From Matterhorn to Mt Everest: empowering rescuers and improving medical care in Nepal.

This article describes a private initiative in which professional Swiss rescuers, based at the foot of the Matterhorn, trained Nepalese colleagues in advanced high altitude helicopter rescue and medical care techniques. What started as a limited program focused on mountain safety has rapidly developed into a comprehensive project to improve rescue and medical care in the Mt Everest area for both foreign travelers and the local Nepalese people.

Gender inequalities in the response to combination antiretroviral therapy over time: the Swiss HIV Cohort Study

OBJECTIVES Gender-specific data on the outcome of combination antiretroviral therapy (cART) are a subject of controversy. We aimed to compare treatment responses between genders in a setting of equal access to cART over a 14-year period. METHODS Analyses included treatment-naïve participants in the Swiss HIV Cohort Study starting cART between 1998 and 2011 and were restricted to patients infected by heterosexual contacts or injecting drug use, excluding men who have sex with men. RESULTS A total of 3925 patients (1984 men and 1941 women) were included in the analysis. Women were younger and had higher CD4 cell counts and lower HIV RNA at baseline than men. Women were less likely to achieve virological suppression < 50 HIV-1 RNA copies/mL at 1 year (75.2% versus 78.1% of men; P = 0.029) and at 2 years (77.5% versus 81.1%, respectively; P = 0.008), whereas no difference between sexes was observed at 5 years (81.3% versus 80.5%, respectively; P = 0.635). The probability of virological suppression increased in both genders over time (test for trend, P < 0.001). The median increase in CD4 cell count at 1, 2 and 5 years was generally higher in women during the whole study period, but it gradually improved over time in both sexes (P < 0.001). Women also were more likely to switch or stop treatment during the first year of cART, and stops were only partly driven by pregnancy. In multivariate analysis, after adjustment for sociodemographic factors, HIV-related factors, cART and calendar period, female gender was no longer associated with lower odds of virological suppression. CONCLUSIONS Gender inequalities in the response to cART are mainly explained by the different prevalence of socioeconomic characteristics in women compared with men.

Lithium isotope constraints on crust–mantle interactions and surface processes on Mars

Lithium abundances and isotope compositions are reported for a suite of martian meteorites that span the range of petrological and geochemical types recognized to date for Mars. Samples include twenty-one bulk-rock enriched, intermediate and depleted shergottites, six nakhlites, two chassignites, the orthopyroxenite Allan Hills (ALH) 84001 and the polymict breccia Northwest Africa (NWA) 7034. Shergottites unaffected by terrestrial weathering exhibit a range in δ7Li from 2.1 to 6.2‰, similar to that reported for pristine terrestrial peridotites and unaltered mid-ocean ridge and ocean island basalts. Two chassignites have δ7Li values (4.0‰) intermediate to the shergottite range, and combined, these meteorites provide the most robust current constraints on δ7Li of the martian mantle. The polymict breccia NWA 7034 has the lowest δ7Li (−0.2‰) of all terrestrially unaltered martian meteorites measured to date and may represent an isotopically light surface end-member. The new data for NWA 7034 imply that martian crustal surface materials had both a lighter Li isotope composition and elevated Li abundance compared with their associated mantle. These findings are supported by Li data for olivine-phyric shergotitte NWA 1068, a black glass phase isolated from the Tissint meteorite fall, and some nakhlites, which all show evidence for assimilation of a low-δ7Li crustal component. The range in δ7Li for nakhlites (1.8 to 5.2‰), and co-variations with chlorine abundance, suggests crustal contamination by Cl-rich brines. The differences in Li isotope composition and abundance between the martian mantle and estimated crust are not as large as the fractionations observed for terrestrial continental crust and mantle, suggesting a difference in the styles of alteration and weathering between water-dominated processes on Earth versus possibly Cl–S-rich brines on Mars. Using high-MgO shergottites (>15 wt.% MgO) it is possible to estimate the δ7Li of Bulk Silicate Mars (BSM) to be 4.2 ± 0.9‰ (2σ). This value is at the higher end of estimates for the Bulk Silicate Earth (BSE; 3.5 ± 1.0‰, 2σ), but overlaps within uncertainty.

Ms. hebr. fol. 10 - Hilkhot Alfasi

Vorbesitzer: Abraham Merzbacher

Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children

AIM To identify novel variants associated with anthracycline-induced cardiotoxicity and to assess these in a genotype-guided risk prediction model. PATIENTS & METHODS Two cohorts treated for childhood cancer (n = 344 and 218, respectively) were genotyped for 4578 SNPs in drug ADME and toxicity genes. RESULTS Significant associations were identified in SLC22A17 (rs4982753; p = 0.0078) and SLC22A7 (rs4149178; p = 0.0034), with replication in the second cohort (p = 0.0071 and 0.047, respectively). Additional evidence was found for SULT2B1 and several genes related to oxidative stress. Adding the SLC22 variants to the prediction model improved its discriminative ability (AUC 0.78 vs 0.75 [p = 0.029]). CONCLUSION Two novel variants in SLC22A17 and SLC22A7 were significantly associated with anthracycline-induced cardiotoxicity and improved a genotype-guided risk prediction model, which could improve patient risk stratification.

Effects of ground semen collection on weight bearing on hindquarters, libido, and semen parameters in stallions

Collection of semen on the ground from the standing stallion represents an alternative method to dummy mount semen collection and is of increasing popularity for sport stallions, males suffering from health problems, or in studs without a dummy or suitable mare at disposal. Our aim was to collect and compare spermatological and physiological data associated with traditional and ground semen collection. Twelve of 23 Franches-Montagnes stallions were selected to carry out semen collection on a dummy and while standing in a crossed experimental protocol. Semen quantity and quality parameters, weight bearing on hindquarters, and behavioral and libido data were recorded. Ground versus dummy mount semen collection was accompanied by lower seminal volume (15.9 ± 14.6 vs. 22.0 ± 13.3 mL; P < 0.01) and lower total sperm count (4.913 ± 2.721 × 10(9) vs. 6.544 ± 2.856 × 10(9) sperm; P < 0.001). No significant differences were found concerning sperm motility and viability. Time to ejaculation was longer, and the number of attempts to ejaculation was higher (P = 0.053) in the standing position compared with the mount on the dummy. A higher (P < 0.01) amount of tail flagging was manifested by the stallions during ejaculation on the dummy compared to when standing. There was no difference in weight bearing on hindquarters when comparing dummy collection (51.2 ± 2.5%) and standing collection (48.9 ± 5.5%). Ground semen collection can be considered as a viable option for stallions that cannot mount a dummy or a mare. However, it requires training and may be not easily accepted by all stallions. Owners should be advised that ground semen collection is associated with significantly lower sperm numbers than with dummy mount semen collection.

The Dark Side of the Moon: Meta-analytical Impact of Recruitment Strategies on Risk Enrichment in the Clinical High Risk State for Psychosis

Background: The individual risk of developing psychosis after being tested for clinical high-risk (CHR) criteria (posttest risk of psychosis) depends on the underlying risk of the disease of the population from which the person is selected (pretest risk of psychosis), and thus on recruitment strategies. Yet, the impact of recruitment strategies on pretest risk of psychosis is unknown. Methods: Meta-analysis of the pretest risk of psychosis in help-seeking patients selected to undergo CHR assessment: total transitions to psychosis over the pool of patients assessed for potential risk and deemed at risk (CHR+) or not at risk (CHR−). Recruitment strategies (number of outreach activities per study, main target of outreach campaign, and proportion of self-referrals) were the moderators examined in meta-regressions. Results: 11 independent studies met the inclusion criteria, for a total of 2519 (CHR+: n = 1359; CHR−: n = 1160) help-seeking patients undergoing CHR assessment (mean follow-up: 38 months). The overall meta-analytical pretest risk for psychosis in help-seeking patients was 15%, with high heterogeneity (95% CI: 9%–24%, I 2 = 96, P < .001). Recruitment strategies were heterogeneous and opportunistic. Heterogeneity was largely explained by intensive (n = 11, β = −.166, Q = 9.441, P = .002) outreach campaigns primarily targeting the general public (n = 11, β = −1.15, Q = 21.35, P < .001) along with higher proportions of self-referrals (n = 10, β = −.029, Q = 4.262, P = .039), which diluted pretest risk for psychosis in patients undergoing CHR assessment. Conclusions: There is meta-analytical evidence for overall risk enrichment (pretest risk for psychosis at 38monhts = 15%) in help-seeking samples selected for CHR assessment as compared to the general population (pretest risk of psychosis at 38monhts=0.1%). Intensive outreach campaigns predominantly targeting the general population and a higher proportion of self-referrals diluted the pretest risk for psychosis.

Central European vegetation response to abrupt climate change at 8.2 ka

Oxygen isotope records show a major climatic reversal at 8.2 ka in Greenland and Europe. Annually laminated sediments from two lakes in Switzerland and Germany were sampled contiguously to assess the response of European vegetation to climate change ca. 8.2 ka with time resolution and precision comparable to those of the Greenland ice cores. The pollen assemblages show pronounced and immediate responses (0–20 yr) of terrestrial vegetation to the climatic change at 8.2 ka. A sudden collapse of Corylus avellana (hazel) was accompanied by the rapid expansion of Pinus (pine), Betula (birch), and Tilia (linden), and by the invasion of Fagus silvatica (beech) and Abies alba (fir). Vegetational changes suggest that climatic cooling reduced drought stress, allowing more drought-sensitive and taller growing species to out-compete Corylus avellana by forming denser forest canopies. Climate cooling at 8.2 ka and the immediate reorganization of terrestrial ecosystems has gone unrecognized by previous pollen studies. On the basis of our data we conclude that the early Holocene high abundance of C. avellana in Europe was climatically caused, and we question the conventional opinion that postglacial expansions of F. silvatica and A. alba were controlled by low migration rates rather than by climate. The close connection between climatic change and vegetational response at a subcontinental scale implies that forecasted global warming may trigger rapid collapses, expansions, and invasions of tree species.

Effects of Antiseptic Solutions Commonly Used in Dentistry on Bone Viability, Bone Morphology, and Release of Growth Factors

PURPOSE Antiseptic solutions are commonly used in dentistry for a number of sterilization procedures, including harvesting of bone chips, irrigation of extraction sockets, and sterilization of osteonecrotic bone. Despite its widespread use, little information is available regarding the effects of various antiseptic solutions on bone cell viability, morphology, and the release of growth factors. MATERIALS AND METHODS The antiseptic solutions included 1) 0.5% povidone iodine (PI), 2) 0.2% chlorhexidine diguluconate (CHX), 3) 1% hydrogen peroxide (H2O2), and 4) 0.25% sodium hypochlorite (HYP). Bone samples collected from porcine mandibular cortical bone were rinsed in the antiseptic solutions for 10 minutes and assessed for cell viability using an MTS assay and protein release of transforming growth factor (TGF-β1), bone morphogenetic protein 2 (BMP2), vascular endothelial growth factor (VEGF), interleukin (IL)-1β, and receptor activator of nuclear factor κB ligand (RANKL) using an enzyme-linked immunosorbent assay at 15 minutes and 4 hours after rinsing. RESULTS After antiseptic rinsing, changes to the surface protein content showed marked alterations, with an abundant protein layer remaining on CHX-rinsed bone samples. The amount of surface protein content gradually decreased in the following order: CHX, H2O2, PI, and HYP. A similar trend was also observed for the relative cell viability from within bone samples after rinsing, with up to 6 times more viable cells found in the CHX-rinsed bone samples than in the HYP- and PI-rinsed samples. An analysis of the growth factors found that both HYP and PI had significantly lower VEGF and TGF-β1 protein release from bone samples at 15 minutes and 4 hours after rinsing compared with CHX and H2O2. A similar trend was observed for RANKL and IL-1β protein release, although no change was observed for BMP2. CONCLUSIONS The results from the present study have demonstrated that antiseptic solutions present with very different effects on bone samples after 10 minutes of rinsing. Rinsing with CHX maintained significantly higher cell viability and protein release of growth factors potent to the bone remodeling cycle.

Short- and long-term efficacy and mechanism of action of tumescent suction curettage for axillary hyperhidrosis

BACKGROUND Axillary hyperhidrosis is a common and distressing problem interfering with the life of affected individuals. Currently, local surgery is the treatment of choice once conservative treatment has failed. OBJECTIVES To evaluate the clinical efficacy and safety of tumescent suction curettage (TSC) in treating axillary hyperhidrosis and to correlate it with histological markers. METHODS Thirty patients (17 females and 13 males, average age 29.9 years) underwent TSC. After tumescent anaesthesia, a suction cannula was inserted in the axilla on each side through two tiny incisions and subcutaneous tissue was removed by suction. We evaluated the clinical efficacy and complications, and in a subset of patients performed biopsies before surgery, as well as 1 month and 1 year after the operation. RESULTS In comparison with preoperative values, the sweat rate was diminished by 85% after 1 month, 71% after 6 months, 77% after 12 months and 61% after 24 months. The reduced efficacy with time was histologically correlated with an increase in the innervation, whereas the number of sweat glands continued to diminish. The majority of patients were satisfied with the operation but the satisfaction diminished with time. Patients with the highest preoperative sweat rates were the most satisfied after the intervention. CONCLUSION TSC is an effective and safe treatment for axillary hyperhidrosis. The long-term recurrence may be due to reinnervation.

A retrospective study of 1- versus 2-cm excision margins for cutaneous malignant melanomas thicker than 2 mm.

BACKGROUND Most guidelines recommend at least 2-cm excision margin for melanomas thicker than 2 mm. OBJECTIVE We evaluated whether 1- or 2-cm excision margins for melanoma (>2 mm) result in different outcomes. METHODS This is a retrospective cohort study on patients with melanomas (>2 mm) who underwent tumor excision with 1-cm (228 patients) or 2-cm (97 patients) margins to investigate presence of local recurrences, locoregional and distant metastases, and disease-free and overall survival. RESULTS In all, 325 patients with mean age of 61.84 years and Breslow thickness of 4.36 mm were considered for the study with a median follow-up of 1852 days (1995-2012). There was no significant difference in the frequency of locoregional and distant metastasis between the 2 groups (P = .311 and .571). The survival analysis showed no differences for disease-free (P = .800; hazard ratio 0.948; 95% confidence interval 0.627-1.433) and overall (P = .951; hazard ratio 1.018; 95% confidence interval 0.575-1.803) survival. LIMITATIONS The study was not prospectively randomized. CONCLUSIONS Our study did not show any significant differences in important outcome parameters such as local or distant metastases and overall survival. A prospective study testing 1- versus 2-cm excision margin is warranted.

Towards tailored radiopeptide therapy.

PURPOSE Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor. METHODS Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving (90)Y-DOTATOC, (177)Lu-DOTATOC or their combination. RESULTS (90)Y-DOTATOC plus (177)Lu-DOTATOC treatment was associated with longer survival than (90)Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or (177)Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). (177)Lu-DOTATOC was associated with longer survival than (90)Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). (90)Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5% vs. 4.0%, p = 0.005) or (177)Lu-DOTATOC (9.5 vs. 1.4%, p = 0.002). Renal toxicity was similar among the treatments. CONCLUSIONS Using (90)Y and (177)Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors.