An improved method of in vivo wound disruption and measurement

Biomechanical studies of wound strength are important because of new investigations in growth factors, cytokines, and fetal wounds. We compared two traditional methods of wound disruption measurement with a novel computerized model designed for in vivo experiments. An Instron tensiometer (INSTS) and an air insufflated positive pressure device (AIPPD) were compared with a vacuum-controlled wound chamber device (VCWCD). The VCWCD produced vacuum at the wound site and wound disruption was monitored with two video camera/recorders. Rats were marked with a template guide for a 2.5 cm, full-thickness, abdominal incisional wound. Rats were divided into three groups and studied at 2, 7, or 14 days after wounding. The recorded images were computer digitalized to generate wound strength curves from a three-dimensional model. A comparison of the wound disruption curves demonstrated that the VCWCD was comparable to the INST or AIPPD in normal wound healing (P> .40). The VCWCD provided data with less standard error at 2 days after wounding (P P in vivo method which required minimal wound manipulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30176/1/0000561.pd

Double Diffraction Dissociation at the Fermilab Tevatron Collider

We present results from a measurement of double diffraction dissociation in $\bar pp$ collisions at the Fermilab Tevatron collider. The production cross section for events with a central pseudorapidity gap of width $\Delta\eta^0>3$ (overlapping $\eta=0$) is found to be $4.43\pm 0.02{(stat)}{\pm 1.18}{(syst) mb}$ [$3.42\pm 0.01{(stat)}{\pm 1.09}{(syst) mb}$] at $\sqrt{s}=1800$ [630] GeV. Our results are compared with previous measurements and with predictions based on Regge theory and factorization.Comment: 10 pages, 4 figures, using RevTeX. Submitted to Physical Review Letter

Measurement of the Top Quark Mass with the Collider Detector at Fermilab

This report describes a measurement of the top quark mass in \ppbar collisions at a center of mass energy of 1.8 TeV. The data sample was collected with the CDF detector during the 1992--95 collider run at the Fermilab Tevatron, and corresponds to an integrated luminosity of 106 \pb. Candidate $t\bar{t}$ events in the ``lepton+jets'' decay channel provide our most precise measurement of the top quark mass. For each event a top mass is determined by using energy and momentum constraints on the production of the \ttbar pair and its subsequent decay. A likelihood fit to the distribution of reconstructed masses in the data sample gives a top mass in the lepton+jets channel of 176.1\pm 5.1 (stat.)\pm 5.3 (syst.) \gevcc. Combining this result with measurements from the ``all-hadronic'' and ``dilepton'' decay topologies yields a top mass of 176.1\pm 6.6 \gevcc.Comment: 158 pages, 41 figure

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM (-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Observation of Higgs boson production in association with a top quark pair at the LHC with the ATLAS detector

The observation of Higgs boson production in association with a top quark pair (tt H¯ ), based on the analysis of proton–proton collision data at a centre-of-mass energy of 13 TeV recorded with the ATLAS detector at the Large Hadron Collider, is presented. Using data corresponding to integrated luminosities of up to 79.8 fb−1, and considering Higgs boson decays into b¯ b, W W ∗, τ +τ −, γγ , and Z Z∗, the observed significance is 5.8 standard deviations, compared to an expectation of 4.9 standard deviations. Combined with the tt H¯ searches using a dataset corresponding to integrated luminosities of 4.5 fb−1 at 7 TeV and 20.3 fb−1 at 8 TeV, the observed (expected) significance is 6.3 (5.1) standard deviations. Assuming Standard Model branching fractions, the total tt H¯ production cross section at 13 TeV is measured to be 670 ± 90 (stat.) +110 −100 (syst.) fb, in agreement with the Standard Model prediction

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Caregiver satisfaction survey results in a multidisciplinary cleft clinic

**Introduction**: Orofacial clefts have a wide range of severity and can create functional and aesthetic issues for the affected individuals as well as influence their social interactions and general happiness. The aim of this research was to investigate how parents/caregivers score functional and aesthetic aspects of their child’s cleft and their child’s social interactions and happiness. **Method**: Parents/caregivers attending the Christchurch Cleft Clinic in New Zealand between 2016 and 2019 were asked to complete a survey covering eight items—hearing, look of face, look of teeth, speech, teeth issues, food or liquid coming out of the nose, social interactions, general happiness and a free-text comment section. Items were scored using a visual analogue scale. Descriptive statistics were performed on the data and qualitative analysis of the free-text comments was conducted via thematic categorisation. The study was deemed an out-of-scope audit from the New Zealand Health and Disability Ethics Committee; locality approval was granted by the Canterbury District Health Board (RO# 19069) and consent was obtained from all participants. **Results**: A total of 226 completed surveys from 154 parents were assessed. Surveys that had any incomplete question (24) and/or had repeat submissions (72) were excluded, reducing the sample to 130 surveys. ‘Speech’, ‘look of the teeth’ and ‘teeth issues’ had the lowest (worst) mean scores. Negative functional issues relating to speech and fistulas were the most common free-text themes. **Conclusion**: Speech was a common concern for parents, emphasising the importance of speech language therapy as a key component in cleft treatment. Parental concerns regarding the look of their child’s teeth and teeth issues highlight the need for an interdisciplinary treatment approach. The inclusion of otolaryngology and psychology services to improve issues that arise from hearing, social and emotional challenges is also recommended

BMPR2 Haploinsufficiency as the Inherited Molecular Mechanism for Primary Pulmonary Hypertension

Primary pulmonary hypertension (PPH) is a potentially lethal disorder, because the elevation of the pulmonary arterial pressure may result in right-heart failure. Histologically, the disorder is characterized by proliferation of pulmonary-artery smooth muscle and endothelial cells, by intimal hyperplasia, and by in situ thrombus formation. Heterozygous mutations within the bone morphogenetic protein type II receptor (BMPR-II) gene (BMPR2), of the transforming growth factor β (TGF-β) cell–signaling superfamily, have been identified in familial and sporadic cases of PPH. We report the molecular spectrum of BMPR2 mutations in 47 additional families with PPH and in three patients with sporadic PPH. Among the cohort of patients, we have identified 22 novel mutations, including 4 partial deletions, distributed throughout the BMPR2 gene. The majority (58%) of mutations are predicted to lead to a premature termination codon. We have also investigated the functional impact and genotype-phenotype relationships, to elucidate the mechanisms contributing to pathogenesis of this important vascular disease. In vitro expression analysis demonstrated loss of BMPR-II function for a number of the identified mutations. These data support the suggestion that haploinsufficiency represents the common molecular mechanism in PPH. Marked variability of the age at onset of disease was observed both within and between families. Taken together, these studies illustrate the considerable heterogeneity of BMPR2 mutations that cause PPH, and they strongly suggest that additional factors, genetic and/or environmental, may be required for the development of the clinical phenotype