OpenDocument v1.2 Relax NG Schema

This specification supersedes OASIS OpenDocument v1.1 [ODF11]. This specification consists of this document as well as the following documents, schemas and ontologies

Conversion of Mature Human β-Cells Into Glucagon-Producing α-Cells

Conversion of one terminally differentiated cell type into another (or transdifferentiation) usually requires the forced expression of key transcription factors. We examined the plasticity of human insulin-producing β-cells in a model of islet cell aggregate formation. Here, we show that primary human β-cells can undergo a conversion into glucagon-producing α-cells without introduction of any genetic modification. The process occurs within days as revealed by lentivirus-mediated β-cell lineage tracing. Converted cells are indistinguishable from native α-cells based on ultrastructural morphology and maintain their α-cell phenotype after transplantation in vivo. Transition of β-cells into α-cells occurs after β-cell degranulation and is characterized by the presence of β-cell–specific transcription factors Pdx1 and Nkx6.1 in glucagon+ cells. Finally, we show that lentivirus-mediated knockdown of Arx, a determinant of the α-cell lineage, inhibits the conversion. Our findings reveal an unknown plasticity of human adult endocrine cells that can be modulated. This endocrine cell plasticity could have implications for islet development, (patho)physiology, and regeneration

Detectable Clonal Mosaicism from Birth to Old Age and its Relationship to Cancer

Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5–10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rises rapidly to 2–3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions that pinpoint the locations of genes previously associated with hematological cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer prior to DNA sampling, those without a prior diagnosis have an estimated 10-fold higher risk of a subsequent hematological cancer (95% confidence interval = 6–18)

The stranding anomaly as population indicator: the case of Harbour Porpoise <i>Phocoena phocoena</i> in North-Western Europe

Ecological indicators for monitoring strategies are expected to combine three major characteristics: ecological significance, statistical credibility, and cost-effectiveness. Strategies based on stranding networks rank highly in cost-effectiveness, but their ecological significance and statistical credibility are disputed. Our present goal is to improve the value of stranding data as population indicator as part of monitoring strategies by constructing the spatial and temporal null hypothesis for strandings. The null hypothesis is defined as: small cetacean distribution and mortality are uniform in space and constant in time. We used a drift model to map stranding probabilities and predict stranding patterns of cetacean carcasses under H-0 across the North Sea, the Channel and the Bay of Biscay, for the period 1990-2009. As the most common cetacean occurring in this area, we chose the harbour porpoise <i>Phocoena phocoena</i> for our modelling. The difference between these strandings expected under H-0 and observed strandings is defined as the stranding anomaly. It constituted the stranding data series corrected for drift conditions. Seasonal decomposition of stranding anomaly suggested that drift conditions did not explain observed seasonal variations of porpoise strandings. Long-term stranding anomalies increased first in the southern North Sea, the Channel and Bay of Biscay coasts, and finally the eastern North Sea. The hypothesis of changes in porpoise distribution was consistent with local visual surveys, mostly SCANS surveys (1994 and 2005). This new indicator could be applied to cetacean populations across the world and more widely to marine megafauna

Total Synthesis of Kalimantacin A

The kalimantacins make up a family of hybrid polyketide-nonribosomal peptide-derived natural products that display potent and selective antibiotic activity against multidrug resistant strains of Staphylococcus aureus. Herein, we report the first total synthesis of kalimantacin A, in which three fragments are prepared and then united via Sonogashira and amide couplings. The enantioselective synthetic approach is convergent, unlocking routes to further kalimantacins and analogues for structure-activity relationship studies and clinical evaluation.status: publishe

Counting hard-to-count populations: the network scale-up method for public health

Estimating sizes of hidden or hard-to-reach populations is an important problem in public health. For example, estimates of the sizes of populations at highest risk for HIV and AIDS are needed for designing, evaluating and allocating funding for treatment and prevention programmes. A promising approach to size estimation, relatively new to public health, is the network scale-up method (NSUM), involving two steps: estimating the personal network size of the members of a random sample of a total population and, with this information, estimating the number of members of a hidden subpopulation of the total population. We describe the method, including two approaches to estimating personal network sizes (summation and known population). We discuss the strengths and weaknesses of each approach and provide examples of international applications of the NSUM in public health. We conclude with recommendations for future research and evaluation

Hip and groin injury is the most common non-time-loss injury in female amateur football

Purpose: Hip and groin injuries in football are problematic due to their high incidence and risk of chronicity and recurrence. The use of only time-loss injury definitions may underestimate the burden of hip and groin injuries. Little is known about hip and groin injury epidemiology in female football. The first aim of this study was to examine the within-season (2014–2015) prevalence of total injury with and without time-loss in female amateur football players. The second aim was to study the within-season and preseason (2015–2016) prevalence of hip/groin injuries with and without time-loss. The third aim was to study the association between the duration of hip and groin injury in the 2014–2015 season and the severity of hip/groin problems during the 2015–2016 preseason. Methods: During the preseason, 434 Dutch female amateur football players completed an online questionnaire based on the previous season and current preseason. The hip and groin outcome score (HAGOS) was used to assess the severity of hip and groin injuries. Results: The hip/groin (17%), knee (14%), and ankle (12%) were the most frequent non-time-loss injury locations. The ankle (22%), knee (18%), hamstring (11%), thigh (10%), and hip/groin (9%) were the most common time-loss injury locations. The previous season prevalence of total injury was 93%, of which non-time-loss injury was 63% and time-loss injury was 37%. The prevalence of hip/groin injury was 40%, non-time-loss hip/groin injury was 36% and time-loss hip/groin injury was 11%. The preseason prevalence of hip/groin injury was 27%, non-time-loss hip/groin injury was 25%, and time-loss hip/groin injury was 4%. Players with longstanding hip/groin injury (> 28 days) in the previous season had lower HAGOS scores at the next preseason than players with short-term (1–7 days) or no hip/groin injury (p < 0.001). From all players with hip/groin injury from the previous season, 52% also sustained hip/groin injury in the following preseason, of which 73% were recurrent and 27% were chronic hip/groin injuries. Conclusion: Injury risk, and especially non-time-loss hip and groin injury risk, is high in female amateur football. Three-quarters of the players with longstanding hip and groin injuries in the previous season have residual problems at the start of the following season. Level of evidence: II

Concurrent validity and test-retest reliability of the Virtual Peg Insertion Test to quantify upper limb function in patients with chronic stroke

Background: Measuring arm and hand function of the affected side is vital in stroke rehabilitation. Therefore, the Virtual Peg Insertion Test (VPIT), an assessment combining virtual reality and haptic feedback during a goal-oriented task derived from the Nine Hole Peg Test (NHPT), was developed. This study aimed to evaluate (1) the concurrent validity of key outcome measures of the VPIT, namely the execution time and the number of dropped pegs, with the NHPT and Box and Block Test (BBT), and (2) the test-retest-reliability of these parameters together with the VPIT's additional kinetic and kinematic parameters in patients with chronic stroke. The three tests were administered on 31 chronic patients with stroke in one session (concurrent validity), and the VPIT was retested in a second session 3-7 days later (test-retest reliability). Spearman rank correlation coefficients (rho) were calculated for assessing concurrent validity, and intraclass correlation coefficients (ICCs) were used to determine relative reliability. Bland-Altman plots were drawn and the smallest detectable difference (SDD) was calculated to examine absolute reliability. Results: For the 31 included patients, 11 were able to perform the VPIT solely via use of their affected arm, whereas 20 patients also had to utilize support from their unaffected arm. For n = 31, the VPIT showed low correlations with the NHPT (rho = 0.31 for time (T-ex[s]); rho = 0.21 for number of dropped pegs (N-dp)) and BBT (rho = -0.23 for number of transported cubes (N-tc); rho = -0.12 for number of dropped cubes (N-dc)). The test-retest reliability for the parameters Tex[s], mean grasping force (F(g)go[N]), number of zero-crossings (N(zc[1/s)go/return) and mean collision force (F-cmean[N]) were good to high, with ICCs ranging from 0.83 to 0.94. Fair reliability could be found for F(g)return (ICC = 0.75) and trajectory error (E(traj)go[cm]) (0.70). Poor reliability was measured for E(traj)return[cm] (0.67) and N-dp (0.58). The SDDs were: T-ex = 70.2 s, N-dp = 0.4 pegs; F(g)go/return = 3.5/1.2 Newton; N(zc[1/s])go/return = 0.2/1.8 zero-crossings; E(traj)go/return = 3.5/1.2 Newton; N(zc[1/s])go/return = 0.2/1.8 zero-crossings; E(traj)go/return = 0.5/0.8 cm; F-cmean = 0.7 Newton. Conclusions: The VPIT is a promising upper limb function assessment for patients with stroke requiring other components of upper limb motor performance than the NHPT and BBT. The high intra-subject variation indicated that it is a demanding test for this stroke sample, which necessitates a thorough introduction to this assessment. Once familiar, the VPIT provides more objective and comprehensive measurements of upper limb function than conventional, non-computerized hand assessments