UK National Audit of Early Syphilis Management. Case-notes audit: contact tracing, information giving, follow-up and outcomes

Contact tracing was provided for 683/781 (87%, regional range 57–97%) cases, and identified 997 traceable contacts of whom 511 (51%) were seen, short of the recommended standard of 60%. However, the performance range for this standard was 26–70%, with seven regions achieving 60% or more. Of 511, 215 (42%, range 3–73%) contacts had syphilis. Treatment completion was recorded for 691 (88%, range 71–100%) cases, and resolution of lesions for 348/469 (74%, range 40–96%) cases. Nationally, 419/764 (55%, range 37–70%) cases were recorded as having a two dilution (four-fold) or greater decrease in non-treponemal test titre within 3–6 months after treatment; not achieving this titre decrease was mainly attributable to non-attendance for follow-up and failure of titre levels to fall. Follow-up of infectious syphilis in UK genitourinary medicine clinics is poor and falls far short of that recommended by National Guidelines. Only 16 (2%) cases had follow-up at intervals approximating to 1, 2, 3, 6 and 12 months, and only 312 (40%, range 5–61%) cases attended at least two follow-up visits. Only 17 (7%) of all 236 oral treatments (including switches to oral treatment), and 33 (27%) of 123 cases with HIV infection were recorded as designated annual follow-up. Further work is needed to determine factors that account for the wide variation between regions in contact tracing and follow-up performance

Interlocking Directorates and Big Business (1816-1969): Inloc Dataset

The Inloc Dataset (Interlocking Data 1816-1969.col.xlsx), created to identify communities of interest and interlocking linkages, consists of 48,000 directors and officers of 2,600 of the largest U.S. corporations active between 1896 and 1919 and selected other years

Port-Site Hernia Following Laparoscopic Cholecystectomy

The incidence of port-site hernia is variable, but evidence suggests that awareness of risk factors and modification of technique can minimize risk

Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment

Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway, are found in 50% of patients with Noonan syndrome. These patients have an increased risk of developing leukaemia, especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity. However, the effect of these mutations in the bone marrow microenvironment remains unclear. Here we report that Ptpn11 activating mutations in the mouse bone marrow microenvironment promote the development and progression of MPN through profound detrimental effects on haematopoietic stem cells (HSCs). Ptpn11 mutations in mesenchymal stem/progenitor cells and osteoprogenitors, but not in differentiated osteoblasts or endothelial cells, cause excessive production of the CC chemokine CCL3 (also known as MIP-1α), which recruits monocytes to the area in which HSCs also reside. Consequently, HSCs are hyperactivated by interleukin-1β and possibly other proinflammatory cytokines produced by monocytes, leading to exacerbated MPN and to donor-cell-derived MPN following stem cell transplantation. Remarkably, administration of CCL3 receptor antagonists effectively reverses MPN development induced by the Ptpn11-mutated bone marrow microenvironment. This study reveals the critical contribution of Ptpn11 mutations in the bone marrow microenvironment to leukaemogenesis and identifies CCL3 as a potential therapeutic target for controlling leukaemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonan-syndrome-associated leukaemias

Current understanding in climbing psychophysiology research

The sport of rock climbing places a significant physiological and psychological load on participants. Psychophysiological analysis provides a unique insight into affective states arising from the demands of climbing, and the impact that they have on performance. This review provides an overview of climbing psychophysiology research completed to date. To summarise, an on-sight lead ascent of a route elicits the greatest psychophysiological response in climbers; whilst, a red-point top-rope ascent produces the least. The affects of climbing stimuli on an individual’s performance appear to be conditional on their experience. In general, experienced climbers show superior performance and are less anxious than their less practiced counterparts, with significantly lower cognitive and somatic anxiety, increased self-confidence and lower values of the steroid stress hormone cortisol. It is likely that the experience-stressor-performance relationship is due to advanced climbers’ greater understanding of the risks associated with the sport, their habituation to the stressors gained through practice and their ability to perform well with higher levels of anxiety. This review outlines pertinent psychological climbing stimuli, summarise current methodologies and presents a detailed review of climbing psychophysiology research. It also concludes with suggestions for improving the depth and breadth of future research, including the need for the refinement of existing measures

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference