The Paradox behind the Pattern of Rapid Adaptive Radiation: How Can the Speciation Process Sustain Itself Through an Early Burst?

Rapid adaptive radiation poses two distinct questions apart from speciation and adaptation: What happens after one speciation event and how do some lineages continue speciating through a rapid burst? We review major features of rapid radiations and their mismatch with theoretical models and speciation mechanisms. The paradox is that the hallmark rapid burst pattern of adaptive radiation is contradicted by most speciation models, which predict continuously decelerating diversification and niche subdivision. Furthermore, it is unclear if and how speciation-promoting mechanisms such as magic traits, phenotype matching, and physical linkage of coadapted alleles promote rapid bursts of speciation. We review additional mechanisms beyond ecological opportunity to explain rapid radiations: (a) ancient adaptive alleles and the transporter hypothesis, (b) sexual signal complexity, (c) fitness landscape connectivity, (d) diversity begets diversity, and (e) plasticity first. We propose new questions and predictions connecting microevolutionary processes to macroevolutionary patterns through the study of rapid radiations

Lung fibrosis in deceased HIV-infected patients with Pneumocystis pneumonia

Background. Pneumocystis pneumonia (PcP) is one of the most common opportunistic infections found in patients with HIV. The prognosis if ventilation is required is poor, with mortality of 36 - 80%. Although more recent studies have shown improved survival, our experience has been that close to 100% of such patients die, and we therefore decidedto investigate further.Methods. All patients with confirmed or suspected PcP who died owing to respiratory failure were eligible for the study. Where consent was obtained, trucut lung biopsies were performed post mortem, stored in formalin and sent for histopathological assessment.Results. Twelve adequate lung biopsies were obtained from 1 July 2008 to 28 February 2011 – 3 from men and 9 from women. The mean age was 34.7 years (range 24 - 46), and the mean admission CD4 count was 20.8(range 1 - 68) cells/ìl and median 18.5 cells/ìl. All specimens demonstrated typical PcP histopathology; in addition, 9 showed significant interstitial fibrosis. Three had co-infection with cytomegalovirus (CMV), two of which had fibrosis present. There was no evidence of TB or otherfungal infections.Conclusion. The high mortality seen in this cohort of PcP patients was due to intractable respiratory failure from interstitial lung fibrosis. Whereas the differential includes ventilator induced lung injury, drug resistanceor co-infections, we suggest that this is part of the disease progression in certain individuals. Further studies are required to identify interventions that could modify this process and improve outcomes in patients with PcP who require mechanical ventilation

Increased toxin expression in a Clostridium difficile mfd mutant

BACKGROUND: The symptoms of Clostridium difficile infection are mediated primarily by two toxins, TcdA and TcdB, the expression of which is governed by a multitude of factors including nutrient availability, growth phase and cell stress. Several global regulators have been implicated in the regulation of toxin expression, such as CcpA and CodY. RESULTS: During attempts to insertionally inactivate a putative secondary cell wall polysaccharide synthesis gene, we obtained several mutants containing off-target insertions. One mutant displayed an unusual branched colony morphology and was investigated further. Marker recovery revealed an insertion in mfd, a gene encoding a transcription-coupled repair factor. The mfd mutant exhibited pleiotropic effects, in particular increased expression of both toxin A and B (TcdA and TcdB) compared to the parental strain. Western blotting and cellular cytotoxicity assays revealed increased expression across all time points over a 24 h period, with inactivation of mfd resulting in at least a 10 fold increase in cell cytotoxicity. qRT-PCR demonstrated the upregulation of both toxins occurred on a transcriptional level. All effects of the mfd mutation were complemented by a plasmid-encoded copy of mfd, showing the effects are not due to polar effects of the intron insertion or to second site mutations. CONCLUSIONS: This study adds Mfd to the repertoire of factors involved in regulation of toxin expression in Clostridium difficile. Mfd is known to remove RNA polymerase molecules from transcriptional sites where it has stalled due to repressor action, preventing transcriptional read through. The consistently high levels of toxin in the C. difficile mfd mutant indicate this process is inefficient leading to transcriptional de-repression

Research Review: Childhood chronic physical illness and adult emotional health - a systematic review and meta-analysis

Background Childhood chronic physical illness is associated with a greater vulnerability for emotional problems (i.e. depression and anxiety) in childhood. However, little is known about life‐long effects of childhood chronic physical illness on mental health. The present study aims to systematically review evidence for associations between eight chronic physical illnesses with childhood onset (arthritis, asthma, cancer, chronic renal failure, congenital heart disease, cystic fibrosis, type 1 diabetes, and epilepsy) and adult emotional problems. Methods A database search of MEDLINE, PsycARTICLES, PsycINFO, and ScienceDirect was undertaken, and random effects meta‐analyses were used to synthesise evidence from eligible studies. Results In total, 37 studies were eligible for the systematic review (n = 45,733) and of these, 34 studies were included in the meta‐analyses (n = 45,358). There were overall associations between childhood chronic physical illness and adult depression (OR = 1.31; 95% CI [1.12, 1.54]) and anxiety (OR = 1.47; 95% CI [1.13, 1.92]). Separate meta‐analyses for childhood asthma, type 1 diabetes and cancer were also conducted, with cancer being significantly associated with adult depression (OR = 1.19; 95% CI [1.00, 1.42]). Conclusions The effects of childhood chronic physical illness on the risk of emotional problems persist beyond childhood and adolescence. Mental health prevention and intervention strategies targeting children with chronic physical illnesses can have long‐term benefits

Psychological therapies for depression and cardiovascular risk: evidence from national healthcare records in England

Aims: People with depression are up to 72% more at risk to develop cardiovascular disease (CVD) in their lifetime. Evidence-based psychotherapies are first-line interventions for the treatment of depression and are delivered nationally in England through the National Health Service via the Improving Access to Psychological Therapy (IAPT) primary care programme. It is currently unknown whether positive therapy outcomes may be associated with cardiovascular risk reduction. This study aimed to examine the association between psychotherapy outcomes for depression and incident CVD. Methods and results: A cohort of 636 955 individuals who have completed a course of psychotherapy was built from linked electronic healthcare record databases of national coverage in England: the national IAPT database, the Hospital Episode Statistics (HES) database, and the HES–ONS (Office of National Statistics) mortality database. Multivariable Cox models adjusting for clinical and demographic covariates were run to estimate the association between reliable improvement from depression and the risk of subsequent incidence of cardiovascular events. After a median follow-up of 3.1 years, reliable improvement from depression symptoms was associated with a lower risk of new onset of any CVD [hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.86, 0.89], coronary heart disease (HR: 0.89, 95% CI: 0.86, 0.92), stroke (HR: 0.88, 95% CI: 0.83, 0.94), and all-cause mortality (HR: 0.81, 95% CI: 0.78, 0.84). This association was stronger in the under 60 compared with the over 60 for all outcomes. Results were confirmed in sensitivity analyses. Conclusion: Management of depression through psychological interventions may be associated with reduced risk of CVD. More research is needed to understand the causality of these associations

Incidence of mild cognitive impairment in World Trade Center responders: Long-term consequences of re-experiencing the events on 9/11/2001

Objective: This study examined whether World Trade Center (WTC) exposures and chronic posttraumatic stress disorder (PTSD) were associated with incidence of mild cognitive impairment (MCI) in a longitudinal analysis of a prospective cohort study of WTC responders. Methods: Incidence of MCI was assessed in a clinical sample of WTC responders (N = 1800) who were cognitively intact at baseline assessment. Crude incidence rates were calculated and compared to population estimates using standardized incidence ratios. Multivariable analyses used Cox proportional-hazards regression. Results: Responders were 53.1 years old (SD = 7.9) at baseline. Among eligible cognitively intact responders, 255 (14.2%) developed MCI at follow-up. Incidence of MCI was higher than expected based on expectations from prior published research. Incidence was higher among those with increased PTSD symptom severity, and prolonged exposure was a risk factor in apolipoprotein-ε4 carriers. Conclusions: PTSD and prolonged WTC exposures were associated with increased incidence of MCI in WTC responders, results that may portend future high rates of dementia in WTC-exposed responders

Autism in England: assessing underdiagnosis in a population-based cohort study of prospectively collected primary care data

Background: Autism has long been viewed as a paediatric condition, meaning that many autistic adults missed out on a diagnosis as children when autism was little known. We estimated numbers of diagnosed and undiagnosed autistic people in England, and examined how diagnostic rates differed by socio-demographic factors. / Methods: This population-based cohort study of prospectively collected primary care data from IQVIA Medical Research Data (IMRD) compared the prevalence of diagnosed autism to community prevalence to estimate underdiagnosis. 602,433 individuals registered at an English primary care practice in 2018 and 5,586,100 individuals registered between 2000 and 2018 were included. / Findings: Rates of diagnosed autism in children/young people were much higher than in adults/older adults. As of 2018, 2.94% of 10- to 14-year-olds had a diagnosis (1 in 34), vs. 0.02% aged 70+ (1 in 6000). Exploratory projections based on these data suggest that, as of 2018, 463,500 people (0.82% of the English population) may have been diagnosed autistic, and between 435,700 and 1,197,300 may be autistic and undiagnosed (59–72% of autistic people, 0.77%–2.12% of the English population). Age-related inequalities were also evident in new diagnoses (incidence): c.1 in 250 5- to 9-year-olds had a newly-recorded autism diagnosis in 2018, vs. c.1 in 4000 20- to 49-year-olds, and c.1 in 18,000 people aged 50+. / Interpretation: Substantial age-related differences in the proportions of people diagnosed suggest an urgent need to improve access to adult autism diagnostic services

Tooth wear: the view of the anthropologist

Anthropologists have for many years considered human tooth wear a normal physiological phenomenon where teeth, although worn, remain functional throughout life. Wear was considered pathological only if pulpal exposure or premature tooth loss occurred. In addition, adaptive changes to the stomatognathic system in response to wear have been reported including continual eruption, the widening of the masticatory cycle, remodelling of the temporomandibular joint and the shortening of the dental arches from tooth migration. Comparative studies of many different species have also documented these physiological processes supporting the idea of perpetual change over time. In particular, differential wear between enamel and dentine was considered a physiological process relating to the evolution of the form and function of teeth. Although evidence of attrition and abrasion has been known to exist among hunter-gatherer populations for many thousands of years, the prevalence of erosion in such early populations seems insignificant. In particular, non-carious cervical lesions to date have not been observed within these populations and therefore should be viewed as ‘modern-day’ pathology. Extrapolating this anthropological perspective to the clinical setting has merits, particularly in the prevention of pre-mature unnecessary treatment

Salivary cortisol in longitudinal associations between affective symptoms and midlife cognitive function: A British birth cohort study

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive function; 2) Whether cortisol is associated with later depressive or anxiety symptoms, and cognitive function. Data were used from the National Child Development Study, a sample of infants born in mainland UK during one week of 1958. A measure of the accumulation of affective symptoms was derived from data collected from age 23 to 42 using the Malaise Inventory Scale. Salivary cortisol measures were available at age 44–45. Cognitive function (memory, fluency, information processing) and affective symptoms were assessed at the age of 50. Path models were run to test whether salivary cortisol explained the longitudinal association between depressive or anxiety disorder symptoms and cognitive function. Direct effects of affective symptoms are shown across early to middle adulthood on cognitive function in midlife (memory and information processing errors). However, there were no effects of affective symptoms on cognitive function through cortisol measures. Additionally, cortisol measures were not significantly associated with subsequent affective symptoms or cognitive function at the age of 50. These results do not provide clear evidence to suggest that cortisol plays a role in the association between affective symptoms and cognitive function over this period of time. These findings contribute to our understanding of how the association between affective symptoms and cognitive function operates over time