Identifying opportunities for timely diagnosis of bladder and renal cancer via abnormal blood tests: a longitudinal linked data study.

BACKGROUND: Understanding pre-diagnostic test use could reveal diagnostic windows where more timely evaluation for cancer may be indicated. AIM: To examine pre-diagnostic patterns of results of abnormal blood tests in patients with bladder and renal cancer. DESIGN AND SETTING: A retrospective cohort study using primary care and cancer registry data on patients with bladder and renal cancer who were diagnosed between April 2012 and December 2015 in England. METHOD: The rates of patients with a first abnormal result in the year before cancer diagnosis, for 'generic' (full blood count components, inflammatory markers, and calcium) and 'organ-specific' blood tests (creatinine and liver function test components) that may lead to subsequent detection of incidental cancers, were examined. Poisson regression was used to detect the month during which the cohort's rate of each abnormal test started to increase from baseline. The proportion of patients with a test found in the first half of the diagnostic window was examined, as these 'early' tests might represent opportunities where further evaluation could be initiated. RESULTS: Data from 4533 patients with bladder and renal cancer were analysed. The monthly rate of patients with a first abnormal test increased towards the time of cancer diagnosis. Abnormalities of both generic (for example, high inflammatory markers) and organ-specific tests (for example, high creatinine) started to increase from 6-8 months pre-diagnosis, with 25%-40% of these patients having an abnormal test in the 'early half' of the diagnostic window. CONCLUSION: Population-level signals of bladder and renal cancer can be observed in abnormalities in commonly performed primary care blood tests up to 8 months before diagnosis, indicating the potential for earlier diagnosis in some patients

Portfolio Vol. III N 4

Moll, Willlie. I Was in Kitchener Camp. Prose. 5-6. Barrington, John. The Pledging of Homer McGunk. Prose. 7-9. Stewart, John. In Time of Death. Prose. 10. Lindsey, Arthur Ward. Retrospect. Prose. 11-13. Phillips, Allison. Blue Moon. Poetry. 14. Yoxall, Lindsey E. Pro Patria. Prose. 15-16. Beckham, Adela. Wind--Dreams. Poetry. 18. Fields, Brooks. The Doctor Takes a Trip. Prose. 19-20. Deane, Dorothy. Review of New Books. Prose. 21. Smith, Duke. Review of New Recordings. Prose. 21. Timrud, David. Refugee. Prose. 22-23

Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies

Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding

Health service needs and perspectives of remote forest communities in Papua New Guinea: study protocol for combined clinical and rapid anthropological assessments with parallel treatment of urgent cases

Introduction Our project follows community requests for health service incorporation into conservation collaborations in the rainforests of Papua New Guinea (PNG). This protocol is for health needs assessments, our first step in coplanning medical provision in communities with no existing health data. Methods and analysis The study includes clinical assessments and rapid anthropological assessment procedures (RAP) exploring the health needs and perspectives of partner communities in two areas, conducted over 6 weeks fieldwork. First, in Wanang village (population c.200), which is set in lowland rainforest. Second, in six communities (population c.3000) along an altitudinal transect up the highest mountain in PNG, Mount Wilhelm. Individual primary care assessments incorporate physical examinations and questioning (providing qualitative and quantitative data) while RAP includes focus groups, interviews and field observations (providing qualitative data). Given absence of in-community primary care, treatments are offered alongside research activity but will not form part of the study. Data are collected by a research fellow, primary care clinician and two PNG research technicians. After quantitative and qualitative analyses, we will report: ethnoclassifications of disease, causes, symptoms and perceived appropriate treatment; community rankings of disease importance and service needs; attitudes regarding health service provision; disease burdens and associations with altitudinal-related variables and cultural practices. To aid wider use study tools are in online supplemental file, and paper and ODK versions are available free from the corresponding author. Ethics and dissemination Challenges include supporting informed consent in communities with low literacy and diverse cultures, moral duties to provide treatment alongside research in medically underserved areas while minimising risks of therapeutic misconception and inappropriate inducement, and PNG research capacity building. Brighton and Sussex Medical School (UK), PNG Institute of Medical Research and PNG Medical Research Advisory Committee have approved the study. Dissemination will be via journals, village meetings and plain language summaries

Sherman, Shakers, and Shenanigans

The first 122 pages of this book relate to Bulloch County and form Book 10: Readings in Bulloch County History. The remainder comprise the Southern Folkways Journal Review No. 3, and relate to Southeast Georgia and to the Southeastern region of the United States. The first collection begins with a poem by Dr. John Ransom Lewis, followed by three articles on Dan Bland and the biographies of prominent African American citizens. Also included are two articles on the Hardy Moore family, student papers on vanishing Bulloch County communities, information on Joseph Jackson, articles on three local churches, and the Muster Roll of Toombs Guards. The second section of this book begins with an article on Western Shakers by Dr. Dale Covington, followed by “Hostau Reminisces,” and several articles on the Cherokee and the Lumbee Indians.https://digitalcommons.georgiasouthern.edu/bchs-pubs/1033/thumbnail.jp

Spitzer Reveals Evidence of Molecular Absorption in the Atmosphere of the Hot Neptune LTT 9979b

Non-rocky sub-jovian exoplanets in high irradiation environments are rare. LTT 9979b, also known as TESS Object of Interest (TOI) 193.01, is one of the few such planets discovered to date, and the first example of an ultra-hot Neptune. The planet's bulk density indicates that it has a substantial atmosphere, so to investigate its atmospheric composition and shed further light on its origin, we obtained {\it Spitzer} IRAC secondary eclipse observations of LTT 9979b at 3.6 and 4.5 $\mu$m. We combined the {\it Spitzer} observations with a measurement of the secondary eclipse in the {\it TESS} bandpass. The resulting secondary eclipse spectrum strongly prefers a model that includes CO absorption over a blackbody spectrum, incidentally making LTT 9979b the first {\it TESS} exoplanet (and the first ultra-hot Neptune) with evidence of a spectral feature in its atmosphere. We did not find evidence of a thermal inversion, at odds with expectations based on the atmospheres of similarly-irradiated hot Jupiters. We also report a nominal dayside brightness temperature of 2305 $\pm$ 141 K (based on the 3.6 $\mu$m secondary eclipse measurement), and we constrained the planet's orbital eccentricity to $e < 0.01$ at the 99.7 \% confidence level. Together with our analysis of LTT 9979b's thermal phase curves reported in a companion paper, our results set the stage for similar investigations of a larger sample of exoplanets discovered in the hot Neptune desert, investigations which are key to uncovering the origin of this population.Comment: 12 pages, 5 figures; accepted to ApJ Letter

Predicting range shifts of African apes under global change scenarios

Aim: Modelling African great ape distribution has until now focused on current or past conditions, while future scenarios remain scarcely explored. Using an ensemble forecasting approach, we predicted changes in taxon-specific distribution under future scenarios of climate, land use and human populations for (1) areas outside protected areas (PAs) only (assuming complete management effectiveness of PAs), (2) the entire study region and (3) interspecies range overlap. Location: Tropical Africa. Methods: We compiled occurrence data (n = 5,203) on African apes from the IUCN A.P.E.S. database and extracted relevant climate-, habitat- and human-related predictors representing current and future (2050) conditions to predict taxon-specific range change under a best- and a worst-case scenario, using ensemble forecasting. Results The predictive performance of the models varied across taxa. Synergistic interactions between predictors are shaping African ape distribution, particularly human-related variables. On average across taxa, a range decline of 50% is expected outside PAs under the best scenario if no dispersal occurs (61% in worst scenario). Otherwise, an 85% range reduction is predicted to occur across study regions (94% worst). However, range gains are predicted outside PAs if dispersal occurs (52% best, 21% worst), with a slight increase in gains expected across study regions (66% best, 24% worst). Moreover, more than half of range losses and gains are predicted to occur outside PAs where interspecific ranges overlap. Main Conclusions: Massive range decline is expected by 2050, but range gain is uncertain as African apes will not be able to occupy these new areas immediately due to their limited dispersal capacity, migration lag and ecological constraints. Given that most future range changes are predicted outside PAs, Africa's current PA network is likely to be insufficient for preserving suitable habitats and maintaining connected ape populations. Thus, conservation planners urgently need to integrate land use planning and climate change mitigation measures at all decision-making levels both in range countries and abroad

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability

Chimpanzee accumulative stone throwing

The study of the archaeological remains of fossil hominins must rely on reconstructions to elucidate the behaviour that may have resulted in particular stone tools and their accumulation. Comparatively, stone tool use among living primates has illuminated behaviours that are also amenable to archaeological examination, permitting direct observations of the behaviour leading to artefacts and their assemblages to be incorporated. Here, we describe newly discovered stone tool-use behaviour and stone accumulation sites in wild chimpanzees reminiscent of human cairns. In addition to data from 17 mid- to long-term chimpanzee research sites, we sampled a further 34 Pan troglodytes communities. We found four populations in West Africa where chimpanzees habitually bang and throw rocks against trees, or toss them into tree cavities, resulting in conspicuous stone accumulations at these sites. This represents the first record of repeated observations of individual chimpanzees exhibiting stone tool use for a purpose other than extractive foraging at what appear to be targeted trees. The ritualized behavioural display and collection of artefacts at particular locations observed in chimpanzee accumulative stone throwing may have implications for the inferences that can be drawn from archaeological stone assemblages and the origins of ritual sites