The effect of lockdown on melanoma stage in Devon, UK.

We performed a prospective analysis of Breslow thickness in melanoma before the COVID-19 pandemic and after. It shows that there is a statistically significant increase in melanoma thickness, and ultimately melanoma staging, since the pandemic began.

Clinicopathological characteristics of individuals with coexisting melanoma and chronic lymphocytic leukaemia: a multicentre cohort study.

BACKGROUND: Individuals with a prior diagnosis of chronic lymphocytic leukaemia (CLL) have a higher risk of developing melanoma and exhibit poorer outcomes than patients without CLL. However, there are limited data reporting the clinicopathological features of melanoma diagnosed in patients with CLL. AIMS: To review clinicopathological characteristics of patients with coexisting diagnoses of melanoma and CLL. METHODS: A retrospective review was undertaken for patients with coexisting diagnoses of melanoma and CLL between 2005 and 2015 in 11 centres in the UK and Ireland. RESULTS: Overall, 46 cutaneous melanomas identified in 45 patients were included. In 28 (62.2%) patients, melanoma was diagnosed after an existing diagnosis of CLL. In this group, mean Breslow thickness was 2.7 mm (range 0.2-25 mm). Ten patients (35.7%) developed locoregional recurrence and 8 (28.6%) developed distant metastases. Melanoma-specific mortality was 5 of 28 (17.9%) and all-cause mortality was 13 of 28 (46.4%). In 17 patients, melanoma was diagnosed before CLL. In this group, mean BT was 2.9 mm (range 0.4-14 mm); five patients (29.4%) developed locoregional recurrence and three (17.6%) developed distant metastases. Melanoma-specific mortality was 1 of 17 (5.8%) and all-cause mortality was 5 of 17 (29.4%) in this group. CONCLUSIONS: To our knowledge, this is the first and largest cohort study to report clinicopathological data of coexisting melanoma and CLL in the UK and Ireland. Although the thickness of primary melanoma was not different before or after a CLL diagnosis, melanoma recurrence and melanoma-specific mortality appear to be more common in patients with a prior diagnosis of CLL.

Screening for cystic fibrosis in New York State: considerations for algorithm improvements.

Newborn screening for cystic fibrosis (CF), a chronic progressive disease affecting mucus viscosity, has been beneficial in both improving life expectancy and the quality of life for individuals with CF. In New York State from 2007 to 2012 screening for CF involved measuring immunoreactive trypsinogen (IRT) levels in dried blood spots from newborns using the IMMUCHEM(™) Blood Spot Trypsin-MW ELISA kit. Any specimen in the top 5% IRT level underwent DNA analysis using the InPlex(®) CF Molecular Test. Of the 1.48 million newborns screened during the 6-year time period, 7631 babies were referred for follow-up. CF was confirmed in 251 cases, and 94 cases were diagnosed with CF transmembrane conductance regulated-related metabolic syndrome or possible CF. Nine reports of false negatives were made to the program. Variation in daily average IRT was observed depending on the season (4-6 ng/ml) and kit lot (<3 ng/ml), supporting the use of a floating cutoff. The screening method had a sensitivity of 96.5%, specificity of 99.6%, positive predictive value of 4.5%, and negative predictive value of 99.5%. CONCLUSION: Considerations for CF screening algorithms should include IRT variations resulting from age at specimen collection, sex, race/ethnicity, season, and manufacturer kit lots. WHAT IS KNOWN: Measuring IRT level in dried blood spots is the first-tier screen for CF. Current algorithms for CF screening lead to substantial false-positive referral rates. WHAT IS NEW: IRT values were affected by age of infant when specimen is collected, race/ethnicity and sex of infant, and changes in seasons and manufacturer kit lots The prevalence of CF in NYS is 1 in 4200 with the highest prevalence in White infants (1 in 2600) and the lowest in Black infants (1 in 15,400).

Evaluation of the Readability of Dermatological Postoperative Patient Information Leaflets Across England.

BACKGROUND: Postoperative patient information leaflets (PILs) provide important guidance to patients after skin surgery. Readability is a method of evaluating information for text comprehension. The recommended level for PIL readability is US grade ≤6. OBJECTIVE: To evaluate the readability of public English dermatological postoperative PILs. MATERIALS AND METHODS: All dermatology departments in England were requested to provide their postoperative PILs. Patient information leaflets were evaluated using Readability Studio (Oleander Software, Vandalia, OH). Two preselected parameters were also noted: whether the PIL was doctor or nurse-written, and whether the PIL was Information Standard hallmarked. RESULTS: Eighty-five of one hundred thirty (65.4%) of PILs were evaluated. Only 29.4% of the PILs were grade level ≤6 with Flesch-Kincaid. The mean readability levels were 7.8 for Flesch-Kincaid, 67 for Flesch reading ease, 10.5 for Simple Measure of Gobbledygook (SMOG), 9.4 for Gunning-Fog, 8 for Fry, and 9.8 for FORCAST. No instruments demonstrated a significant difference between doctor (6) and nurse-written (7) PILs. Two instruments found that the 3 Information Standard hallmarked PILs had a higher (harder) readability than ordinary PILs (n = 82) (Gunning-Fog, p = .029*; SMOG p = .049*). CONCLUSION: Most English postoperative dermatological PILs' readability levels exceed recommendations (US grade ≤6). Departmental PILs should be reviewed to ensure that they are comprehensible to their patients.

Global conservation status of sponges.

Sponges are important for maintaining ecosystem function and integrity of marine and freshwater benthic communities worldwide. Despite this, there has been no assessment of their current global conservation status. We assessed their status, accounting for the distribution of research effort; patterns of temporal variation in sponge populations and assemblages; the number of sponges on threatened species lists; and the impact of environmental pressures. Sponge research effort has been variable; marine sponges in the northeastern Atlantic and Mediterranean and freshwater sponges in Europe and North America have received the most attention. Although sponge abundance has increased in some locations since 1990, these were typically on coral reefs, in response to declines in other benthic organisms, and restricted to a few species. Few data were available on temporal trends in freshwater sponge abundance. Despite over 8500 described sponge species, only 20 are on threatened species lists, and all are marine species from the northeastern Atlantic and Mediterranean. Of the 202 studies identified, the effects of temperature, suspended sediment, substratum loss, and microbial pathogens have been studied the most intensively for marine sponges, although responses appear to be variable. There were 20 studies examining environmental impacts on freshwater sponges, and most of these were on temperature and heavy metal contamination. We found that most sponges do not appear to be threatened globally. However, little information is available for most species and more data are needed on the impacts of anthropogenic-related pressures. This is a critical information gap in understanding sponge conservation status.

Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects.

BACKGROUND: Neural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population. METHODS: Replication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS. RESULTS: Of the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans. CONCLUSIONS: We report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis.

Bone metabolism during strict head-down tilt bed rest and exposure to elevated levels of ambient CO2.

Astronauts on the International Space Station are exposed to levels of atmospheric carbon dioxide (CO2) above typical terrestrial levels. We explored the possibility that increased levels of ambient CO2 further stimulate bone resorption during bed rest. We report here data from 2 ground-based spaceflight analog studies in which 12 male and 7 female subjects were placed in a strict 6° head-down tilt (HDT) position for either 30 days at 0.5% ambient CO2 or 60 days with nominal environmental exposure to CO2. Bone mineral density (BMD) and bone mineral content (BMC) were determined using dual-energy X-ray absorptiometry (DXA). Blood and urine were collected before and after HDT for biochemical analysis. No change was detected in either BMD or BMC, as expected given the study duration. Bone resorption markers increased after bed rest as expected; however, elevated CO2 had no additive effect. Elevated CO2 did not affect concentrations of minerals in serum and urine. Serum parathyroid hormone and 1,25-dihydroxyvitamin D were both reduced after bed rest, likely secondary to calcium efflux from bone. In summary, exposure to 0.5% CO2 for 30 days did not exacerbate the typical bone resorption response observed after HDT bed rest. Furthermore, results from these strict HDT studies were similar to data from previous bed rest studies, confirming that strict 30-60 days of HDT can be used to evaluate changes in bone metabolism. This is valuable in the continuing effort to develop and refine efficacious countermeasure protocols to mitigate bone loss during spaceflight in low-Earth orbit and beyond.

Association of Promoting Housing Affordability and Stability With Improved Health Outcomes: A Systematic Review.

Importance: Housing insecurity-that is, difficulty with housing affordability and stability-is prevalent and results in increased risk for both homelessness and poor health. However, whether interventions that prevent housing insecurity upstream of homelessness improve health remains uncertain. Objective: To review evidence characterizing associations of primary prevention strategies for housing insecurity with adult physical health, mental health, health-related behaviors, health care use, and health care access. Evidence Review: Pairs of independent reviewers systematically searched PubMed, Web of Science, EconLit, and the Social Interventions Research and Evaluation Network for quantitative studies published from 2005 to 2021 that evaluated interventions intended to directly improve housing affordability and/or stability either by supporting at-risk households (targeted primary prevention) or by enhancing community-level housing supply and affordability in partnership with the health sector (structural primary prevention). Risk of bias was appraised using validated tools, and the evidence was synthesized using modified Grading of Recommendations Assessment, Development, and Evaluation criteria. Findings: A total of 26 articles describing 3 randomized trials and 20 observational studies (16 longitudinal designs and 4 cross-sectional quasi-waiting list control designs) were included. Existing interventions have focused primarily on mitigating housing insecurity for the most vulnerable individuals rather than preventing housing insecurity outright. Moderate-certainty evidence was found that eviction moratoriums were associated with reduced COVID-19 cases and deaths. Certainty of evidence was low or very low for health associations of other targeted primary prevention interventions, including emergency rent assistance, legal assistance with waiting list priority for public housing, long-term rent subsidies, and homeownership assistance. No studies evaluated health system-partnered structural primary prevention strategies. Conclusions and Relevance: This systematic review found mixed and mostly low-certainty evidence that interventions that promote housing affordability and stability were associated with improved adult health outcomes. Existing interventions may need to be paired with other efforts to address the structural determinants of health. As health care systems and insurers respond to increasing opportunities to invest in housing as a determinant of health, further research is needed to clarify where along the housing insecurity pathway interventions should focus for the most effective and equitable health impact.

'Relaxers' damage hair: evidence from amino acid analysis.

BACKGROUND: 'Relaxers' are used by more than two thirds of African females to straighten hair, with easy grooming and increased length often cited as reasons. A recent study reported relaxed hair lengths much shorter than expected, suggesting increased fragility; the potential for scalp inflammation and scarring alopecia remains unclear. OBJECTIVE: To investigate the biochemical effects of 'relaxers' on hair. METHODS: With informed consent, included participants represented 3 groups: natural hair, asymptomatic relaxed hair, and symptomatic (brittle) relaxed hair. Biochemical analysis was performed by using a Biochrom 30 amino acid analyzer. Differences in amino acid levels were assessed using either Wilcoxon rank sum test or matched-pairs signed-rank test. RESULTS: There was a decrease in cystine, citrulline, and arginine; however, an increase in glutamine was found in all relaxed compared to natural hair. Cystine levels (milligram per gram amino acid nitrogen) were similar in natural proximal and distal hair: 14 mg/g (range, 4-15 mg/g) versus 14 mg/g (range, 12-15 mg/g); P = .139. In asymptomatic relaxed hair, cystine levels were higher in less frequently relaxed samples proximal to scalp: 7.5 mg/g (5.6-12) versus 3.3 mg/g (1.3-9.2); P = .005. Cystine levels in distal asymptomatic relaxed and symptomatic relaxed hair were similar to each other and to those in the genetic hair fragility disease trichothiodystrophy. LIMITATIONS: It was not possible to analyze lye and no-lye 'relaxers' separately. CONCLUSIONS: 'Relaxers' are associated with reduced cystine consistent with fragile damaged hair. A decrease in citrulline and glutamine has been associated with inflammation; prospective studies are needed to investigate whether or how 'relaxers' induce inflammation.

Interocean patterns in shallow water sponge assemblage structure and function.

Sponges are a major component of benthic ecosystems across the world and fulfil a number of important functional roles. However, despite their importance, there have been few attempts to compare sponge assemblage structure and ecological functions across large spatial scales. In this review, we examine commonalities and differences between shallow water (<100 m) sponges at bioregional (15 bioregions) and macroregional (tropical, Mediterranean, temperate, and polar) scales, to provide a more comprehensive understanding of sponge ecology. Patterns of sponge abundance (based on density and area occupied) were highly variable, with an average benthic cover between ~1 and 30%. Sponges were generally found to occupy more space (percentage cover) in the Mediterranean and polar macroregions, compared to temperate and tropical macroregions, although sponge densities (sponges m-2 ) were highest in temperate bioregions. Mean species richness standardised by sampling area was similar across all bioregions, except for a few locations that supported very high small-scale biodiversity concentrations. Encrusting growth forms were generally the dominant sponge morphology, with the exception of the Tropical West Atlantic, where upright forms dominated. Annelids and Arthropods were the most commonly reported macrofauna associated with sponges across bioregions. With respect to reproduction, there were no patterns in gametic development (hermaphroditism versus gonochorism), although temperate, tropical, and polar macroregions had an increasingly higher percentage of viviparous species, respectively, with viviparity being the sole gamete development mechanism reported for polar sponges to date. Seasonal reproductive timing was the most common in all bioregions, but continuous timing was more common in the Mediterranean and tropical bioregions compared to polar and temperate bioregions. We found little variation across bioregions in larval size, and the dominant larval type across the globe was parenchymella. No pattens among bioregions were found in the limited information available for standardised respiration and pumping rates. Many organisms were found to predate sponges, with the abundance of sponge predators being higher in tropical systems. While there is some evidence to support a higher overall proportion of phototrophic species in the Tropical Austalian bioregion compared to the Western Atlantic, both also have large numbers of heterotrophic species. Sponges are important spatial competitors across all bioregions, most commonly being reported to interact with anthozoans and algae. Even though the available information was limited for many bioregions, our analyses demonstrate some differences in sponge traits and functions among bioregions, and among macroregions. However, we also identified similarities in sponge assemblage structure and function at global scales, likely reflecting a combination of regional- and local-scale biological and physical processes affecting sponge assemblages, along with common ancestry. Finally, we used our analyses to highlight geographic bias in past sponge research, and identify gaps in our understanding of sponge ecology globally. By so doing, we identified key areas for future research on sponge ecology. We hope that our study will help sponge researchers to consider bioregion-specific features of sponge assemblages and key sponge-mediated ecological processes from a global perspective.

Author Correction: Growth and longevity in giant barrel sponges: Redwoods of the reef or Pines in the Indo-Pacific?

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Assessment of Accuracy of an Artificial Intelligence Algorithm to Detect Melanoma in Images of Skin Lesions.

Importance: A high proportion of suspicious pigmented skin lesions referred for investigation are benign. Techniques to improve the accuracy of melanoma diagnoses throughout the patient pathway are needed to reduce the pressure on secondary care and pathology services. Objective: To determine the accuracy of an artificial intelligence algorithm in identifying melanoma in dermoscopic images of lesions taken with smartphone and digital single-lens reflex (DSLR) cameras. Design, Setting, and Participants: This prospective, multicenter, single-arm, masked diagnostic trial took place in dermatology and plastic surgery clinics in 7 UK hospitals. Dermoscopic images of suspicious and control skin lesions from 514 patients with at least 1 suspicious pigmented skin lesion scheduled for biopsy were captured on 3 different cameras. Data were collected from January 2017 to July 2018. Clinicians and the Deep Ensemble for Recognition of Malignancy, a deterministic artificial intelligence algorithm trained to identify melanoma in dermoscopic images of pigmented skin lesions using deep learning techniques, assessed the likelihood of melanoma. Initial data analysis was conducted in September 2018; further analysis was conducted from February 2019 to August 2019. Interventions: Clinician and algorithmic assessment of melanoma. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of the algorithmic and specialist assessment, determined using histopathology diagnosis as the criterion standard. Results: The study population of 514 patients included 279 women (55.7%) and 484 white patients (96.8%), with a mean (SD) age of 52.1 (18.6) years. A total of 1550 images of skin lesions were included in the analysis (551 [35.6%] biopsied lesions; 999 [64.4%] control lesions); 286 images (18.6%) were used to train the algorithm, and a further 849 (54.8%) images were missing or unsuitable for analysis. Of the biopsied lesions that were assessed by the algorithm and specialists, 125 (22.7%) were diagnosed as melanoma. Of these, 77 (16.7%) were used for the primary analysis. The algorithm achieved an AUROC of 90.1% (95% CI, 86.3%-94.0%) for biopsied lesions and 95.8% (95% CI, 94.1%-97.6%) for all lesions using iPhone 6s images; an AUROC of 85.8% (95% CI, 81.0%-90.7%) for biopsied lesions and 93.8% (95% CI, 91.4%-96.2%) for all lesions using Galaxy S6 images; and an AUROC of 86.9% (95% CI, 80.8%-93.0%) for biopsied lesions and 91.8% (95% CI, 87.5%-96.1%) for all lesions using DSLR camera images. At 100% sensitivity, the algorithm achieved a specificity of 64.8% with iPhone 6s images. Specialists achieved an AUROC of 77.8% (95% CI, 72.5%-81.9%) and a specificity of 69.9%. Conclusions and Relevance: In this study, the algorithm demonstrated an ability to identify melanoma from dermoscopic images of selected lesions with an accuracy similar to that of specialists.

Growth and longevity in giant barrel sponges: Redwoods of the reef or Pines in the Indo-Pacific?

Describing life history dynamics of functionally important species is critical for successful management. Barrel sponges (Xestospongia spp.) fill ecologically important roles on coral reefs due to their large size and water column interactions. Studies of Caribbean X. muta suggest they may be up to 1000 s of years old. However, nothing is known of barrel sponge growth rates outside the Caribbean. We assessed Indo-Pacific barrel sponge demography with a focus on specific growth rate (SGR), density, and mean volume across four sites of varying habitat quality. Four growth models were compared using Akaike's Information Criterion using a multi-model inference approach. Age was extrapolated and validated based on sponge size on a shipwreck of known age. Sponges from different sites showed differences in density, volume gained, and mean volume, but not growth rates. Interestingly, SGRs were slightly slower than that of X. muta, yet growth models supported rapid growth; Indo-Pacific sponges were over twice as old as published estimates of comparably sized X. muta (53-55 as compared to 23 years of age, respectively), although extrapolation errors are likely to increase with sponge size. This suggests that barrel sponge growth rates in the Indo-Pacific might be more comparable to Pines rather than Redwoods.

Newborn screening for congenital adrenal hyperplasia in New York State.

From 2007 to 2014 the New York State (NYS) Newborn Screening (NBS) program screened 2 million newborns for congenital adrenal hyperplasia (CAH). The data was analyzed to determine factors that affect 17α-hydroxyprogesterone levels and assist in developing algorithm changes that would improve the positive predictive value of the methodology being used. The concentration of 17-OHP in dried blood spots was measured using the AutoDELFIA Neonatal 17-OHP kit (Perkin Elmer, Turku, Finland). During the 8 year period of this study 2476 babies were referred, 105 babies were diagnosed with CAH (90 with the salt-wasting (SW), 8 with simple virilizing (SV), 5 with non-classical CAH, and 2 with another enzyme deficiency) and, 14 with possible CAH. Three false negative cases with SV-CAH were reported to the program. Of the total 108 known cases, 74 (69%) infants were detected by newborn screening in the absence of clinical information, or, known family history. The incidence of CAH in NYS is 1 in 18,170 with a ratio of SW to SV of 8.2:1. The incidence of CAH is lower in Black infants than in White, Hispanic and Asian infants. Despite a lower mean birth weight, female infants have a lower mean 17-OHP value than male infants and are under-represented in the referred category. As per other NBS programs the false positive rate is exacerbated by prematurity/low birth weight and by over-early specimen collection.

Sediment impacts on marine sponges.

Changes in sediment input to marine systems can influence benthic environments in many ways. Sponges are important components of benthic ecosystems world-wide and as sessile suspension feeders are likely to be impacted by changes in sediment levels. Despite this, little is known about how sponges respond to changes in settled and suspended sediment. Here we review the known impacts of sedimentation on sponges and their adaptive capabilities, whilst highlighting gaps in our understanding of sediment impacts on sponges. Although the literature clearly shows that sponges are influenced by sediment in a variety of ways, most studies confer that sponges are able to tolerate, and in some cases thrive, in sedimented environments. Critical gaps exist in our understanding of the physiological responses of sponges to sediment, adaptive mechanisms, tolerance limits, and the particularly the effect of sediment on early life history stages.

A longitudinal study of children's depressive symptoms, self-perceptions, and cognitive distortions about the self.

This longitudinal study examined how depressive symptoms relate to children's self-perceptions and to estimates of children's cognitive distortions about the self in a nonclinical sample of children who were followed from 4th grade (n = 248) through 6th grade (n = 227). Report card grades measured children's academic competence, and teachers' ratings of children's level of peer acceptance at school indicated social acceptance. Self-reported depressive symptoms predicted a change in children's negative views of the self. Moreover, the self-perceptions of children who exhibited more symptoms of depression appeared to reflect an underestimation of their actual competence. Children's negative self-perceptions and underestimations about the self were not associated with a subsequent change in depressive symptoms. The implications of the findings for cognitive theories of depression and future research with this population are discussed.

Annotation: childhood-onset schizophrenia: clinical and treatment issues.

BACKGROUND: In the past 10 years, there has been increased research on childhood-onset schizophrenia and clear advances have been achieved. METHOD: This annotation reviews the recent clinical and treatment literature on childhood-onset schizophrenia. RESULTS: There is now strong evidence that the syndrome of childhood-onset schizophrenia exists and there are several similarities between childhood- and later-onset schizophrenia. Schizophrenia in youth can be reliably diagnosed using the same criteria employed with adults, and childhood-onset schizophrenia is predictive of schizophrenia or schizophrenia spectrum disorders in adulthood. Data is accumulating to guide pharmacological treatment strategies, and practice parameters have been developed to guide clinical care. CONCLUSIONS: Despite significant advances, there remains an urgent need for additional research on treatment and service delivery strategies. Promising work with adults highlights the importance of attending to psychosocial as well as pharmacologic treatment strategies, and the potential value of preventive interventions.