Functional immune characterization of HIV-associated non-small-cell lung cancer.

Dear Editor, In the combined anti-retroviral therapy (cART) era, non-small cell lung cancer (NSCLC) is a highly incident cause of morbidity and mortality in people living with HIV (PLHIV)[1]. The immune-pathogenesis of NSCLC and HIV infection both rely on programmed-death 1 (PD-1) receptor-ligand interaction as a mechanism to induce T-cell exhaustion. To date, PLHIV have been excluded from clinical trials of immune-checkpoint inhibitors (ICPI), on the presumption that anti-tumour immunity might be compromised by HIV infection. To verify this, we evaluated the clinico-pathologic significance of PD-ligands expression in a consecutive series of 221 archival NSCLC samples, 24 of which were HIV-associated (Table S1)

Pediculosis and the Pediatrician

Head lice commonly evoke feelings of disgust, revulsion, anger, and shame among parents and patients. There should, however, be no great cause for such alarm if a physician suspects pediculosis capitis. The recent introduction of several new pediculicidal drugs now allows a choice among four distinct therapeutic agents, which should substantially improve control of isolated cases and epidemics. Physicians must be aware that consumer groups are pressing public health authorities and drug manufacturers to establish proper treatment standards and safety warnings for the use of these agents. In addition, some controversy surrounds the use of lindane in children. This paper reviews the epidemiology and clinical appearance of pediculosis capitis in children, with emphasis on these recent developments. Pubic lice ( Phthirus pubis ) and body lice ( Pedicutus humanus corporis ), both of which are much less common pediatric infestations, are mentioned only briefly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72607/1/j.1525-1470.1984.tb00447.x.pd

COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study

BACKGROUND: Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK. METHODS: We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case-fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models. FINDINGS: 319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case-fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40-49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio [OR] 1·57, 95% CI 1·15-2·15; p<0·0043). Compared with the rest of the UKCCMP cohort, patients with leukaemia showed a significantly increased case-fatality rate (2·25, 1·13-4·57; p=0·023). After correction for age and sex, patients with haematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2·09, 95% CI 1·09-4·08; p=0·028). INTERPRETATION: Patients with cancer with different tumour types have differing susceptibility to SARS-CoV-2 infection and COVID-19 phenotypes. We generated individualised risk tables for patients with cancer, considering age, sex, and tumour subtype. Our results could be useful to assist physicians in informed risk-benefit discussions to explain COVID-19 risk and enable an evidenced-based approach to national social isolation policies. FUNDING: University of Birmingham and University of Oxford

First evidence for Wollemi Pine-type pollen (Dilwynites: Araucariaceae) in South America

We report the first fossil pollen from South America of the lineage that includes the recently discovered, extremely rare Australian Wollemi Pine, Wollemia nobilis (Araucariaceae). The grains are from the late Paleocene to early middle Eocene Ligorio Márquez Formation of Santa Cruz, Patagonia, Argentina, and are assigned to Dilwynites, the fossil pollen type that closely resembles the pollen of modern Wollemia and some species of its Australasian sister genus, Agathis. Dilwynites was formerly known only from Australia, New Zealand, and East Antarctica. The Patagonian Dilwynites occurs with several taxa of Podocarpaceae and a diverse range of cryptogams and angiosperms, but not Nothofagus. The fossils greatly extend the known geographic range of Dilwynites and provide important new evidence for the Antarctic region as an early Paleogene portal for biotic interchange between Australasia and South America.Mike Macphail, Raymond J. Carpenter, Ari Iglesias, Peter Wil

Alteration assemblages in Martian meteorites: implications for near-surface processes

The SNC (Shergotty-Nakhla-Chassigny) meteorites have recorded interactions between martian crustal fluids and the parent igneous rocks. The resultant secondary minerals – which comprise up to 1 vol.% of the meteorites – provide information about the timing and nature of hydrous activity and atmospheric processes on Mars. We suggest that the most plausible models for secondary mineral formation involve the evaporation of low temperature (25 – 150 °C) brines. This is consistent with the simple mineralogy of these assemblages – Fe-Mg-Ca carbonates, anhydrite, gypsum, halite, clays – and the chemical fractionation of Ca-to Mg-rich carbonate in ALH84001 "rosettes". Longer-lived, and higher temperature, hydrothermal systems would have caused more silicate alteration than is seen and probably more complex mineral assemblages. Experimental and phase equilibria data on carbonate compositions similar to those present in the SNCs imply low temperatures of formation with cooling taking place over a short period of time (e.g. days). The ALH84001 carbonate also probably shows the effects of partial vapourisation and dehydration related to an impact event post-dating the initial precipitation. This shock event may have led to the formation of sulphide and some magnetite in the Fe-rich outer parts of the rosettes. Radiometric dating (K-Ar, Rb-Sr) of the secondary mineral assemblages in one of the nakhlites (Lafayette) suggests that they formed between 0 and 670 Myr, and certainly long after the crystallisation of the host igneous rocks. Crystallisation of ALH84001 carbonate took place 0.5 Gyr after the parent rock. These age ranges and the other research on these assemblages suggest that environmental conditions conducive to near-surface liquid water have been present on Mars periodically over the last 1 Gyr. This fluid activity cannot have been continuous over geological time because in that case much more silicate alteration would have taken place in the meteorite parent rocks and the soluble salts would probably not have been preserved. The secondary minerals could have been precipitated from brines with seawater-like composition, high bicarbonate contents and a weakly acidic nature. The co-existence of siderite (Fe-carbonate) and clays in the nakhlites suggests that the pCO2 level in equilibrium with the parent brine may have been 50 mbar or more. The brines could have originated as flood waters which percolated through the top few hundred meters of the crust, releasing cations from the surrounding parent rocks. The high sulphur and chlorine concentrations of the martian soil have most likely resulted from aeolian redistribution of such aqueously-deposited salts and from reaction of the martian surface with volcanic acid volatiles. The volume of carbonates in meteorites provides a minimum crustal abundance and is equivalent to 50–250 mbar of CO2 being trapped in the uppermost 200–1000 m of the martian crust. Large fractionations in 18O between igneous silicate in the meteorites and the secondary minerals (30) require formation of the latter below temperatures at which silicate-carbonate equilibration could have taken place (400°C) and have been taken to suggest low temperatures (e.g. 150°C) of precipitation from a hydrous fluid

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Cannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues. The present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation. Maternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure. There is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans

Mindfulness-based stress reduction for people with multiple sclerosis ? a feasibility randomised controlled trial

Background: Multiple sclerosis (MS) is a stressful condition. Mental health comorbidity is common. Stress can increase the risk of depression, reduce quality of life (QOL), and possibly exacerbate disease activity in MS. Mindfulness-Based Stress Reduction (MBSR) may help, but has been little studied in MS, particularly among more disabled individuals. Methods: The objective of this study was to test the feasibility and likely effectiveness of a standard MBSR course for people with MS. Participant eligibility included: age &#62; 18, any type of MS, an Expanded Disability Status Scale (EDSS) &#60;/= 7.0. Participants received either MBSR or wait-list control. Outcome measures were collected at baseline, post-intervention, and three-months later. Primary outcomes were perceived stress and QOL. Secondary outcomes were common MS symptoms, mindfulness, and self-compassion. Results: Fifty participants were recruited and randomised (25 per group). Trial retention and outcome measure completion rates were 90% at post-intervention, and 88% at 3 months. Sixty percent of participants completed the course. Immediately post-MBSR, perceived stress improved with a large effect size (ES 0.93; p &#60; 0.01), compared to very small beneficial effects on QOL (ES 0.17; p = 0.48). Depression (ES 1.35; p &#60; 0.05), positive affect (ES 0.87; p = 0.13), anxiety (ES 0.85; p = 0.05), and self-compassion (ES 0.80; p &#60; 0.01) also improved with large effect sizes. At three-months post-MBSR (study endpoint) improvements in perceived stress were diminished to a small effect size (ES 0.26; p = 0.39), were negligible for QOL (ES 0.08; p = 0.71), but were large for mindfulness (ES 1.13; p &#60; 0.001), positive affect (ES 0.90; p = 0.54), self-compassion (ES 0.83; p &#60; 0.05), anxiety (ES 0.82; p = 0.15), and prospective memory (ES 0.81; p &#60; 0.05). Conclusions: Recruitment, retention, and data collection demonstrate that a RCT of MBSR is feasible for people with MS. Trends towards improved outcomes suggest that a larger definitive RCT may be warranted. However, optimisation changes may be required to render more stable the beneficial treatment effects on stress and depression. Trial registration: ClinicalTrials.gov Identifier NCT02136485; trial registered 1st May 2014