Adult and community education in the wear valley district of county Durham

Throughout the 1980's traditional liberal adult education * in Britain has been in crisis. Changes in the ways it is funded and organised, coupled with the breakdown of the liberal progressive ideologies which have informed its theory and practice since the turn of the century, cast doubt upon the extent to which adult education still exists as an identifiable part of the British educational system and idea. The public image of adult education is ambiguous and informed by very little public debate about the role or purpose of adult education in modern societies. its practitioner image is still, predominantly, one of public service. in this thesis i describe what happened when I set out to examine the extent to which there was still a viable adult education service (particularly for unemployed people) in a small area of the north east of England characterised by long term social and economic decline. There is very little sociology of adult education. There is no theoretical knowledge base upon which to ground this study and no methodological framework within which to situate it. The research has been, primarily, a search for methods of research which would allow that adult education is both a social construction and a cultural phenomenon. I have drawn heavily upon the methods of both cultural studies and cultural anthropology while eschewing their more descriptive moments, believing, in the end, that sociology has a definite de-mystifying purpose: that it is, or should be, 'the critic of the absurd and not its high priest'

Genome-Wide Association Study in Obsessive-Compulsive Disorder: Results from the OCGAS

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients, with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1 065 families (containing 1 406 patients with OCD), combined with population-based samples (resulting in a total sample of 5 061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at SNP- and gene-levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13×10−7). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of GWAS signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2, and PTPRD. Analyses at the gene-level revealed association of IQCK and C16orf88 (both P<1×10−6, experiment-wide significant), as well as OFCC1 (P=6.29×10−5). The suggestive findings in this study await replication in larger samples

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Cervico-Ocular and Vestibulo-Ocular Reflexes in Subclinical Neck Pain and Healthy Individuals: A Cross-Sectional Study

Alterations in neck sensory input from recurrent neck pain (known as subclinical neck pain (SCNP)) result in disordered sensorimotor integration (SMI). The cervico-ocular (COR) and vestibulo-ocular (VOR) reflexes involve various neural substrates but are coordinated by the cerebellum and reliant upon proprioceptive feedback. Given that proprioception and cerebellar processing are impaired in SCNP, we sought to determine if COR or VOR gain is also altered. COR and VOR were assessed using an eye-tracking device in 20 SCNP (9 M and 11 F; 21.8 (SD = 2.35) years) and 17 control (7 M and 10 F; 22.40 (SD = 3.66) years) participants. COR gain (10 trials): A motorized chair rotated the trunk at a frequency of 0.04 Hz and an amplitude of 5° while participants gazed at a circular target that disappeared after three seconds. VOR gain (30 trials): Rapid bilateral head movements away from a disappearing circular target while eyes fixated on the last observed target. Independent t-tests on COR and VOR gain were performed. SCNP had a significantly larger COR gain (p = 0.006) and smaller VOR gain (p = 0.487) compared to healthy controls. The COR group differences suggest an association between proprioceptive feedback and SMI, indicating COR may be a sensitive marker of altered cerebellar processing

Mean CBI₅₀ responses in each group.

<p>(A) Mean CBI₅₀ response in healthy controls before and after the combined intervention of sham control and motor sequence acquisition. (B) Mean CBI₅₀ response in neck pain control group before and after the combined intervention of sham control and motor sequence learning. (C) Mean CBI response in spinal manipulation group before and after the combined intervention of spinal manipulation and motor sequence learning. Pre motor, prior to spinal manipulation/sham control and motor sequence acquisition; Post motor, following spinal manipulation/sham control and motor sequence acquisition. Error bars depict SEM. *<i>P</i> < 0.001.</p

Mean response time and accuracy pre- and post-motor acquisition.

<p>(A) Healthy participants had marginally reduced response time and had no change to accuracy. (B) Neck pain sham control had moderate reduction to response time and dramatically improved accuracy. (C) Neck pain treatment dramatically reduced response time and had only marginal increase to accuracy. (D) All subjects demonstrated overall reduction to response time and accuracy from pre- to post-motor acquisition. Error bars depict 1 SEM. Pre, pre-motor acquisition; Post, post-acquisition. * <i>P</i> = 0.02–0.04; ** <i>P</i> = 0.005; *** <i>P</i> ≤ 0.001.</p