Extending Recovery of the Primordial Matter Power Spectrum

The shape of the primordial matter power spectrum Plin(k) encodes critical information on cosmological parameters. At large scales, the observable galaxy power spectrum Pobs(k) is expected to follow the shape of Plin(k), but on smaller scales the effects of nonlinearity and galaxy bias make the ratio Pobs(k)/Plin(k) scale-dependent. We develop a method that can extend the dynamic range of the Plin(k) recovery by incorporating constraints on the galaxy halo occupation distribution (HOD) from the projected galaxy correlation function wp. We devise an analytic model to calculate Pobs(k) in real-space and redshift-space. Once HOD parameters are determined by matching wp for a given cosmological model, galaxy bias is completely specified, and our analytic model predicts both the shape and normalization of Pobs(k). Applying our method to SDSS main galaxy samples, we find that the real-space Pobs(k) follows the shape of the nonlinear matter power spectrum at the 1-2% level up to k=0.2 h/Mpc. When we apply our method to SDSS LRG samples, the linear bias approximation is accurate to 5% at k<0.08 h/Mpc, but the scale-dependence of LRG bias prevents the use of linear theory at k>0.08 h/Mpc. Our HOD model prediction is in good agreement with the recent SDSS LRG Pobs(k) measurements at all measured scales (k<0.2 h/Mpc), naturally explaining the shape of Pobs(k). The "Q-model" prescription is a poor description of galaxy bias for the LRG samples, and it can lead to biased cosmological parameter estimates when measurements at k>0.1 h/Mpc are included in the analysis. We quantify the potential bias and constraints on cosmological parameters that arise from applying linear theory and Q-model fitting, and we demonstrate the utility of HOD modeling of future high precision measurements of Pobs(k) on quasi-linear scales.Comment: 19 pages, 15 figures, submitted to The Astrophysical Journa

Cosmological Constraints from Galaxy Clustering and the Mass-to-Number Ratio of Galaxy Clusters

We place constraints on the average density (Omega_m) and clustering amplitude (sigma_8) of matter using a combination of two measurements from the Sloan Digital Sky Survey: the galaxy two-point correlation function, w_p, and the mass-to-galaxy-number ratio within galaxy clusters, M/N, analogous to cluster M/L ratios. Our w_p measurements are obtained from DR7 while the sample of clusters is the maxBCG sample, with cluster masses derived from weak gravitational lensing. We construct non-linear galaxy bias models using the Halo Occupation Distribution (HOD) to fit both w_p and M/N for different cosmological parameters. HOD models that match the same two-point clustering predict different numbers of galaxies in massive halos when Omega_m or sigma_8 is varied, thereby breaking the degeneracy between cosmology and bias. We demonstrate that this technique yields constraints that are consistent and competitive with current results from cluster abundance studies, even though this technique does not use abundance information. Using w_p and M/N alone, we find Omega_m^0.5*sigma_8=0.465+/-0.026, with individual constraints of Omega_m=0.29+/-0.03 and sigma_8=0.85+/-0.06. Combined with current CMB data, these constraints are Omega_m=0.290+/-0.016 and sigma_8=0.826+/-0.020. All errors are 1-sigma. The systematic uncertainties that the M/N technique are most sensitive to are the amplitude of the bias function of dark matter halos and the possibility of redshift evolution between the SDSS Main sample and the maxBCG sample. Our derived constraints are insensitive to the current level of uncertainties in the halo mass function and in the mass-richness relation of clusters and its scatter, making the M/N technique complementary to cluster abundances as a method for constraining cosmology with future galaxy surveys.Comment: 23 pages, submitted to Ap

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

Background: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number: NCT02184195

Validity of physical activity monitors for assessing lower intensity activity in adults

Background: Accelerometers can provide accurate estimates of moderate-to-vigorous physical activity (MVPA). However, one of the limitations of these instruments is the inability to capture light activity within an acceptable range of error. The purpose of the present study was to determine the validity of different activity monitors for estimating energy expenditure (EE) of light intensity, semi-structured activities. Methods: Forty healthy participants wore a SenseWear Pro3 Armband (SWA, v.6.1), the SenseWear Mini, the Actiheart, ActiGraph, and ActivPAL monitors, while being monitored with a portable indirect calorimetry (IC). Participants engaged in a variety of low intensity activities but no formalized scripts or protocols were used during these periods. Results: The Mini and SWA overestimated total EE on average by 1.0% and 4.0%, respectively, while the AH, the GT3X, and the AP underestimated total EE on average by 7.8%, 25.5%, and 22.2%, respectively. The pattern-recognition monitors yielded non-significant differences in EE estimates during the semi-structured period (p = 0.66, p = 0.27, and p = 0.21 for the Mini, SWA, and AH, respectively). Conclusions: The SenseWear Mini provided more accurate estimates of EE during light to moderate intensity semi-structured activities compared to other activity monitors. This monitor should be considered when there is interest in tracking low intensity activities in groups of individuals.This research was funded by a grant from Bodymedia Inc. awarded to Dr. Greg Welk

An overview of the cutaneous porphyrias

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin–haem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014

Recent Innovations & Daily Problems. A new prosthesis in inguinal hernia repair:preliminary results of a pilot study.

Introduction: Elective surgery for inguinal hernia is affected by very low mortality « 1 per 10000 operation); in contrast, when surgery is carried out for complicated inguinal hernia, risks of postoperative complication are higher. TAPP is a world-wide accepted surgical practice in the treatment of elective bilateral or recurrent inguinal hernia, above all in young patients. Few exploratory studies were published on laparoscopic approach in the treatment of urgent complicated inguinal hernia. Aim of this study was to analyze feasibility (operative time, conversion rate), safety (postoperative morbidity, length of hospital stay) and quality of life (acute and chronic pain, return to work) of trans-abdominal pre-peritoneal laparoscopic hernia repair in acute incarcerated inguinal hernia. Rationale of laparoscopic trans-abdominal approach is the easier hernia reduction under vision and a better exploration of the abdominal cavity. Methods: from September 2012 to September 2013, 15 consecutive patients admitted in emergency at the Division of General Surgery of University "Sapienza", Polo Pontino, for acute incarcerated inguinal hernia were submitted to TAPP using 3 trocars (1 of 10 mm and 2 of 5mm) and polyester prosthesis fixed by fibrin glue. Exclusion criteria for laparoscopic approach were age III, previous abdominal surgery, signs of strangulated hernia. All of them were evaluated for operative time, conversion rate, postoperative morbidity, organ resection or other surgery required. All patients were scored for pain by Visual Analogic Scale (VAS) during postoperative in hospital stay at 7 days, 1,6 and 12 months after surgery. Results: median follow-up was 16 months and 12 as minimum. In all cases reduction of hernia was always possible and none conversion to open surgery was recorded, median operative time was 89 minutes (55-137 as range), omental resection was carried out in one patient (6,6%), no other organ resections needed, whereas contralateral hernia was diagnosed and repaired at the same time in 4 patients (26,6%). No major complications were observed, median blood loss was 100 ml, minor morbidity was contained to 18% represented by fever and wound infection of surgical umbilical scar. Median in hospital stay was 1,5 days with 1-5 days as range. Postoperative median acute pain, measured by visual analogic scale (VAS), was 2 (range:0-4), none patient referred any pain during follow-up. Median time of return to work was 6,5 days, ranged between 3 to 15 days. Patients' compliance to treatment and to follow-up was complete as well their satisfaction. Conclusions: In centres skilled for laparoscopy in emergency, TAPP could be considered a feasible and safe technique. In well-selected patients (especially if emolled in controlled clinical trial) TAPP could represent an alternative surgical approach for complicated incarcerated inguinal hernia to conventional open surgery even in urgency. The main advantages of laparoscopic approach are the ability to perform surgical hernia reduction under vision, a better exploration and evaluation of abdominal cavity and diagnosis and treatment of eventual contralateral defect of wall, otherwise often missed. Finally, the good control of acute and chronic pain, faster return to normal activity and work, better aesthetic results contributed to total satisfaction and compliance of the patients

Human pluripotent embryonal carcinoma NTERA2 cl.D1 cells maintain their typical morphology in an angiomyogenic medium

BACKGROUND: Pluripotent embryonal carcinomas are good potential models, to study, "in vitro," the mechanisms that control differentiation during embryogenesis. The NTERA2cl.D1 (NT2/D1) cell line is a well known system of ectodermal differentiation. Retinoic acid (RA) induces a dorsal pattern of differentiation (essentially neurons) and bone morphogenetic protein (BMP) or hexamethylenebisacetamide (HMBA) induces a more ventral (epidermal) pattern of differentiation. However, whether these human cells could give rise to mesoderm derivatives as their counterpart in mouse remained elusive. We analyzed the morphological characteristics and transcriptional activation of genes pertinent in cardiac muscle and endothelium differentiation, during the growth of NT2/D1 cells in an inductive angiomyogenic medium with or without Bone Morphogenetic Protein 2 (BMP2). RESULTS: Our experiments showed that NT2/D1 maintains their typical actin organization in angiomyogenic medium. Although the beta myosin heavy chain gene was never detected, all the other 15 genes analyzed maintained their expression throughout the time course of the experiment. Among them were early and late cardiac, endothelial, neuronal and teratocarcinoma genes. CONCLUSION: Our results suggest that despite the NT2/D1 cells natural tendency to differentiate into neuroectodermal lineages, they can activate genes of mesodermal lineages. Therefore, we believe that these pluripotent cells might still be a good model to study biological development of mesodermal derivatives, provided the right culture conditions are met

Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs

<p>Abstract</p> <p>Background</p> <p>Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs) and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF) binding sites (TFBSs). Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed.</p> <p>Results</p> <p>We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was 21-75% more precise than a related CRM predictor. The sensitivity of the system to locate known human heart enhancers reached up to 83%. CrmMiner precision reached 82% while mining for CRMs specific to the human CD4⁺T cells. On several data sets, the system achieved 99% specificity.</p> <p>Conclusion</p> <p>These results suggest that CrmMiner predictions are accurate and likely to be tissue-specific CRMs. We expect that the predicted tissue-specific CRMs and the regulatory signatures broaden our knowledge of gene transcription regulation.</p

Sequence-selective detection of double-stranded DNA sequences using pyrrole-imidazole polyamide microarrays

We describe a microarray format that can detect double-stranded DNA sequences with a high degree of sequence selectivity. Cyclooctyne-derivatized pyrrole-imidazole polyamides were immobilized on azide-modified glass substrates using microcontact printing and a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. These polyamide-immobilized substrates selectively detected a seven-base-pair binding site incorporated within a double-stranded oligodeoxyribonucleotide sequence even in the presence of an excess of a sequence with a single-base-pair mismatc