Oncogenic Hypophosphatemic Osteomalacia Associated with a Giant Cell Tumour of a Tendon Sheath

We report a case of oncogenic hypophosphatemic osteomalacia, a rare form of osteomalacia, secondary to a diffuse giant cell tumour of tendon sheath. Possible pathogenic factors are discussed in the light of previously described clinical and experimental observations

MOIRCS Deep Survey IV: Evolution of Galaxy Stellar Mass Function Back to z ~ 3

We use very deep near-infrared (NIR) imaging data obtained in MOIRCS Deep Survey (MODS) to investigate the evolution of the galaxy stellar mass function back to z~3. The MODS data reach J=24.2, H=23.1, K=23.1 (5sigma, Vega magnitude) over 103 arcmin^2 (wide) and J=25.1, H=23.7, K=24.1 over 28 arcmin^2 (deep) in the GOODS-North region. The wide and very deep NIR data allow us to measure the number density of galaxies down to low stellar mass (10^9-10^10 Msun) even at high redshift with high statistical accuracy. The normalization of the mass function decreases with redshift and the integrated stellar mass density becomes ~ 8-18% of the local value at z~2 and ~ 4-9% at z~3, which are consistent with results of previous studies in general fields. Furthermore, we found that the low-mass slope becomes steeper with redshift from alpha ~- 1.3 at z~1 to alpha ~- 1.6 at z~3, and that the evolution of the number density of low-mass (10^9-10^10 Msun) galaxies is weaker than that of M* (~10^11 Msun) galaxies. This indicates that the contribution of low-mass galaxies to the total stellar mass density has been significant at high redshift. The steepening of the low-mass slope with redshift is opposite trend expected from the stellar mass dependence of the specific star formation rate reported in previous studies. The present result suggests that the hierarchical merging process overwhelmed the effect of the stellar mass growth by star formation and was very important for the stellar mass assembly of these galaxies at 1<~z<~3.Comment: 21 pages, 18 figures, accepted for publication in Ap

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

Background & Aims: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH‐2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha‐fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post‐hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). Methods: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH‐2. Kaplan‐Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression‐free survival (PFS), time to progression (TTP) and patient‐reported outcomes (Functional Hepatobiliary System Index‐8 [FHSI‐8] score). Results: A total of 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581‐0.975), ≥65 to <75 years (0.602; 0.419‐0.866) and ≥75 years (0.709; 0.420‐1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI‐8 with ramucirumab was observed in all subgroups. Conclusions: In this post‐hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75 years

The relation between Lyman-alpha absorbers and gas--rich galaxies in the local universe

We use high-resolution hydrodynamical simulations to investigate the spatial correlation between weak (N(HI) <10^{15} cm^{-2}) Ly-alpha absorbers and gas-rich galaxies in the local universe. We confirm that Ly-alpha absorbers are preferentially expected near gas-rich galaxies and that the degree of correlation increases with the column density of the absorber. The real-space galaxy auto-correlation is stronger than the cross-correlation (correlation lengths r_{0,gg}=3.1 \pm 0.1 Mpc/h and r_{0,ag}=1.4 \pm 0.1 Mpc/h, respectively), in contrast with the recent results of Ryan-Weber (2006, RW06), and the auto-correlation of absorbers is very weak. These results are robust to the presence of strong galactic winds in the hydrodynamical simulations. In redshift-space a further mismatch arises since at small separations the distortion pattern of the simulated galaxy-absorber cross-correlation function is different from the one measured by RW06. However, when sampling the intergalactic medium along a limited number of lines-of-sight, as in the real data, uncertainties in the cross correlation estimates are large enough to account for these discrepancies. Our analysis suggests that the statistical significance of difference between the cross-correlation and auto-correlation signal in current datasets is ~ 1-sigma only.Comment: 11+ pages, 9 figures. MNRAS in pres

Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

Background & Aims: The albumin-bilirubin (ALBI) grade/score is derived from a validated nomogram to objectively assess prognosis and liver function in patients with hepatocellular carcinoma (HCC). In this post hoc analysis, we assessed prognosis in terms of survival by baseline ALBI grade and monitored liver function during treatment with ramucirumab or placebo using the ALBI score in patients with advanced HCC. Methods: Patients with advanced HCC, Child-Pugh class A with prior sorafenib treatment were randomised in REACH trials to receive ramucirumab 8 mg/kg or placebo every 2weeks. Datawere analysed by trial and as a meta-analysis of individual patientlevel data (pooled population) from REACH (alpha-fetoprotein>− 400 ng/ml) and REACH-2. Patients from REACHwith Child-Pugh class Bwere analysed as a separate cohort. The ALBI grades and scoreswere calculated at baseline and before each treatment cycle. Results: Baseline characteristics by ALBI grade were balanced between treatment arms among patients in the pooled population (ALBI-1, n = 231; ALBI-2, n = 296; ALBI-3, n = 7). Baseline ALBI grade was prognostic for overall survival (OS; ALBI grade 2 vs. 1; hazard ratio [HR]: 1.38 [1.13-1.69]), after adjusting for other significant prognostic factors. Mean ALBI scores remained stable in both treatment arms compared with baseline and were unaffected by baseline ALBI grade, macrovascular invasion, tumour response, geographical region, or prior locoregional therapy. Baseline ALBI grades 2 and 3 were associated with increased incidence of liver-specific adverse events and discontinuation rates in both treatments. Ramucirumab improved OS in patients with baseline ALBI grade 1 (HR 0.605 [0.445-0.824]) and ALBI grade 2 (HR 0.814 [0.630-1.051]. Conclusions: Compared with placebo, ramucirumab did not negatively impact liver function and improved survival irrespective of baseline ALBI grade

The influence of melt infiltration on the Li and Mg isotopic composition of the Horoman Peridotite Massif

We have analysed the Li and Mg isotope ratios of a suite of samples from the Horoman peridotite massif. Our results show that most Li and all Mg isotopic compositions of the Horoman peridotites are constant over 100 metres of continuous outcrop, yielding values for pristine mantle of δ7Li = 3.8 ± 1.4 ‰ (2SD, n = 9), δ25Mg = -0.12 ± 0.02 ‰ and δ26Mg = -0.23 ± 0.04 ‰ (2SD, n = 17), in keeping with values for undisturbed mantle xenoliths. However, there are also some anomalously low δ7Li values (-0.2 to 1.6 ‰), which coincide with locations that show enrichment of incompatible elements, indicative of the prior passage of small degree melts. We suggest Li diffused from the infiltrating melts with high [Li] into the low [Li] minerals and kinetically fractionated 7Li/6Li as a result. Continued diffusion after the melt flow had ceased would have resulted in the disappearance of this isotopically light signature in less than 15 Ma. In order to preserve this feature, the melt infiltration must have been a late stage event and the massif must have subsequently cooled over a maximum of ∼0.3 Ma from peak temperature (950°C, assuming the melts are hydrous) to Li closure temperature (700°C), likely during emplacement. The constant δ26Mg values of Horoman peridotites suggest that chemical potential gradients caused by melt infiltration were insufficient to drive associated δ26Mg fractionation greater than our external precision of 0.03 ‰

Engaging Struggling Adolescent Readers to Improve Reading Skills

This study examined the efficacy of a supplemental, multicomponent adolescent reading intervention for middle school students who scored below proficient on a state literacy assessment. Using a within-school experimental design, the authors randomly assigned 483 students in grades 6–8 to a business-as-usual control condition or to the Strategic Adolescent Reading Intervention (STARI), a supplemental reading program involving instruction to support word-reading skills, fluency, vocabulary, and comprehension, and peer talk to promote reading engagement and comprehension. The authors assessed behavioral engagement by measuring how much of the STARI curricular activities students completed during an academic school year, and collected intervention teachers' ratings of their students' reading engagement. STARI students outperformed control students on measures of word recognition (Cohen's d = 0.20), efficiency of basic reading comprehension (Cohen's d = 0.21), and morphological awareness (Cohen's d = 0.18). Reading engagement in its behavioral form, as measured by students' participation and involvement in the STARI curriculum, mediated the treatment effects on each of these three posttest outcomes. Intervention teachers' ratings of their students' emotional and cognitive engagement explained unique variance on reading posttests. Findings from this study support the hypothesis that (a) behavioral engagement fosters struggling adolescents' reading growth, and (b) teachers' perceptions of their students' emotional and cognitive engagement further contribute to reading competence

Examples of holistic good practices in promoting and protecting mental health in the workplace: current and future challenges

Background: While attention has been paid to physical risks in the work environment and the promotion of individual employee health, mental health protection and promotion have received much less focus. Psychosocial risk management has not yet been fully incorporated in such efforts. This paper presents good practices in promoting mental health in the workplace in line with World Health Organization (WHO) guidance by identifying barriers, opportunities, and the way forward in this area. Methods: Semistructured interviews were conducted with 17 experts who were selected on the basis of their knowledge and expertise in relation to good practice identified tools. Interviewees were asked to evaluate the approaches on the basis of the WHO model for healthy workplaces. Results: The examples of good practice for Workplace Mental Health Promotion (WMHP) are in line with the principles and the five keys of the WHO model. They support the third objective of the WHO comprehensive mental health action plan 2013e2020 for multisectoral implementation of WMHP strategies. Examples of good practice include the engagement of all stakeholders and representatives, science-driven practice, dissemination of good practice, continual improvement, and evaluation. Actions to inform policies/legislation, promote education on psychosocial risks, and provide better evidence were suggested for higher WMHP success. Conclusion: The study identified commonalities in good practice approaches in different countries and stressed the importance of a strong policy and enforcement framework as well as organizational responsibility for WMHP. For progress to be achieved in this area, a holistic and multidisciplinary approach was unanimously suggested as a way to successful implementation

pitx2 Deficiency Results in Abnormal Ocular and Craniofacial Development in Zebrafish

Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2ex4/5 splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition) helix of the DNA-binding homeodomain. The morphological phenotype of pitx2ex4/5 morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6–8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2ex4/5 morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates