley experiences severe fine particulate matter pollution episodes in winter during persistent cold-air pools (PCAPs). We employ measurements throughout an entire winter from different elevations to examine the chemical and dynamical processes driving these episodes. Whereas primary pollutants such as NO

Pseudovertical temperature “soundings” from lines of inexpensive temperature sensors on the sidewalls of Utah’s Salt Lake valley are compared with contemporaneous radiosonde soundings from the north, open end of the valley. Morning [0415 mountain standard time (MST)] soundings are colder, and afternoon (1615 MST) soundings are warmer than radiosonde soundings because of warm and cold boundary layers that form over the slopes. Cross-valley temperature differences occur between east- and west-facing sidewalls because of differing insolation. Differences in vertically averaged pseudovertical and radiosonde temperatures are generally within 1°C, with a standard deviation of 2°–3°C. The pseudovertical soundings are especially good proxies for radiosondes in winter. The sounding comparisons identified along-valley differences in temperature, inversion depth, and lapse rate that have led to hypotheses concerning their causes, to be evaluated with future research. The low cost and much better time resolution of the pseudovertical soundings suggest that such lines will be a useful supplement to valley radiosondes and will have significant operational advantages if available in real time. Lines of surface-based sensors will prove useful in identifying intravalley meteorological differences and may be used to estimate free-air temperature structure in other valleys where radiosondes are unavailable.

Critical meteorological factors affecting daily particulate concentrations during winter for Utah's urbanized Salt Lake Valley are examined on the basis of forty years of data. In a typical winter, the National Ambient Air Quality Standard for particulate matter with aerodynamic diameter less than 2.5 microns (PM2.5) is exceeded during 6 multi-day events comprising 18 winter days. Multi-day episodes of high stability produce these events, as synoptic-scale high-pressure ridges transit across Utah. The valley heat deficit, a bulk measure of atmospheric stability, exhibits large winter-to-winter variations that are highly related to similar variations in PM2.5. While control strategies have led to downward trends in concentrations for some primary pollutants, no long-term trends in valley heat deficit are evident over the 40 years. PM2.5 concentrations rise gradually over a period of days after a heat deficit threshold is exceeded as the air within the valley becomes decoupled from generally stronger winds aloft. Concentrations climb at a typical rate of about 10 μg m−3 d−1 over a four-day period to about 60 μg m−3 during these episodes. During episodes when PM2.5 concentrations exceed 35 μg m−3, the atmospheric column in the valley is characterized by: temperature below 0 °C; relative humidity in excess of 50%; and light wind speeds. PM2.5 concentrations in excess of 35 μg m−3 are four times more likely when the valley is snow covered than when it is not. A stepwise multiple linear regression based upon selected meteorological variables is used to estimate daily values of PM2.5 during two independent winters. The correlation between observed and estimated PM2.5 for these winters reaches 0.81.

Background Body mass index is associated with the risk of Barrett's oesophagus (BO). It is uncertain whether this is related to total body fat or other factors that correlate with body mass index. We aimed to quantify the association between total body fat (measured by bioelectrical impedance) and risk of BO and examine if this association was modified by gastro-oesophageal reflux (GOR) and abdominal obesity. Methods In 2007–2009, we surveyed 235 cases (69% Males, Mean age 62.1 years) and 244 age and sex matched population controls from a population based case–control study of BO. We conducted structured interviews, standard anthropometry and bioimpedance analysis of total body fat. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression analysis. Results There was a significantly increased risk of BO among those in the highest tertile of total body fat weight (OR 2.01; 95%CI 1.26–3.21) and total body fat percentage (OR 1.86; 95%CI 1.10–3.15). These risks were largely attenuated after adjustment for GOR and waist circumference. There was a significantly increased risk of BO among those in the highest tertile of waist circumference (OR 2.21; 95%CI 1.39–3.51) and this was minimally attenuated after adjustment for total body fat and moderately attenuated after adjustment for GOR. Conclusions Total body fat is associated with an increased risk of BO but this appears to be mediated via both abdominal obesity and GOR. These findings provide evidence that abdominal obesity is more important than total body fat in the development of BO.

The late afternoon upslope–downslope flow transition on the west inner sidewall of Arizona’s Meteor Crater, visualized by photographs of smoke dispersion, is investigated for 20 October 2006 using surface radiative and energy budget data and mean and turbulent flow profiles from three towers, two at different distances up the slope and one on the basin floor. The bowl-shaped crater allows the development of the upslope–downslope flow transition with minimal influence from larger-scale motions from outside and avoiding the upvalley–downvalley flow interactions typical of valleys. The slow downslope propagation of the shadow from the west rim causes a change in the surface radiation budget and the consequent loss of heat from the shallow atmospheric layer above the western slope at a time when the sun still heats the crater floor and the inner east sidewall. The onset of the katabatic flow is visualized by the dispersion of the smoke, and the onset occurs at the same time at the two slope towers. The katabatic flow arrives later at the crater floor, cooling the air and contributing to the stabilization of a shallow but strong inversion layer there. A wavelet analysis indicates that the initial upslope current is driven by crater-size scales, whereas the later downslope flow is influenced by the thermal gradient between opposing sidewalls generated by their different cooling rates. A comparison with other days suggests that the timing of the transition is also influenced by the presence of convective eddies in addition to the local energy balance.

Rime mushrooms, commonly called ice mushrooms, are large bulbous or mushroom-shaped accretions of hard rime that build up on the upwind side of mountain summits and ridges and on windward rock faces. This paper reviews the characteristics of rime mushrooms; the topographical, geographical, and meteorological conditions under which they form; and the significant challenge they pose to climbers. Photographs and descriptions from Southern Patagonia, where rime mushrooms are well known, illustrate the phenomenon.

The physical mechanisms responsible for the formation of a thermally driven cross-basin circulation in a basin with asymmetric heating of opposite mountain sidewalls are investigated. A large-eddy simulation is performed with the Weather Research and Forecasting model for an idealized basin based on the topography of Arizona's Meteor Crater. The individual components of the horizontal momentum and thermodynamic balance equations are analyzed to determine their respective contributions in forcing the cross-basin circulation. A cross-basin pressure gradient, with higher pressure on the less irradiated sidewall, leads to the development of a cross-basin flow near the basin floor. A weak opposing return flow develops above this cross-basin flow as a result of a reversed cross-basin pressure gradient. The reversed cross-basin pressure gradient is caused by cold-air advection by upslope winds in the stable morning atmosphere on the sunlit sidewall and warm-air advection by downslope winds on the still shaded sidewall, as this reverses the cross-basin temperature gradient, producing a higher temperature on the less sunlit sidewall.

Thermally driven valley-exit jets were investigated at Utah’s Weber Canyon, a main tributary of the Great Salt Lake basin. An intensive measurement campaign during July–September 2010 supplemented longer-term measurements to characterize the wind and temperature structure in the vicinity of the canyon exit. Exit jets at Weber Canyon are most frequent in late summer or early fall. Strong low-level-wind jets formed at the canyon exit on 75 of 90 nights (83%) during the measurement campaign, with the best-developed winds forming during synoptically undisturbed, clear-sky periods. Winds inside the canyon consisted of a weak down-valley flow layer that occupied most of the 1000-m depth of the canyon. The flow was observed to descend, thin, and accelerate at the valley exit, producing winds that were typically 2.5 times as strong but much more shallow than those inside the canyon. Maximum nighttime jet-axis wind speeds of 15–20 m s−1 are typically found about 80–120 m above the ground at the canyon exit on clear undisturbed nights in the late summer and fall. The jets form 1–3 h after sunset, approach a near-steady state during the late night, and continue until 5–6 h after sunrise, although slowly losing speed after sunrise. The jet is a local modification at the canyon exit of the thermally driven down-valley flow. Its continuation after sunrise is thought to be caused by the nighttime buildup and persistence of a cold-air pool in the Morgan Basin at the east end of the canyon. The potential for utilizing the exit jet for wind power generation is discussed.

The Persistent Cold-Air Pool Study (PCAPS) was conducted in Utah's Salt Lake valley from 1 December 2010 to 7 February 2011. The field campaign's primary goal was to improve understanding of the physical processes governing the evolution of multiday cold-air pools (CAPs) that are common in mountain basins during the winter. Meteorological instrumentation deployed throughout the Salt Lake valley provided observations of the processes contributing to the formation, maintenance, and destruction of 10 persistent CAP episodes. The close proximity of PCAPS field sites to residences and the University of Utah campus allowed many undergraduate and graduate students to participate in the study. Ongoing research, supported by the National Science Foundation, is using the PCAPS dataset to examine CAP evolution. Preliminary analyses reveal that variations in CAP thermodynamic structure are attributable to a multitude of physical processes affecting local static stability: for example, synoptic-scale processes impact changes in temperatures and cloudiness aloft while variations in boundary layer forcing modulate the lower levels of CAPs. During episodes of strong winds, complex interactions between the synoptic and mesoscale f lows, local thermodynamic structure, and terrain lead to both partial and complete removal of CAPs. In addition, the strength and duration of CAP events affect the local concentrations of pollutants such as PM2.5.