Skin-sparing mastectomy with immediate nipple reconstruction during autologous latissimus dorsi breast reconstruction: A review of patient satisfaction

Background Nipple-areolar complex (NAC) reconstruction following curative mastectomy is traditionally performed as a second-stage procedure several months after initial breast reconstruction. The recent literature has documented the increasing popularity of immediate nipple reconstruction carried out simultaneously during autologous reconstruction. The aim of this study was to evaluate the surgical outcomes and patient satisfaction with immediate breast and nipple reconstruction performed in a single stage after skin-sparing mastectomy. Methods All patients who underwent a skin-sparing mastectomy with immediate latissimus dorsi flap breast and NAC reconstruction as a single-stage procedure from 2007 to 2015 were included. Patient demographics, oncologic details, and surgical outcomes were recorded. The BREAST-Q questionnaire was administered to patients to assess the impact and effectiveness of this reconstructive strategy. Results During the study period, 34 breast and NAC reconstructions in 29 patients were performed at Cork University Hospital. The majority of our patient cohort were non-smokers (93.1%) and did not receive adjuvant radiotherapy. Postoperative complications were infrequent, with no cases of partial necrosis or complete loss of the nipple. The response rate to the BREAST-Q was 62% (n=18). Patients reported high levels of satisfaction with the reconstructed breast (62±4), nipple reconstruction (61±4.8), overall outcome (74.3±5), and psychosocialwell-being (77.7±3.2). Conclusions Skin-sparing mastectomy with immediate nipple reconstruction during autologous latissimus dorsi reconstruction was demonstrated to be a safe and aesthetically reliable procedure in our cohort, yielding high levels of psychological and physical well-being. A single-stage procedure promotes psychosocial well-being involving issues that are intrinsically linked with breast cancer surgery

TSS-1R Mission Failure Investigation Board

Reasons for the tether separation during the Tethered Satellite System (TSS-1) Mission are investigated. Lessons learned are presented

A Gene for Autosomal Recessive Limb-Girdle Muscular Dystrophy in Manitoba Hutterites Maps to Chromosome Region 9q31-q33: Evidence for Another Limb-Girdle Muscular Dystrophy Locus

SummaryCharacterized by proximal muscle weakness and wasting, limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of clinical disorders. Previous reports have documented either autosomal dominant or autosomal recessive modes of inheritance, with genetic linkage studies providing evidence for the existence of at least 12 distinct loci. Gene products have been identified for five genes responsible for autosomal recessive forms of the disorder. We performed a genome scan using pooled DNA from a large Hutterite kindred in which the affected members display a mild form of autosomal recessive LGMD. A total of 200 markers were used to screen pools of DNA from patients and their siblings. Linkage between the LGMD locus and D9S302 (maximum LOD score 5.99 at recombination fraction .03) was established. Since this marker resides within the chromosomal region known to harbor the gene causing Fukuyama congenital muscular dystrophy (FCMD), we expanded our investigations, to include additional markers in chromosome region 9q31-q34.1. Haplotype analysis revealed five recombinations that place the LGMD locus distal to the FCMD locus. The LGMD locus maps close to D9S934 (maximum multipoint LOD score 7.61) in a region that is estimated to be ∼4.4 Mb (Genetic Location Database composite map). On the basis of an inferred ancestral recombination, the gene may lie in a 300-kb region between D9S302 and D9S934. Our results provide compelling evidence that yet another gene is involved in LGMD; we suggest that it be named “LGMD2H.

Infrared Spectroscopy of Symbiotic Stars. IV. V2116 Ophiuchi/GX 1+4, The Neutron Star Symbiotic

We have computed, based on 17 infrared radial velocities, the first set of orbital elements for the M giant in the symbiotic binary V2116 Ophiuchi. The giant's companion is a neutron star, the bright X-ray source GX 1+4. We find an orbital period of 1161 days by far the longest of any known X-ray binary. The orbit has a modest eccentricity of 0.10 with an orbital circularization time of less than 10^6 years. The large mass function of the orbit significantly restricts the mass of the M giant. Adopting a neutron-star mass of 1.35M(Sun), the maximum mass of the M giant is 1.22M(Sun), making it the less massive star. Derived abundances indicate a slightly subsolar metallicity. Carbon and nitrogen are in the expected ratio resulting from the red-giant first dredge-up phase. The lack of O-17 suggests that the M-giant has a mass less than 1.3M(Sun), consistent with our maximum mass. The red giant radius is 103R(Sun), much smaller than the estimated Roche lobe radius. Thus, the mass loss of the red giant is via a stellar wind. Although the M giant companion to the neutron star has a mass similar to the late-type star in low-mass X-ray binaries, its near-solar abundances and apparent runaway velocity are not fully consistent with the properties of this class of stars.Comment: In press to The Astrophysical Journal (10 April 2006 issue). 23 page

Observations of storm-induced mixing and Gulf Stream Ring incursion over the southern flank of Georges Bank : winter and summer 1997

Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 115 (2010): C08008, doi:10.1029/2009JC005706.High-resolution hydrographic measurements collected along the southern edge of Georges Bank during March and June–July 1997 focused on characterizing processes that drive fluxes of material between the slope and bank. Wintertime sampling characterized changes driven by a strong storm. A Scotian Shelf crossover event produced a ribbon of anomalously fresh water along the bank's southern flank that was diluted during the storm. Comparison of prestorm and poststorm sections shows that over the bank changes in heat and salt inventories are consistent with those expected solely from local surface fluxes. In deeper waters, advective effects, likely associated with frontal motion and eddies, are clearly important. Summertime surveys resolve the development of a massive intrusion of Gulf Stream-like waters onto the bank. East of the intrusion, a thin extrusion of bank water is drawn outward by the developing ring, exporting fresher water at a rate of about 7 × 104 m3/s. A large-amplitude Gulf Stream meander appears to initiate the extrusion, but it quickly evolves, near the bank edge, into a warm core ring. Ring water intrudes to approximately the 80 m isobath, 40 km inshore from the bank edge. The intrusion process seems analogous to the development of Gulf Stream shingles (a hydrodynamic instability) in the South Atlantic Bight. It appears that, once the intruded water is established on the bank, it remains there and dissipates in place. Although the intrusion is an extremely dramatic event, it is probably not actually a major contributor to shelf edge exchanges over a seasonal time scale.This work was supported by the National Science Foundation as part of the U.S. Global Ocean Ecosystems Dynamics (GLOBEC) program through grant OCE-9632349. Lee received additional support from OCE-0628379

Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer.

In the United States, pancreatic cancer is a major cause of cancer-related deaths. Although substantial efforts have been made to understand pancreatic cancer biology and improve therapeutic efficacy, patients still face a bleak chance of survival. A greater understanding of pancreatic cancer development and the identification of novel treatment targets are desperately needed. Our analysis of gene expression data from patient samples showed an increase in amyloid precursor-like protein 2 (APLP2) expression within primary tumor epithelium relative to pancreatic intraepithelial neoplasia (PanIN) epithelial cells. Augmented expression of APLP2 in primary tumors compared to adjacent stroma was also observed. Genetically engineered mouse models of spontaneous pancreatic ductal adenocarcinoma were used to investigate APLP2\u27s role in cancer development. We found that APLP2 expression intensifies significantly during pancreatic cancer initiation and progression in the LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mouse model, as shown by immunohistochemistry analysis. In studies utilizing pancreas-specific heterozygous and homozygous knockout of APLP2 in the KPC mouse model background, we observed significantly prolonged survival and reduced metastatic progression of pancreatic cancer. These results demonstrate the importance of APLP2 in pancreatic cancer initiation and metastasis and indicate that APLP2 should be considered a potential therapeutic target for this disease

Constraining the Twomey effect from satellite observations: issues and perspectives

The Twomey effect describes the radiative forcing associated with a change in cloud albedo due to an increase in anthropogenic aerosol emissions. It is driven by the perturbation in cloud droplet number concentration (1Nd; ant) in liquid-water clouds and is currently understood to exert a cooling effect on climate. The Twomey effect is the key driver in the effective radiative forcing due to aerosol–cloud interactions, but rapid adjustments also contribute. These adjustments are essentially the responses of cloud fraction and liquid water path to 1Nd; ant and thus scale approximately with it. While the fundamental physics of the influence of added aerosol particles on the droplet concentration (Nd) is well described by established theory at the particle scale (micrometres), how this relationship is expressed at the large-scale (hundreds of kilometres) perturbation, 1Nd; ant, remains uncertain. The discrepancy between process understanding at particle scale and insufficient quantification at the climate-relevant large scale is caused by co-variability of aerosol particles and updraught velocity and by droplet sink processes. These operate at scales on the order of tens of metres at which only localised observations are available and at which no approach yet exists to quantify the anthropogenic perturbation. Different atmospheric models suggest diverse magnitudes of the Twomey effect even when applying the same anthropogenic aerosol emission perturbation. Thus, observational data are needed to quantify and constrain the Twomey effect. At the global scale, this means satellite data. There are four key uncertainties in determining 1Nd; ant, namely the quantification of (i) the cloud-active aerosol – the cloud condensation nuclei (CCN) concentrations at or above cloud base, (ii) Nd, (iii) the statistical approach for inferring the sensitivity of Nd to aerosol particles from the satellite data and (iv) uncertainty in the anthropogenic perturbation to CCN concentrations, which is not easily accessible from observational data. This review discusses deficiencies of current approaches for the different aspects of the problem and proposes several ways forward: in terms of CCN, retrievals of optical quantities such as aerosol optical depth suffer from a lack of vertical resolution, size and hygroscopicity information, non-direct relation to the concentration of aerosols, difficulty to quantify it within or below clouds, and the problem of insufficient sensitivity at low concentrations, in addition to retrieval errors. A future path forward can include utilising co-located polarimeter and lidar instruments, ideally including high-spectral-resolution lidar capability at two wavelengths to maximise vertically resolved size distribution information content. In terms of Nd, a key problem is the lack of operational retrievals of this quantity and the inaccuracy of the retrieval especially in broken-cloud regimes. As for the Nd-to-CCN sensitivity, key issues are the updraught distributions and the role of Nd sink processes, for which empirical assessments for specific cloud regimes are currently the best solutions. These considerations point to the conclusion that past studies using existing approaches have likely underestimated the true sensitivity and, thus, the radiative forcing due to the Twomey effect

EvoChromo: towards a synthesis of chromatin biology and evolution

Over the past few years, interest in chromatin and its evolution has grown. To further advance these interests, we organized a workshop with the support of The Company of Biologists to debate the current state of knowledge regarding the origin and evolution of chromatin. This workshop led to prospective views on the development of a new field of research that we term ‘EvoChromo’. In this short Spotlight article, we define the breadth and expected impact of this new area of scientific inquiry on our understanding of both chromatin and evolution

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies