Trophic relationships in soil communities: how abiotic stress affects biotic interactions in the McMurdo Dry Valleys, Antarctica

2018 Summer.Includes bibliographical references.To view the abstract, please see the full text of the document

An Examination of South Carolina’s Institutions of Reform and Their Impact on the Self-Narratives of African American Men

In the State of South Carolina (SC), African American male adolescents disproportionately face disciplinary action in public schools and other institutions. In 2013, South Carolina’s Department of Juvenile Justice (SCDJJ) released data that listed Black male children comprising 57% of all juvenile referrals in the state. This disproportionate trend is also present in South Carolina’s correctional system. In 2013, South Carolina’s Department of Corrections (SCDOC) reported that out of 20,777 male prisoners, 13,631 were Black. For adolescents or young adults looking to continue their education, alternative programs are available. One program that captures educationally displaced children in South Carolina is “Construct, SC”1 (CSC). It is one of four affiliate programs of a national non-profit, “Construct, USA”2 (CUSA), that operates in the state. The research carried out considers the efficacy of one affiliate to deliver program outcomes and includes critical insights of the author working at that affiliate’s program site. The racial and correctional implications of school removal inform discussions on South Carolina’s institutional framework in the lives of Black adolescents and young adults today. A critical theoretical approach is employed in this paper to examine the state agencies most prevalent in the lives of Black men, in a bid to ascertain how the observed disproportionate trends developed. The paper incorporates five interviews conducted with men enrolled in CSC. The interviews outline their experiences in public school, the juvenile justice and state corrections systems. This paper argues that the structural inequalities that impact African Americans today correlate closely with those of South Carolina’s slave-holding past. Indeed this history is the basis for the state’s development and upkeep of its contemporary correctional culture and delinquency reform strategies against Black boys and men. Facilities that were established and in operation until the 1970s are understood to be at the epicenter of subsequent inter-generational societal and achievement deficits among Black men in the state

Long-term prognosis for individuals with hypertension undergoing coronary artery calcium scoring

To examine the performance of coronary artery calcification (CAC) for stratifying long-term risk of death in asymptomatic hypertensive patients

Predicting the future of ALS: the impact of demographic change and potential new treatments on the prevalence of ALS in the United Kingdom, 2020-2116

OBJECTIVE To model the effects of demographic change under various scenarios of possible future treatment developments in ALS. METHODS Patients diagnosed with ALS at the King's College Hospital Motor Nerve Clinic between 2004 and 2017, and living within the London boroughs of Lambeth, Southwark, and Lewisham (LSL), were included as incident cases. We also ascertained incident cases from the Canterbury region over the same period. Future incidence of ALS was estimated by applying the calculated age- and sex-specific incidence rates to the UK population projections from 2020 to 2116. The number of prevalent cases for each future year was estimated based on an established method. Assuming constant incidence, we modelled four possible future prevalence scenarios by altering the median disease duration for varying subsets of the population, to represent the impact of new treatments. RESULTS The total number of people newly diagnosed with ALS per year in the UK is projected to rise from a baseline of 1415 UK cases in 2010 to 1701 in 2020 and 2635 in 2116. Overall prevalence of ALS was predicted to increase from 8.58 per 100,000 persons in 2020 to 9.67 per 100,000 persons in 2116. Halting disease progression in patients with C9orf72 mutations would yield the greatest impact of the modelled treatment scenarios, increasing prevalence in the year 2066 from a baseline of 9.50 per 100,000 persons to 15.68 per 100,000 persons. CONCLUSIONS Future developments in treatment would combine with the effects of demographic change to result in more people living longer with ALS

Oligodendrocytes contribute to motor neuron death in ALS via SOD1 dependent mechanism

Oligodendrocytes have recently been implicated in the pathophysiology of ALS. Here we show that, in vitro, mutant SOD1 mouse oligodendrocytes induce wild-type motor neuron hyperexcitability and death. Moreover, we efficiently derived human oligodendrocytes from a large number of controls, sporadic and familial ALS patients using two different reprogramming methods. All ALS oligodendrocyte lines induced motor neuron death through conditioned medium and in co-culture. Conditioned medium-mediated motor neuron death was associated with decreased lactate production and release, while toxicity in co-culture was lactate independent, demonstrating that motor neuron survival is not only mediated by soluble factors. Remarkably, human SOD1 shRNA treatment resulted in motor neuron rescue in both mouse and human cultures when knockdown was achieved in progenitor cells, while it was ineffective in differentiated oligodendrocytes. Early SOD1 knockdown, in fact, rescued lactate impairment and cell toxicity in all lines tested with exclusion of samples carrying C9orf72 repeat expansions. These did not respond to SOD1 knockdown nor showed lactate release impairment. Our data indicate that SOD1 is directly or indirectly involved in ALS oligodendrocyte pathology and suggest that in this cell type some damage might be irreversible. In addition, we demonstrate that C9ORF72 patients represent an independent patient group that might not respond to the same treatment

Prostatic relapse of an undifferentiated teratoma 24 years after orchidectomy.

BACKGROUND: Non-seminomatous germ cell tumours make up about 40 % of all germ cell tumours, which in turn are the most common tumours in men aged 15-44 years. Low risk stage I non-seminomatous germ cell tumours, which are confined to the testes, are commonly treated by orchiectomy and surveillance. Up to 20 % of patients with this diagnosis relapse, usually within 1-2 years of follow up, but very rarely after more than 5 years. The most common sites of relapse are the retroperitoneal lymph nodes, the mediastinum, and the lungs. We describe a case of relapse in the prostate over 20 years after initial diagnosis, which has not been described in the literature so far. CASE PRESENTATION: This report presents a 49-year-old white British man with relapsed testicular non-seminomatous germ cell tumour 22 years after initial treatment with orchidectomy only. He relapsed with a prostatic mass, haematospermia and back pain. His prostate specific antigen levels were within normal range. Alpha feto-protein and lactate dehydrogenase levels were elevated, and his human chorionic gonadotrophin levels were normal. A biopsy confirmed undifferentiated malignant tumour, shown immunohistochemically to be a yolk sac tumour. The patient was initially treated with bleomycin, etoposide and cisplatin chemotherapy, but developed bleomycin-related pulmonary side effects after two cycles. His treatment was changed and he completed four cycles of chemotherapy by receiving two cycles of etoposide, ifosfamide, and cisplatin. Post treatment blood tumour markers were normal, but a follow up computed tomography showed a mass in the base of the prostate, the trigone and the left distal ureter which was surgically resected. The histology from the surgical resection was of necrotic tissue. The patient is now in follow up at 3 years after treatment with no evidence of residual disease on computed tomography. His Alpha feto-protein, beta human chorionic gonadotrophin and lactate dehydrogenase levels are normal. CONCLUSIONS: Very late relapse in stage I non-seminomatous germ cell tumours is extremely rare and the prostate is a highly unusual site of relapsed disease. For diagnosis of late relapse, this case confirms the value of serum biomarkers in germ cell tumours, in particular non-seminomatous germ cell tumours.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13104-015-1445-

C9orf72 intermediate expansions of 24–30 repeats are associated with ALS

The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~ 40% familial cases and ~ 7% sporadic cases in the European population. In most people, the repeat length is 2, but in people with ALS, hundreds to thousands of repeats may be observed. A small proportion of people have an intermediate expansion, of the order of 20 to 30 repeats in size, and it remains unknown whether intermediate expansions confer risk of ALS in the same way that massive expansions do. We investigated the association of this intermediate repeat with ALS by performing a meta-analysis of four previously published studies and a new British/Alzheimer’s Disease Neuroimaging Initiative dataset of 1295 cases and 613 controls. The final dataset comprised 5071 cases and 3747 controls. Our meta-analysis showed association between ALS and intermediate C9orf72 repeats of 24 to 30 repeats in size (random-effects model OR = 4.2, 95% CI = 1.23–14.35, p-value = 0.02). Furthermore, we showed a different frequency of the repeat between the northern and southern European populations (Fisher’s exact test p-value = 5 × 10− 3). Our findings provide evidence for the association between intermediate repeats and ALS (p-value = 2 × 10− 4) with direct relevance for research and clinical practice by showing that an expansion of 24 or more repeats should be considered pathogenic

A pragmatic randomised controlled trial assessing the non-inferiority of counselling for depression versus cognitive-behaviour therapy for patients in primary care meeting a diagnosis of moderate or severe depression (PRaCTICED): Study protocol for a randomised controlled trial.

BACKGROUND: NICE guidelines state cognitive behavioural therapy (CBT) is a front-line psychological treatment for people presenting with depression in primary care. Counselling for Depression (CfD), a form of Person-Centred Experiential therapy, is also offered within Improving Access to Psychological Therapies (IAPT) services for moderate depression but its effectiveness for severe depression has not been investigated. A full-scale randomised controlled trial to determine the efficacy and cost-effectiveness of CfD is required. METHODS: PRaCTICED is a two-arm, parallel group, non-inferiority randomised controlled trial comparing CfD against CBT. It is embedded within the local IAPT service using a stepped care service delivery model where CBT and CfD are routinely offered at step 3. Trial inclusion criteria comprise patients aged 18 years or over, wishing to work on their depression, judged to require a step 3 intervention, and meeting an ICD-10 diagnosis of moderate or severe depression. Patients are randomised using a centralised, web-based system to CfD or CBT with each treatment being delivered up to a maximum 20 sessions. Both interventions are manualised with treatment fidelity tested via supervision and random sampling of sessions using adherence/competency scales. The primary outcome measure is the Patient Health Questionnaire-9 collected at baseline, 6 and 12 months. Secondary outcome measures tap depression, generic psychological distress, anxiety, functioning and quality of life. Cost-effectiveness is determined by a patient service receipt questionnaire. Exit interviews are conducted with patients by research assessors blind to treatment allocation. The trial requires 500 patients (250 per arm) to test the non-inferiority hypothesis of -2 PHQ-9 points at the one-sided, 2.5% significance level with 90% power, assuming no underlying difference and a standard deviation of 6.9. The primary analysis will be undertaken on all patients randomised (intent to treat) alongside per-protocol and complier-average causal effect analyses as recommended by the extension to the CONSORT statement for non-inferiority trials. DISCUSSION: This large-scale trial utilises routinely collected outcome data as well as specific trial data to provide evidence of the comparative efficacy and cost-effectiveness of Counselling for Depression compared with Cognitive Behaviour Therapy as delivered within the UK government's Improving Access to Psychological Therapies initiative. TRIAL REGISTRATION: Controlled Trials ISRCTN Registry, ISRCTN06461651 . Registered on 14 September 2014

A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10% of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2. We found 11 patients (1%) carried more than one pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic lateral sclerosis. These findings show that the genetic architecture of amyotrophic lateral sclerosis is complex and that variation in the regulatory regions of associated genes may be important in disease pathogenesis

Can biodiversity of preexisting and created salt marshes match across scales? An assessment from microbes to predators

Coastal wetlands are rapidly disappearing worldwide due to a variety of processes, including climate change and flood control. The rate of loss in the Mississippi River Delta is among the highest in the world and billions of dollars have been allocated to build and restore coastal wetlands. A key question guiding assessment is whether created coastal salt marshes have similar biodiversity to preexisting, reference marshes. However, the numerous biodiversity metrics used to make these determinations are typically scale dependent and often conflicting. Here, we applied ecological theory to compare the diversity of different assemblages (surface and below-surface soil microbes, plants, macroinfauna, spiders, and on-marsh and off-marsh nekton) between two created marshes (4–6 years old) and four reference marshes. We also quantified the scale-dependent effects of species abundance distribution, aggregation, and density on richness differences and explored differences in species composition. Total, between-sample, and within-sample diversity (γ, β, and α, respectively) were not consistently lower at created marshes. Richness decomposition varied greatly among assemblages and marshes (e.g., soil microbes showed high equitability and α diversity, but plant diversity was restricted to a few dominant species with high aggregation). However, species abundance distribution, aggregation, and density patterns were not directly associated with differences between created and reference marshes. One exception was considerably lower density for macroinfauna at one of the created marshes, which was drier because of being at a higher elevation and having coarser substrate compared with the other marshes. The community compositions of created marshes were more dissimilar than reference marshes for microbe and macroinfauna assemblages. However, differences were small, particularly for microbes. Together, our results suggest generally similar taxonomic diversity and composition between created and reference marshes. This provides support for the creation of marsh habitat as tools for the maintenance and restoration of coastal biodiversity. However, caution is needed when creating marshes because specific building and restoration plans may lead to different colonization patterns