Childcare, choice and social class: Caring for young children in the UK

This paper draws on the results of two qualitative research projects examining parental engagements with the childcare market in the UK. Both projects are located in the same two London localities. One project focuses on professional middle class parents, and the other on working class families, and we discuss the key importance of social class in shaping parents' differential engagement with the childcare market, and their understandings of the role childcare plays in their children's lives. We identify and discuss the different "circuits" of care (Ball et al 1995) available to and used by families living physically close to each other, but in social class terms living in different worlds. We also consider parents' relationships with carers, and their social networks. We conclude that in order to fully understand childcare policies and practices and families' experiences of care, an analysis which encompasses social class and the workings of the childcare market is needed

Summary: Working Group on QCD and Strong Interactions

In this summary of the considerations of the QCD working group at Snowmass 2001, the roles of quantum chromodynamics in the Standard Model and in the search for new physics are reviewed, with empahsis on frontier areas in the field. We discuss the importance of, and prospects for, precision QCD in perturbative and lattice calculations. We describe new ideas in the analysis of parton distribution functions and jet structure, and review progress in small-$x$ and in polarization.Comment: Snowmass 2001. Revtex4, 34 pages, 4 figures, revised to include additional references on jets and lattice QC

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

INTRODUCTION: Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP

Selective Cholesterol Dynamics between Lipoproteins and Caveolae/Lipid Rafts

Although low-density lipoprotein (LDL) receptor-mediated cholesterol uptake through clathrin-coated pits is now well understood, the molecular details and organizing principles for selective cholesterol uptake/efflux (reverse cholesterol transport, RCT) from peripheral cells remain to be resolved. It is not yet completely clear whether RCT between serum lipoproteins and the plasma membrane occurs primarily through lipid rafts/caveolae or from non-raft domains. To begin to address these issues, lipid raft/caveolae-, caveolae-, and non-raft-enriched fractions were resolved from purified plasma membranes isolated from L-cell fibroblasts and MDCK cells by detergent-free affinity chromatography and compared with detergent-resistant membranes isolated from the same cells. Fluorescent sterol exchange assays between lipoproteins (VLDL, LDL, HDL, apoA1) and these enriched domains provided new insights into supporting the role of lipid rafts/caveolae and caveolae in plasma membrane/lipoprotein cholesterol dynamics:  (i) lipids known to be translocated through caveolae were detected (cholesteryl ester, triacylglycerol) and/or enriched (cholesterol, phospholipid) in lipid raft/caveolae fractions; (ii) lipoprotein-mediated sterol uptake/efflux from lipid rafts/caveolae and caveolae was rapid and lipoprotein specific, whereas that from non-rafts was very slow and independent of lipoprotein class; and (iii) the rate and lipoprotein specificity of sterol efflux from lipid rafts/caveolae or caveolae to lipoprotein acceptors in vitro was slower and differed in specificity from that in intact cellsconsistent with intracellular factors contributing significantly to cholesterol dynamics between the plasma membrane and lipoproteins

Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by isolated glucocorticoid deficiency with preserved mineralocorticoid secretion. Mutations in the ACTH receptor (MC2R) account for approximately 25% of all FGD cases, but since these are usually missense mutations, a degree of receptor function is frequently retained. A recent report, however, suggested that disturbances in the renin-aldosterone axis were seen in some patients with potentially more severe MC2R mutations. Furthermore, MC2R knock out mice have overt aldosterone deficiency and hyperkalaemia despite preservation of a normal zona glomerulosa. We wished to determine whether a group of patients with severe nonsense mutations of the MC2R exhibited evidence of mineralocorticoid deficiency, thereby challenging the conventional diagnostic feature of FGD which might result in diagnostic misclassification

The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests

The Implementation and Sustainment Facilitation Strategy Improved Implementation Effectiveness and Intervention Effectiveness: Results from a Cluster-Randomized, Type 2 Hybrid Trial

Background: Substance use disorders (SUDs) among people with HIV are both prevalent and problematic. The Substance Abuse Treatment to HIV care project was funded to test the Implementation and Sustainment Facilitation (ISF) strategy as an adjunct to the Addiction Technology Transfer Center (ATTC) strategy for integrating a motivational interviewing-based brief intervention (MIBI) for SUDs within HIV community-based organizations. Methods: Using a cluster-randomized, type 2 hybrid trial design, 39 HIV organizations were randomized to either (1) ATTC (n = 19) or (2) ATTC + ISF (n = 20). Each HIV organization identified two staff members to be prepared to implement the MIBI (N = 78). Subsequently, during the implementation phase, HIV organizations in each condition randomized client participants (N = 824) to one of the two intervention conditions: usual care (UC; n = 415) or UC + MIBI (n = 409). Both staff-level outcomes and client-level outcomes were examined. Results: The ISF strategy had a significant impact on the implementation effectiveness (i.e., the consistency and the quality of implementation; β = .65, p = .01) but not on time-to-proficiency (β = −.02) or level-of-sustainment (β = .09). In addition, the ISF strategy was found to have a significant impact on the intervention effectiveness (the effectiveness of the MIBI), at least in terms of significantly decreasing the odds (odds ratio = 0.11, p = .02) of clients using their primary substance daily during follow-up. Conclusion: The ISF strategy was found to be an effective adjunct to the ATTC strategy in terms of implementation effectiveness and intervention effectiveness. It is recommended that future efforts to integrate the project’s MIBI for SUD within HIV organizations use the ATTC + ISF strategy. However, given the ISF strategy did not have a significant impact on level-of-sustainment, implementation research testing the extent to which the ATTC + ISF strategy can be significantly enhanced through effective sustainment strategies is warranted. Substance use among people living with HIV is associated with increased mental health problems, worse medication adherence, and worse HIV viral suppression. Increasing substance use-related services in HIV community-based organizations is an important public health need. The Substance Abuse Treatment to HIV care project tested two strategies for helping HIV organizations implement a brief intervention (BI) designed to motivate clients to decrease their substance use. The project also tested if receiving a BI improved clients’ outcome. Two staff from each of the 39 participating organizations were taught how to deliver the BI using the Addiction Technology Transfer Center (ATTC) training strategy (online and in-person training, monthly feedback, and coaching). Half of the organizations also received the Implementation and Sustainment Facilitation (ISF) strategy, which included monthly meetings with an ISF coach for the two BI staff and one or more leadership staff from the organization. Organizations that received both the ATTC and ISF strategies delivered more BIs and higher quality BIs than organizations that only received the ATTC strategy. In addition, clients receiving BIs at organizations that received both strategies were more likely to decrease their substance use. However, receiving both strategies did not improve how quickly staff learned to deliver the BI or improve the number of BIs delivered during the project’s 6-month sustainment phase. Future research focused on implementing BIs within HIV organizations should consider using the ATTC and ISF strategies while also seeking to enhance the strategies to improve sustainment

Altering Dynamics of Autonomic Processing Therapy (ADAPT) trial: a novel, targeted treatment for reducing anxiety in joint hypermobility

Background Hypermobility is a poorly recognised and understood musculoskeletal disorder thought to affect around 20% of the population. Hypermobility is associated with reduced physiological and psychological functioning and quality of life and is a known risk factor for the development of an anxiety disorder. To date, no evidence-based, targeted treatment for anxiety in the context of hypermobility exists. The present intervention (ADAPT—Altering Dynamics of Autonomic Processing Therapy) is a novel therapy combining bio-behavioural training with cognitive approaches from clinical health psychology targeting the catastrophisation of internal sensations, with aim to improve autonomic trait prediction error. Method Eighty individuals with diagnosed hypermobility will be recruited and the efficacy of ADAPT to treat anxiety will be compared to an Emotion-Focused Supportive Therapy (EFST) comparator therapy in a randomised controlled trial. The primary treatment target will be post therapy score on the Beck Anxiety Inventory, and secondary outcomes will also be considered in relation to interoception, depression, alexithymia, social and work adjustment, panic symptoms and dissociation. Due to COVID restrictions, the intervention will be moved to online delivery and qualitative assessment of treatment tolerance to online therapy will also be assessed. Discussion Online delivery of an intervention targeting anxiety would improve the quality of life for those experiencing anxiety disorder and help to reduce the £11.7 billion that anxiety disorders cost the UK economy annually. Trial registration World Health Organization ISRCTN17018615. Registered on 20th February 2019; trial protocol version

RECQL4 helicase has oncogenic potential in sporadic breast cancers

RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund–Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer predisposition. RECQL4 is widely considered to be a tumour suppressor, although its role in human breast cancer is largely unknown. As the RECQL4 gene is localized to chromosome 8q24, a site frequently amplified in sporadic breast cancers, we hypothesized that it may play an oncogenic role in breast tumourigenesis. To address this, we analysed large cohorts for gene copy number changes (n = 1977), mRNA expression (n = 1977) and protein level (n = 1902). Breast cancer incidence was also explored in 58 patients with type II RTS. DNA replication dynamics and chemosensitivity was evaluated in RECQL4-depleted breast cancer cells in vitro. Amplification or gain in gene copy number (30.6%), high-level mRNA expression (51%) and high levels of protein (23%) significantly associated with aggressive tumour behaviour, including lymph node positivity, larger tumour size, HER2 overexpression, ER-negativity, triple-negative phenotypes and poor survival. RECQL4 depletion impaired the DNA replication rate and increased chemosensitivity in cultured breast cancer cells. Thus, although recognized as a ’safe guardian of the genome’, our data provide compelling evidence that RECQL4 is tumour promoting in established breast cancers

Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer

FEN1 has key roles in Okazaki fragment maturation during replication, long patch base excision repair, rescue of stalled replication forks, maintenance of telomere stability and apoptosis. FEN1 may be dysregulated in breast and ovarian cancers and have clinicopathological significance in patients. We comprehensively investigated FEN1 mRNA expression in multiple cohorts of breast cancer [training set (128), test set (249), external validation (1952)]. FEN1 protein expression was evaluated in 568 oestrogen receptor (ER) negative breast cancers, 894 ER positive breast cancers and 156 ovarian epithelial cancers. FEN1 mRNA overexpression was highly significantly associated with high grade (p= 4.89 x 10 - 57) , high mitotic index (p= 5.25 x 10 - 28), pleomorphism (p= 6.31 x 10-19), ER negative (p= 9.02 x 10-35 ), PR negative (p= 9.24 x 10-24 ), triple negative phenotype (p= 6.67 x 10-21) , PAM50.Her2 (p=5.19 x 10-13 ), PAM50.Basal (p=2.7 x 10-41), PAM50.LumB (p=1.56 x 10-26), integrative molecular cluster 1 (intClust.1) ( p=7.47 x 10-12), intClust.5 (p=4.05 x 10-12) and intClust. 10 (p=7.59 x 10-38 ) breast cancers. FEN1 mRNA overexpression is associated with poor breast cancer specific survival in univariate (p=4.4 x 10-16) and multivariate analysis (p=9.19 x 10-7). At the protein level, in ER positive tumours , FEN1 overexpression remains significantly linked to high grade, high mitotic index and pleomorphism (ps< 0.01). In ER negative tumours, high FEN1 is significantly associated with pleomorphism, tumour type, lymphovascular invasion, triple negative phenotype, EGFR and HER2 expression (ps<0.05). In ER positive as well as in ER negative tumours, FEN1 protein over expression is associated with poor survival in univariate and multivariate analysis (ps<0.01). In ovarian epithelial cancers , similarly, FEN1 overexpression is associated with high grade, high stage and poor survival (ps<0.05). We conclude that FEN1 is a promising biomarker in breast and ovarian epithelial cancer