Prospective surveillance of varicella-zoster virus infections in an out-patient setting in Switzerland

Limited data are available on the clinical impact of varicella in the ambulatory setting. Our goal was to determine real-life data on the clinical outcomes, medical management, and resource utilization in patients with varicella in Switzerland, a country without a universal immunization program against varicella. A total of 236 patients (222 = 94% primarily healthy individuals) with a clinical diagnosis of varicella were recruited by pediatricians and general practitioners. Age range of patients was 0-47 years with a median of 5 years. The great majority of patients (179 = 76%) were primary cases, 18 (16%) were co-primary cases, 75 (67%) were secondary cases, and 2 cases (2%) were not directly linked to the index case. A total of 29 complications were observed in 26 (11%) of 236 patients, none of them with a known underlying disease and all subsided without apparent sequelae. All complications occurred in children under 12 years of age. In conclusion, this study describes the spectrum of varicella in an out-patient setting with a sizeable rate of complications and raises the question of the value of prophylactic immunization.

Chondrosarcoma of the mobile spine and sacrum.

Chondrosarcoma is a rare malignant tumor of bone. This family of tumors can be primary malignant tumors or a secondary malignant transformation of an underlying benign cartilage tumor. Pain is often the initial presenting complaint when chondrosarcoma involves the spine. In the mobile spine, chondrosarcoma commonly presents within the vertebral body and shows a predilection for the thoracic spine. Due to the resistance of chondrosarcoma to both radiation and chemotherapy, treatment is focused on surgery. With en bloc excision of chondrosarcoma of the mobile spine and sacrum patients can have local recurrence rates as low as 20%.

Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: Multicentre, open-label, phase II safety study

PURPOSE: We assessed the safety of the multikinase inhibitor regorafenib in patients with hepatocellular carcinoma (HCC) that had progressed following first-line sorafenib. PATIENTS AND METHODS: Thirty-six patients with Barcelona Clinic Liver Cancer stage B or C HCC and preserved to mildly impaired liver function (Child-Pugh class A) received regorafenib 160 mg once daily in cycles of 3 weeks on/1 week off treatment until disease progression, unacceptable toxicity, death or patient/physician decision to discontinue. The primary end-point was safety; secondary end-points included efficacy (including time to progression and overall survival). RESULTS: The median treatment duration was 19.5 weeks (range 2-103). At data cutoff, three patients remained on treatment. Reasons for discontinuation were adverse events (n=20), disease progression (n=10), consent withdrawal (n=2) and death (n=1). Seventeen patients required dose reductions (mostly for adverse events [n=15]); 35 patients had treatment interruption (mostly for adverse events [n=32] or patient error [n=11]). The most frequent treatment-related adverse events were hand-foot skin reaction (any grade n=19; grade ≥3 n=5), diarrhoea (n=19; n=2), fatigue (n=19; n=6), hypothyroidism (n=15; n=0), anorexia (n=13; n=0), hypertension (n=13; n=1), nausea (n=12; n=0) and voice changes (n=10; n=0). Disease control was achieved in 26 patients (partial response n=1; stable disease n=25). Median time to progression was 4.3 months. Median overall survival was 13.8 months. CONCLUSION: Regorafenib had acceptable tolerability and evidence of antitumour activity in patients with intermediate or advanced HCC that progressed following first-line sorafenib.

Automated low flow pump system for the treatment of refractory ascites: A multi-center safety and efficacy study

BACKGROUND & AIMS: Refractory ascites (RA) affects 10% of patients with advanced cirrhosis and ascites. Usual therapy includes large volume paracentesis, and in selected patients, a transjugular portosystemic shunt (TIPS). These therapies may be associated with increased morbidity: paracentesis may induce circulatory dysfunction and impair quality of life and TIPS may induce encephalopathy and is associated with increased mortality in patients with severe liver dysfunction. We present the results of a multicenter, non-randomized trial to assess the safety and efficacy of a new automated pump system for treatment of RA. METHODS: Forty patients at 9 centers (February 2010-June 2011) received an implanted pump for the automated removal of ascites from the peritoneal cavity into the bladder, from where it was eliminated through normal urination. Patients were followed-up for 6months. The primary study outcome was safety. Secondary outcomes included recurrence of tense ascites and pump performance. RESULTS: Surgical complications occurred early in the study and became less frequent. The pump system removed 90% of the ascites and significantly reduced the median number of large volume paracentesis per month [3.4 (range 1-6) vs. 0.2 (range 0-4); p <0.01]. Cirrhosis-related adverse events decreased along follow-up. CONCLUSIONS: The automated pump seems an efficacious tool to move out ascites from the peritoneal cavity to the bladder. Its safety is still moderate, but a broad use in different countries will improve the surgical technique as well as the medical surveillance. A prospective randomized clinical trial vs. large volume paracentesis is underway to confirm these preliminary results.

Stabilization of subcritical bypass transition in the leading-edge boundary layer by suction

This work investigates the subcritical spatial transition in the swept Hiemenz boundary layer by means of direct numerical simulations (DNS). A pair of steady co-rotating vortices located at the attachment line is enforced as a primary disturbance leading to streaks which are stable. A small secondary, time-dependent disturbance interacts with these streaks such that instability and breakdown to turbulence may occur. The instability only occurs for a certain band of secondary disturbance frequencies. Positive secondary instability growth rates could be observed for Reynolds numbers as low as , whereas the linear critical Reynolds number is. Uniform wall suction is shown to stabilise this transition mechanism, analogously to results from linear stability theory. The effects of suction on the formation of primary streaks and on the secondary growth rate are decoupled. For streaks of different suction whose amplitude is held constant by adjusting the Reynolds number, the suction is shown to increase the growth rate of the secondary instability. The stabilising influence of wall suction consists in decreasing the streak amplitude only. Depending on the Reynolds number and the suction strength, breakdown may either occur locally and may be convected along the far-field streamlines, or occur globally and cover broad regions in the downstream direction.

Stent placement vs. balloon angioplasty for popliteal artery treatment: two-year results of a prospective, multicenter, randomized trial.

PURPOSE To investigate the 2-year technical and clinical results of primary nitinol stent placement in comparison with percutaneous transluminal angioplasty (PTA) in the treatment of de novo lesions of the popliteal artery. METHODS The ETAP study (Endovascular Treatment of Atherosclerotic Popliteal Artery Lesions: balloon angioplasty vs. primary stenting; www.ClinicalTrials.gov identifier NCT00712309) is a prospective, randomized trial that enrolled 246 patients (158 men; mean age 72 years) who were randomly assigned to receive a nitinol stent (n=119) or PTA (n=127) for lesions averaging 42.3 mm in length. The results of the primary study endpoint were published. Secondary outcome measures and endpoints included primary patency (freedom from duplex-detected target lesion restenosis), target lesion revascularization (TLR), secondary patency, changes in ankle-brachial index and Rutherford class, and event-free survival (freedom from target limb amputation, TLR, myocardial infarction, and death). RESULTS In total, 183 patients (89 stent and 94 PTA) were available for the 2-year analysis. The primary patency rate was significantly higher in the stent group (64.2%) than in the PTA group (31.3%, p=0.0001). TLR rates were 22.4% and 59.5%, respectively (p=0.0001). When provisional stent placement in the PTA arm was not considered as TLR and loss in patency, the differences prevailed between the study groups but were not significant (64.2% vs. 56.1% for primary patency, respectively; p=0.44). A significant improvement in ABI and Rutherford category was observed at 2 years in both groups. CONCLUSION In treatment of obstructive popliteal artery lesions, provisional stenting reveals equivalent patency in comparison to primary stenting. However, the 2-year results of this trial suggest the possibility of a shift toward higher patency rates in favor of primary stenting.

The Hypereosinophilic Syndromes in Childhood.

The hypereosinophilic syndromes are rare disorders in childhood and require extensive differential diagnostic considerations. In the last years the earlier "idiopathic HES" called syndromes could be differentiated into molecular biologically, immunophenotypically and clinically more characterized heterogeneous diseases with high therapeutic and prognostic relevance. Nowadays the term HES summarizes diseases, which go hand in hand with a local or systemic hypereosinophilia (HE) connected with an organ damage. Depending on the cause of the HE one differentiates primary/neoplastic HES (HESN) from secondary/reactive HES (HESR). The latter develops reactively in connection with allergies, parasitosis, medications, neoplasia or a clonal increase of T-lymphocytes among others. With HESN the HE results from a clonal increase of eosinophilic granulocytes. While for some subgroups of the HESN (among others FIP1L1-PDGFRA fusion gene) the administration of a tyrosine kinase inhibitor is a new and effective therapy option, glucocorticoids still represent the medication of first choice for many not PDGFRA associated variants. Different immunomodulatory drugs or cytostatic agents are necessary to allow dose reduction of glucocorticoids. The promising therapy with anti-IL-5 antibodies is still not approved in infancy, could however become a treatment option in the future. Due to the present lack of knowledge about the HES in infancy the establishment of a register should be aimed for the treatment of HES in infancy.

Does Full Wound Rupture following Median Pilonidal Closure Alter Long-Term Recurrence Rate?

OBJECTIVE The purpose of this study was to examine the recurrence rate of wound rupture in primary pilonidal sinus disease (PSD) after median closure. SUBJECTS AND METHODS A total of 583 patients from the German military cohort were interviewed. We compared the choice of surgical therapy, wound dehiscence (if present) and long-term recurrence-free survival for patients with primary open treatment, marsupialization and primary median treatment (closed vs. secondary open, respectively). Actuarial recurrence rate was determined using the Kaplan-Meier calculation with a follow-up of up to 20 years after primary PSD surgery. RESULTS Patients with excision followed by primary open wound treatment showed a significantly lower 5- than 10-year recurrence rate (8.3 vs. 11.2%) compared to the patients with primary midline closure (17.4 vs. 20.5%, p = 0.03). The 20-year recurrence rate was 28% in primary open wound treatment versus 44% in primary midline closure without wound rupture. In contrast to these findings, long-term recurrence rates following secondary open wound treatment (12.2% at 5 years vs. 17.1% at 10 years) tended to be higher (although not significantly, p = 0.57) compared to primary open treatment (8.3% at 5 years vs. 11.2% at 10 years). There was no statistical difference in long-term recurrence rates between secondary open and primary midline closure (p = 0.7). Hence, despite only a short wound closure time experienced before wound rupture, the patient does not fully benefit from an open wound treatment in terms of recurrence rate. CONCLUSION The postoperative pilonidal sinus wound rupture of primary midline closures did not significantly increase the 5- and 10-year long-term recurrence rates compared to uneventfully healing primary midline closures.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

Source apportionment and dynamic changes of carbonaceous aerosols during the haze bloom-decay process in China based on radiocarbon and organic molecular tracers

Fine carbonaceous aerosols (CAs) is the key factor influencing the currently filthy air in megacities in China, yet few studies simultaneously focus on the origins of different CAs species using specific and powerful source tracers. Here, we present a detailed source apportionment for various CAs fractions, including organic carbon (OC), water-soluble OC (WSOC), water-insoluble OC (WIOC), elemental carbon (EC) and secondary OC (SOC) in the largest cities of North (Beijing, BJ) and South China (Guangzhou, GZ), using the measurements of radiocarbon and anhydrosugars. Results show that non-fossil fuel sources such as biomass burning and biogenic emission make a significant contribution to the total CAs in Chinese megacities: 56±4 in BJ and 46±5% in GZ, respectively. The relative contributions of primary fossil carbon from coal and liquid petroleum combustions, primary non-fossil carbon and secondary organic carbon (SOC) to total carbon are 19, 28 and 54% in BJ, and 40, 15 and 46% in GZ, respectively. Non-fossil fuel sources account for 52 in BJ and 71% in GZ of SOC, respectively. These results suggest that biomass burning has a greater influence on regional particulate air pollution in North China than in South China. We observed an unabridged haze bloom-decay process in South China, which illustrates that both primary and secondary matter from fossil sources played a key role in the blooming phase of the pollution episode, while haze phase is predominantly driven by fossil-derived secondary organic matter and nitrate.

Situational adaptiveness of control orientation mediates relation between fixed-world view and youth well-being in three cultures

When proposing primary control (changing the world to fit self)/secondary control (changing self to fit the world) theory, Weisz et al. (1984) argued for the importance of the “serenity to accept the things I cannot change, the courage to change the things I can” (p. 967), and the wisdom to choose the right control strategy that fits the context. Although the dual processes of control theory generated hundreds of empirical studies, most of them focused on the dichotomy of PC and SC, with none of these tapped into the critical concept: individuals’ ability to know when to use what. This project addressed this issue by using scenario questions to study the impact of situationally adaptive control strategies on youth well-being. To understand the antecedents of youths’ preference for PC or SC, we also connected PCSC theory with Dweck’s implicit theory about the changeability of the world. We hypothesized that youths’ belief about the world’s changeability impacts how difficult it was for them to choose situationally adaptive control orientation, which then impacts their well-being. This study included adolescents and emerging adults between the ages of 18 and 28 years (Mean = 20.87 years) from the US (n = 98), China (n = 100), and Switzerland (n = 103). Participants answered a questionnaire including a measure of implicit theories about the fixedness of the external world, a scenario-based measure of control orientation, and several measures of well-being. Preliminary analyses of the scenario-based control orientation measures showed striking cross-cultural similarity of preferred control responses: while for three of the six scenarios primary control was the predominately chosen control response in all cultures, for the other three scenarios secondary control was the predominately chosen response. This suggested that youths across cultures are aware that some situations call for primary control, while others demand secondary control. We considered the control strategy winning the majority of the votes to be the strategy that is situationally adaptive. The results of a multi-group structural equation mediation model with the extent of belief in a fixed world as independent variable, the difficulties of carrying out the respective adaptive versus non-adaptive control responses as two mediating variables and the latent well-being variable as dependent variable showed a cross-culturally similar pattern of effects: a belief in a fixed world was significantly related to higher difficulties in carrying out the normative as well as the non-normative control response, but only the difficulty of carrying out the normative control response (be it primary control in situations where primary control is normative or secondary control in situations where secondary control is normative) was significantly related to a lower reported well-being (while the difficulty of carrying out the non-normative response was unrelated to well-being). While previous research focused on cross-cultural differences on the choice of PC or SC, this study shed light on the universal necessity of applying the right kind of control to fit the situation.

Sexual orientation and sexual behavior patterns: Evaluation of agreement and variation in a cohort of male, African American drug users in Houston, TX

Background. Sexual orientation and sexual behavior among men have shown disagreement in past studies. The term "on the down low" has been adopted by many to describe "straight" identifying men who have sex with men but do not inform their primary female partner. Methods. This secondary analysis of data collected from the "DASH Project---A Hepatitis B Vaccine Model for HIV Vaccine Trial in Drug Users," assessed sexual behavior patterns among African American drug-using men over time. Using a screener questionnaire to determine sexual orientation and sexual behavior of the men, the study specifically evaluated "straight" identified men who have sex with women only (MSW) to determine what factors were associated with sexual behavior variation to include men during follow-up. The Fisher's Exact Test was used to evaluate the factors. Results. Variation of sexual behavior was highest among "bisexual" identified men followed by "gay" identified men. Fifteen of the original 593 "straight" and MSW men had sexual behavior variation to include men. In the analysis of "straight" and MSW men with variation in sexual behavior compared to those who did not, living on the streets, greater number of sexual partners, trading sex for drugs, and trading sex for money were associated with sexual behavior variation (all p-values <0.01). Conclusions. The factors were only associated when considering the interview when the variation occurred. The same factors at screening were not predictive of sexual behavior variation in the future. Environmental factors, such as living situation, appear to play a role in sexual behavior variations in "straight" and MSW men. ^ Keywords. sexual behavior, sexual orientation, Fisher's Exact Test^

Chert intervals in DSDP and ODP sites (Table 1)

Radiolarian cherts in the Tethyan realm of Jurassic age were recently interpreted as resulting from high biosiliceous productivity along upwelling zones in subequatorial paleolatitudes the locations of which were confirmed by revised paleomagnetic estimates. However, the widespread occurrence of cherts in the Eocene suggests that cherts may not always be reliable proxies of latitude and upwelling zones. In a new survey of the global spatio-temporal distribution of Cenozoic cherts in Deep Sea Drilling Project (DSDP) and Ocean Drilling Program (ODP) sediment cores, we found that cherts occur most frequently in the Paleocene and early Eocene, with a peak in occurrences at ~50 Ma that is coincident with the time of highest bottom water temperatures of the early Eocene climatic optimum (EECO) when the global ocean was presumably characterized by reduced upwelling efficiency and biosiliceous productivity. Cherts occur less commonly during the subsequent Eocene global cooling trend. Primary paleoclimatic factors rather than secondary diagenetic processes seem therefore to control chert formation. This timing of peak Eocene chert occurrence, which is supported by detailed stratigraphic correlations, contradicts currently accepted models that involve an initial loading of large amounts of dissolved silica from enhanced weathering and/or volcanism in a supposedly sluggish ocean of the EECO, followed during the subsequent middle Eocene global cooling by more vigorous oceanic circulation and consequent upwelling that made this silica reservoir available for enhanced biosilicification, with the formation of chert as a result of biosilica transformation during diagenesis. Instead, we suggest that basin-basin fractionation by deep-sea circulation could have raised the concentration of EECO dissolved silica especially in the North Atlantic, where an alternative mode of silica burial involving widespread direct precipitation and/or absorption of silica by clay minerals could have been operative in order to maintain balance between silica input and output during the upwelling-deficient conditions of the EECO. Cherts may therefore not always be proxies of biosiliceous productivity associated with latitudinally focused upwelling zones.

(Table T1) Fluid inclusions in siltstone and sandstone grains from ODP Hole 210-1276A

Twenty samples of siltstones and sandstones were taken from Ocean Drilling Program Site 1276 during Leg 210 for fluid inclusion studies. With the exception of one sample of vein calcite, all inclusions were in quartz grains. The results of fluid-inclusion petrology and microthermometry indicate the presence of three fluid inclusion types (Types 1, 2, and 3). Type 1 fluid inclusions are two-phase (liquid + vapor) aqueous inclusions, and Type 2 inclusions are monophase fluid inclusions (liquid or vapor). These are common in all samples and are formed either as primary isolated inclusions or as secondary inclusions as trails along annealed fractures in the grain. Type 3 fluid inclusions are three-phase (liquid + vapor + solid) inclusions. Type 3 inclusions are rare and are observed as isolated inclusions or in a cluster with other types (i.e., Types 1 and 2). The predominant population throughout the different units sampled is two-phase (liquid + vapor) aqueous fluid inclusions (i.e., Type 1). The temperature of homogenization (TH) bivariate plots for Type 1 inclusions shows dominance throughout the hole of low- to medium-salinity fluids with minimum trapping temperatures between 150° and 400°C.

Improved Animal Tracking Algorithm using Distributed Kalman Filter-based Algortihms

Animal tracking has been addressed by different initiatives over the last two decades. Most of them rely on satellite connectivity on every single node and lack of energy-saving strategies. This paper presents several new contributions on the tracking of dynamic heterogeneous asynchronous networks (primary nodes with GPS and secondary nodes with a kinetic generator) motivated by the animal tracking paradigm with random transmissions. A simple approach based on connectivity and coverage intersection is compared with more sophisticated algorithms based on ad-hoc implementations of distributed Kalman-based filters that integrate measurement information using Consensus principles in order to provide enhanced accuracy. Several simulations varying the coverage range, the random behavior of the kinetic generator (modeled as a Poisson Process) and the periodic activation of GPS are included. In addition, this study is enhanced with HW developments and implementations on commercial off-the-shelf equipment which show the feasibility for performing these proposals on real hardware.