Multiple paternity in superfetatious live-bearing fishes.

Superfetation, the ability to carry several overlapping broods at different developmental stages, has evolved independently multiple times within the live-bearing fish family Poeciliidae. Even though superfetation is widespread among poeciliids, its evolutionary advantages remain unclear. Theory predicts that superfetation should increase polyandry by increasing the probability that temporally overlapping broods are fertilized by different fathers. Here, we test this key prediction in two poeciliid species that each carry two temporally overlapping broods: Poeciliopsis retropinna and P. turrubarensis. We collected 25 females per species from freshwater streams in South-Eastern Costa Rica and assessed multiple paternity by genotyping all their embryos (420 embryos for P. retropinna; 788 embryos for P. turrubarensis) using existing and newly developed microsatellite markers. We observed a high frequency of unique sires in the simultaneous, temporally overlapping broods in P. retropinna (in 56% of the pregnant females) and P. turrubarensis (79%). We found that the mean number of sires within females was higher than the number of sires within the separate broods (2.92 sires within mothers vs. 2.36 within separate broods in P. retropinna; and 3.40 vs 2.56 in P. turrubarensis). We further observed that there were significant differences in the proportion of offspring sired by each male in 42% of pregnant female P. retropinna and 65% of female P. turrubarensis; however, this significance applied to only 9% and 46% of the individual broods in P. retropinna and P. turrubarensis, respectively, suggesting that the unequal reproductive success of sires (i.e. reproductive skew) mostly originated from differences in paternal contribution between, rather than within broods. Together, these findings tentatively suggest that superfetation may promote polyandry and reproductive skew in live-bearing fishes

Frontotemporal Dementia: A Clinical Review.

Frontotemporal dementias are a clinically, neuroanatomically, and pathologically diverse group of diseases that collectively constitute an important cause of young-onset dementia. Clinically, frontotemporal dementias characteristically strike capacities that define us as individuals, presenting broadly as disorders of social behavior or language. Neurobiologically, these diseases can be regarded as "molecular nexopathies," a paradigm for selective targeting and destruction of brain networks by pathogenic proteins. Mutations in three major genes collectively account for a substantial proportion of behavioral presentations, with far-reaching implications for the lives of families but also potential opportunities for presymptomatic diagnosis and intervention. Predicting molecular pathology from clinical and radiological phenotypes remains challenging; however, certain patterns have been identified, and genetically mediated forms of frontotemporal dementia have spearheaded this enterprise. Here we present a clinical roadmap for diagnosis and assessment of the frontotemporal dementias, motivated by our emerging understanding of the mechanisms by which pathogenic protein effects at the cellular level translate to abnormal neural network physiology and ultimately, complex clinical symptoms. We conclude by outlining principles of management and prospects for disease modification

The TOPGAME-study: effectiveness of extracorporeal shockwave therapy in jumping athletes with patellar tendinopathy. Design of a randomised controlled trial

BACKGROUND: Patellar tendinopathy is a major problem for many athletes, especially those involved in jumping activities. Despite its frequency and negative impact on athletic careers, no evidence-based guidelines for management of this overuse injury exist. Since functional outcomes of conservative and surgical treatments remain suboptimal, new diagnostic and therapeutic strategies have to be developed and evaluated. Extracorporeal shockwave therapy (ESWT) appears to be a promising treatment in patients with chronic patellar tendinopathy. ESWT is most often applied after the known conservative treatments have failed. However, its effectiveness as primary therapy has not been studied in athletes who keep playing sports despite having patellar tendon pain. The aim of this study is to determine the effectiveness of ESWT in athletes with patellar tendinopathy who are still in training and competition. METHODS/DESIGN: The TOPGAME-study (Tendinopathy of Patella Groningen Amsterdam Maastricht ESWT) is a multicentre two-armed randomised controlled trial with blinded participants and outcome assessors, in which the effectiveness of patient-guided focussed ESWT treatment (compared to placebo ESWT) on pain reduction and recovery of function in athletes with patellar tendinopathy will be investigated. Participants are volleyball, handball and basketball players with symptoms of patellar tendinopathy for a minimum of 3 to a maximum duration of 12 months who are still able to train and compete. The intervention group receives three patient-guided focussed medium-energy density ESWT treatments without local anaesthesia at a weekly interval in the first half of the competition. The control group receives placebo treatment. The follow-up measurements take place 1, 12 and 22 weeks after the final ESWT or placebo treatment, when athletes are still in competition. Primary outcome measure is the VISA-P (Victorian Institute of Sport Assessment - patella) score. Data with regard to pain during function tests (jump tests and single-leg decline squat) and ultrasound characteristics are also collected. During the follow-up period participants also register pain, symptoms, sports participation, side effects of treatment and additional medical consumption in an internet-based diary. DISCUSSION: The TOPGAME-study is the first RCT to study the effectiveness of patient-guided ESWT in athletes with patellar tendinopathy who are still in training and competition. TRIAL REGISTRATION: Trial registration number NTR1408

Validity and Reliability of the Strengths and Difficulties Questionnaire in 5–6 Year Olds: Differences by Gender or by Parental Education?

Introduction: The Strengths and Difficulties Questionnaire (SDQ) is a relatively short instrument developed to detect psychosocial problems in children aged 3-16 years. It addresses four dimensions: emotional problems, conduct problems, hyperactivity/inattention problems, peer problems that count up to the total difficulties score, and a fifth dimension; prosocial behaviour. The validity and reliability of the SDQ has not been fully investigated in younger age groups. Therefore, this study assesses the validity and reliability of the parent and teacher versions of the SDQ in children aged 5-6 years in the total sample, and in subgroups according to child gender and parental education level. Methods: The SDQ was administered as part of the Dutch regularly provided preventive health check for children aged 5-6 years. Parents provided information on 4750 children and teachers on 4516 children. Results: Factor analyses of the parent and teacher SDQ confirmed that the original five scales were present (parent RMSEA = 0.05; teacher RMSEA = 0.07). Interrater correlations between parents and teachers were small (ICCs of 0.21-0.44) but comparable to what is generally found for psychosocial problem assessments in children. These correlations were larger for males than for females. Cronbach's alphas for the total difficulties score were 0.77 for the parent SDQ and 0.81 for the teacher SDQ. Four of the subscales on the parent SDQ and two of the subscales on the teacher SDQ had an alpha <0.70. Alphas were generally higher for male children and for low parental education level. Discussion: The validity and reliability of the total difficulties score of the parent and teacher SDQ are satisfactory in all groups by informant, child gender, and parental education level. Our results support the use of the SDQ in younger age groups. However, some subscales are less reliable and we recommend only to use the total difficulties score for screening purposes

Superconformal Flavor Simplified

A simple explanation of the flavor hierarchies can arise if matter fields interact with a conformal sector and different generations have different anomalous dimensions under the CFT. However, in the original study by Nelson and Strassler many supersymmetric models of this type were considered to be 'incalculable' because the R-charges were not sufficiently constrained by the superpotential. We point out that nearly all such models are calculable with the use of a-maximization. Utilizing this, we construct the simplest vector-like flavor models and discuss their viability. A significant constraint on these models comes from requiring that the visible gauge couplings remain perturbative throughout the conformal window needed to generate the hierarchies. However, we find that there is a small class of simple flavor models that can evade this bound.Comment: 43 pages, 1 figure; V3: small corrections and clarifications, references adde

The complete mitochondrial genome of the citrus red mite Panonychus citri (Acari: Tetranychidae): high genome rearrangement and extremely truncated tRNAs

<p>Abstract</p> <p>Background</p> <p>The family Tetranychidae (Chelicerata: Acari) includes ~1200 species, many of which are of agronomic importance. To date, mitochondrial genomes of only two Tetranychidae species have been sequenced, and it has been found that these two mitochondrial genomes are characterized by many unusual features in genome organization and structure such as gene order and nucleotide frequency. The scarcity of available sequence data has greatly impeded evolutionary studies in Acari (mites and ticks). Information on Tetranychidae mitochondrial genomes is quite important for phylogenetic evaluation and population genetics, as well as the molecular evolution of functional genes such as acaricide-resistance genes. In this study, we sequenced the complete mitochondrial genome of <it>Panonychus citri </it>(Family Tetranychidae), a worldwide citrus pest, and provide a comparison to other Acari.</p> <p>Results</p> <p>The mitochondrial genome of <it>P. citri </it>is a typical circular molecule of 13,077 bp, and contains the complete set of 37 genes that are usually found in metazoans. This is the smallest mitochondrial genome within all sequenced Acari and other Chelicerata, primarily due to the significant size reduction of protein coding genes (PCGs), a large rRNA gene, and the A + T-rich region. The mitochondrial gene order for <it>P. citri </it>is the same as those for <it>P. ulmi </it>and <it>Tetranychus urticae</it>, but distinctly different from other Acari by a series of gene translocations and/or inversions. The majority of the <it>P. citri </it>mitochondrial genome has a high A + T content (85.28%), which is also reflected by AT-rich codons being used more frequently, but exhibits a positive GC-skew (0.03). The Acari mitochondrial <it>nad1 </it>exhibits a faster amino acid substitution rate than other genes, and the variation of nucleotide substitution patterns of PCGs is significantly correlated with the G + C content. Most tRNA genes of <it>P. citri </it>are extremely truncated and atypical (44-65, 54.1 ± 4.1 bp), lacking either the T- or D-arm, as found in <it>P. ulmi</it>, <it>T. urticae</it>, and other Acariform mites.</p> <p>Conclusions</p> <p>The <it>P. citri </it>mitochondrial gene order is markedly different from those of other chelicerates, but is conserved within the family Tetranychidae indicating that high rearrangements have occurred after Tetranychidae diverged from other Acari. Comparative analyses suggest that the genome size, gene order, gene content, codon usage, and base composition are strongly variable among Acari mitochondrial genomes. While extremely small and unusual tRNA genes seem to be common for Acariform mites, further experimental evidence is needed.</p

A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

<p>Abstract</p> <p>Background</p> <p>Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.</p> <p>Methods</p> <p>The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.</p> <p>Discussion</p> <p>The DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatric cancer patients as well as long-term survivors of childhood cancer. Other investigators planning to conduct large cohort studies on late effects may encounter similar challenges as those encountered during this study. The solutions to these challenges described in this paper may be useful to these investigators.</p> <p>Trial registration</p> <p>NTR2922; <url>http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922</url></p

The functional neuroanatomy of emotion processing in frontotemporal dementias

This is a pre-copyedited, author-produced version of an article accepted for publication in Brain following peer review. The version of record: Charles R Marshall, Christopher J D Hardy, Lucy L Russell et al., The functional neuroanatomy of emotion processing in frontotemporal dementias, Brain, awz204, is available online at: https://doi.org/10.1093/brain/awz204Brain Research TrustAlzheimer’s SocietyLeonard Wolfson Experimental Neurology CentreMedical Research Council UKNIHR UCLH Biomedical Research Centr