Does Immediate Breast Reconstruction after Mastectomy affect the Initiation of Adjuvant Chemotherapy?

Purpose: The frequency of immediate breast reconstruction (IBR) is increasing, and the types of reconstruction used are diverse. Adjuvant chemotherapy is a life-saving intervention in selected high-risk breast cancer patients. The aim of our study was to determine how IBR and type of reconstruction affect the timing of the initiation of chemotherapy. Methods: We obtained data from female breast cancer patients treated by mastectomy with IBR (IBR group) and without IBR (mastectomy only group) who received adjuvant chemotherapy between January 1, 2008, and December 31, 2010. We retrospectively collected data including patient characteristics, disease characteristics, treatment details, and treatment outcomes from our institutional electronic patient database and medical treatment records. The reconstruction types were categorized as deep inferior epigastric perforator (DIEP) flap, latissimus dorsi (LD) flap and tissue expander/implant (TEI). Results

Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases. Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease

Viral Perturbations of Host Networks Reflect Disease Etiology

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Tropical and subtropical Asia's valued tree species under threat

Tree diversity in Asia's tropical and subtropical forests is central to nature-based solutions. Species vulnerability to multiple threats, which affects the provision of ecosystem services, is poorly understood. We conducted a region-wide, spatially explicit vulnerability assessment (including overexploitation, fire, overgrazing, habitat conversion, and climate change) of 63 socio-economically important tree species selected from national priority lists and validated by an expert network representing 20 countries. Overall, 74% of the most important areas for conservation of these trees fall outside of protected areas, with species severely threatened across 47% of their native ranges. The most imminent threats are overexploitation and habitat conversion, with populations being severely threatened in an average of 24% and 16% of their distribution areas. Optimistically, our results predict relatively limited overall climate change impacts, however, some of the study species are likely to lose more than 15% of their habitat by 2050 because of climate change. We pinpoint specific natural forest areas in Malaysia and Indonesia (Borneo) as hotspots for on-site conservation of forest genetic resources, more than 82% of which do not currently fall within designated protected areas. We also identify degraded lands in Indonesia (Sumatra) as priorities for restoration where planting or assisted natural regeneration will help maintain these species into the future, while croplands in Southern India are highlighted as potentially important agroforestry options. Our study highlights the need for regionally coordinated action for effective conservation and restoration

Supplemental Material, COUPE_Competency_Framework.V6.submission - Does One Size Truly Fit All? The COUPE Undergraduate Perspective on Competency-Based Medical Education in Psychiatry

<p>Supplemental Material, COUPE_Competency_Framework.V6.submission for Does One Size Truly Fit All? The COUPE Undergraduate Perspective on Competency-Based Medical Education in Psychiatry by Natasja Menezes, Raed Hawa, Ron Oswald, and Elliott Kyung Lee in The Canadian Journal of Psychiatry</p