Common reservoirs for Penicillium marneffei infection in humans and rodents, China

Human penicilliosis marneffei is an emerging infectious disease caused by the fungus Penicillium marneffei. High prevalence of infection among bamboo rats of the genera Rhizomys and Cannomys suggest that these rodents are a key facet of the P. marneffei life cycle. We trapped bamboo rats during June 2004-July 2005 across Guangxi Province, China, and demonstrated 100% prevalence of infection. Multilocus genotypes show that P. marneffei isolates from humans are similar to those infecting rats and are in some cases identical. Comparison of our dataset with genotypes recovered from sites across Southeast Asia shows that the overriding component of genetic structure in P. marneffei is spatial, with humans containing a greater diversity of genotypes than rodents. Humans and bamboo rats are sampling an as-yet undiscovered common reservoir of infection, or bamboo rats are a vector for human infections by acting as amplifiers of infectious dispersal stages.     

Neighborhood social capital and individual health

Neighborhood social capital is increasingly considered to be an important determinant of an individual's health. Using data from the Netherlands we investigate the influence of neighborhood social capital on an individual's self-reported health, while accounting for other conditions of health on both the level of the neighborhood and the individual. We use national representative data ('The Housing and Living Survey', 2006) on the Netherlands with 61,235 respondents in 3273 neighborhoods. The cross-sectional data were combined with information provided by Statistics Netherlands on neighborhoods, i.e., the percentage of residents in the highest income quintile per neighborhood and the municipality's degree of urbanity. The association of neighborhood social capital with individual health was assessed by multilevel logistic regression analysis. Our results show that neighborhood social capital is positively associated with health. Interestingly, residents in urban neighborhoods benefit particularly from their neighborhood social capital.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Reasons and predictors of discontinuation of running after a running program for novice runners

Objectives

To determine the proportion of participants of a running program for novice runners that discontinued running and investigate the main reasons to discontinue and characteristics associated with discontinuation.

Prognosis and prognostic factors of running-related injuries in novice runners: A prospective cohort study

Objectives

To investigate the prognosis and possible prognostic factors of running-related injuries (RRIs) in novice runners.