Set & Drift: Department of Defense Operations During the Cuban Crisis

A Report by Adam Yarmolinsky, Special Assistant to the Secretary of Defense, 13 February 196

Tagger's delight? Disclosure and liking in Facebook: the effects of sharing photographs amongst multiple known social circles

The present work identifies the relationship between sharing photographs with different depictions in Facebook on relationship quality, which varies depending on the type of target sharing the photographs. With over 1 billion active users, disclosure on Facebook is frequent, considered a norm of online interaction, and actively encouraged by site providers. The extant academic literature identifies Facebook as an effective tool to connect with known and unknown others, and identifies the differences in sharing behaviour when users are aware of their audience. Operating within a lowest common denominator approach to disclosure on Facebook, the present work identifies the potential consequences to personal relationships when sharing day-to-day information. Results found from a sample of 508 Facebook users suggests individuals should actively adjust their privacy settings to ensure that even amongst flattened information – i.e. that deemed appropriate for release to all target types – disclosure does not harm current and potential relationships. Implications for, users, academic theory and disclosure practice are discussed

PTEN protein phosphatase activity is not required for tumour suppression in the mouse prostate

Loss PTEN function is one of the most common events driving aggressive prostate cancers and biochemically, PTEN is a lipid phosphatase which opposes the activation of the oncogenic PI3K-AKT signalling network. However, PTEN also has additional potential mechanisms of action, including protein phosphatase activity. Using a mutant enzyme, PTEN Y138L, which selectively lacks protein phosphatase activity, we characterised genetically modified mice lacking either the full function of PTEN in the prostate gland or only lacking protein phosphatase activity. The phenotypes of mice carrying a single allele of either wild-type Pten or Pten(Y138L) in the prostate were similar, with common prostatic intraepithelial neoplasia (PIN) and similar gene expression profiles. However, the latter group, lacking PTEN protein phosphatase activity additionally showed lymphocyte infiltration around PIN and an increased immune cell gene expression signature. Prostate adenocarcinoma, elevated proliferation and AKT activation were only frequently observed when PTEN was fully deleted. We also identify a common gene expression signature of PTEN loss conserved in other studies (including Nkx3.1, Tnf and Cd44). We provide further insight into tumour development in the prostate driven by loss of PTEN function and show that PTEN protein phosphatase activity is not required for tumour suppression

The comparative effectiveness of treatments for patellofemoral pain:a living systematic review with network meta-analysis

To investigate the comparative effectiveness of all treatments for patellofemoral pain (PFP).Living systematic review with network meta-analysis (NMA).Sensitive search in seven databases, three grey literature resources and four trial registers.Randomised controlled trials evaluating any treatment for PFP with outcomes 'any improvement', and pain intensity.Two reviewers independently extracted data and assessed risk of bias with Risk of Bias Tool V.2. We used Grading of Recommendations, Assessment, Development and Evaluation to appraise the strength of the evidence.'Any improvement' measured with a Global Rating of Change Scale.Twenty-two trials (with forty-eight treatment arms) were included, of which approximately 10 (45%) were at high risk of bias for the primary outcome. Most comparisons had a low to very low strength of the evidence. All treatments were better than wait and see for any improvement at 3 months (education (OR 9.6, 95% credible interval (CrI): 2.2 to 48.8); exercise (OR 13.0, 95% CrI: 2.4 to 83.5); education+orthosis (OR 16.5, 95% CrI: 4.9 to 65.8); education+exercise+patellar taping/mobilisations (OR 25.2, 95% CrI: 5.7 to 130.3) and education+exercise+patellar taping/mobilisations+orthosis (OR 38.8, 95% CrI: 7.3 to 236.9)). Education+exercise+patellar taping/mobilisations, with (OR 4.0, 95% CrI: 1.5 to 11.8) or without orthosis (OR 2.6, 95% CrI: 1.7 to 4.2), were superior to education alone. At 12 months, education or education+any combination yielded similar improvement rates.Education combined with a physical treatment (exercise, orthoses or patellar taping/mobilisation) is most likely to be effective at 3 months. At 12 months, education appears comparable to education with a physical treatment. There was insufficient evidence to recommend a specific type of physical treatment over another. All treatments in our NMA were superior to wait and see at 3 months, and we recommend avoiding a wait-and-see approach.PROSPERO registration CRD42018079502

Gaucher Disease Glucocerebrosidase and α-Synuclein Form a Bidirectional Pathogenic Loop in Synucleinopathies

SummaryParkinson's disease (PD), an adult neurodegenerative disorder, has been clinically linked to the lysosomal storage disorder Gaucher disease (GD), but the mechanistic connection is not known. Here, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human iPS neurons compromises lysosomal protein degradation, causes accumulation of α-synuclein (α-syn), and results in neurotoxicity through aggregation-dependent mechanisms. Glucosylceramide (GlcCer), the GCase substrate, directly influenced amyloid formation of purified α-syn by stabilizing soluble oligomeric intermediates. We further demonstrate that α-syn inhibits the lysosomal activity of normal GCase in neurons and idiopathic PD brain, suggesting that GCase depletion contributes to the pathogenesis of sporadic synucleinopathies. These findings suggest that the bidirectional effect of α-syn and GCase forms a positive feedback loop that may lead to a self-propagating disease. Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies

Which treatment is most effective for patients with Achilles tendinopathy?:A living systematic review with network meta-analysis of 29 randomised controlled trials

Objective: To provide a consistently updated overview of the comparative effectiveness of treatments for Achilles tendinopathy. Design: Living systematic review and network meta-analysis. Data sources: Multiple databases including grey literature sources were searched up to February 2019. Study eligibility criteria: Randomised controlled trials examining the effectiveness of any treatment in patients wit