Forgotten Borrowers: Protecting Private Student Loan Borrowers Through State Law

Private student loan borrowers arguably have the fewest protections of any users of credit in the United States. In a scarcely debated amendment to federal bankruptcy law in 2005, private student lenders gained the same protections against discharge previously afforded to federal student lenders. Yet private student loan borrowers received none of the rights available to federal student loan borrowers. These include income-driven repayment, relief from repayment on disability, loan discharge for fraud or closed schools, and public service loan forgiveness. Private student loan borrowers thus have neither the bankruptcy protections afforded to nonstudent loan debtors nor the repayment and debt relief rights of student borrowers under the federal loan program. This lack of consumer protection has particular consequence when considering the plight of for-profit school students saddled with private student loans. Some of the worst abuses in the proliferation of higher education debt have been perpetrated against for-profit school attendees. The vast majority of private student loans are cosigned, typically by older family members. This combination of private student loans and for-profit school attendance impacts a much broader range of consumers than would a comparable number of federal student loans. We suggest two types of state legislation to protect these debtors. For prospective for-profit school private borrowers, we propose incorporating some of the protections of federal student loans through the use of a state equivalent to the Federal Trade Commission “Holder Rule.” For all private student loans, we propose a requirement that private lenders engage in a mandatory settlement process, similar to those used by states during the recent foreclosure crisis, as a prerequisite to using state courts for debt collection

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Forgotten Borrowers: Protecting Private Student Loan Borrowers Through State Law

Private student loan borrowers arguably have the fewest protections of any users of credit in the United States. In a scarcely debated amendment to federal bankruptcy law in 2005, private student lenders gained the same protections against discharge previously afforded to federal student lenders. Yet private student loan borrowers received none of the rights available to federal student loan borrowers. These include income-driven repayment, relief from repayment on disability, loan discharge for fraud or closed schools, and public service loan forgiveness. Private student loan borrowers thus have neither the bankruptcy protections afforded to nonstudent loan debtors nor the repayment and debt relief rights of student borrowers under the federal loan program. This lack of consumer protection has particular consequence when considering the plight of for-profit school students saddled with private student loans. Some of the worst abuses in the proliferation of higher education debt have been perpetrated against for-profit school attendees. The vast majority of private student loans are cosigned, typically by older family members. This combination of private student loans and for-profit school attendance impacts a much broader range of consumers than would a comparable number of federal student loans. We suggest two types of state legislation to protect these debtors. For prospective for-profit school private borrowers, we propose incorporating some of the protections of federal student loans through the use of a state equivalent to the Federal Trade Commission “Holder Rule.” For all private student loans, we propose a requirement that private lenders engage in a mandatory settlement process, similar to those used by states during the recent foreclosure crisis, as a prerequisite to using state courts for debt collection

Efficacy of Proton Beam Therapy in the Treatment of Ewing's Sarcoma of the Paranasal Sinuses and Anterior Skull Base

Ewing's sarcoma involving the sinonasal cavity and anterior skull base is very rare. The purpose of this article is to present our experience with two such cases, which were both treated with combined chemotherapy and proton beam radiation therapy. The patients were selected from a retrospective medical record analysis that was conducted of all patients who were diagnosed with Ewing's sarcoma of the sinonasal cavity at the Massachusetts Eye & Ear Infirmary/Massachusetts General Hospital Cranial Base Center from 2004 to 2008. One of the patients underwent pretreatment endoscopic subtotal resection to facilitate proton beam radiation therapy. Response to treatment was assessed, post-treatment endoscopic biopsies were performed to assure eradication of disease, and treatment complications were recorded. Both patients completed chemotherapy and proton beam radiation therapy without complication. One patient completed treatment in December 2006 and remains disease free. The second patient completed treatment in March 2007 and remains disease free. Both patients developed headaches accompanied by frontal sinus opacification after treatment that required endoscopic drainage. After endoscopic drainage, the opacification and symptoms resolved

Immediate and Delayed Complications Following Endoscopic Skull Base Surgery

Objectives To characterize the temporal distribution and resolution rate of postoperative complications from endoscopic skull base surgery. Design Retrospective review of patients undergoing endoscopic resection of paranasal sinus or skull base neoplasm from 2007 to 2013. Setting Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary Cranial Base Center. Participants Fifty-eight consecutive patients. Main Outcome Measures Postoperative complications were categorized as cerebrospinal fluid (CSF) leak, pituitary, orbital, intracranial, or sinonasal. Complications were temporally categorized as “perioperative” (within 1 week), “early” (after 1 week and within 6 months), or “delayed” (after 6 months). Results The most common perioperative complications were diabetes insipidus (19.0%), CSF leak (5.2%), and meningitis (5.2%), with resolution rates of 75%, 100%, and 100%, respectively. Overall, CSF leak occurred in 13.8% of patients and resolved in all cases. A total of 53.8% of all complications were evident within 1 week of surgery. Chronic rhinosinusitis was the most common delayed complication (3.4%). Hypopituitarism and delayed complications were less likely to resolve (p = 0.014 and p = 0.080, respectively). Conclusions Monitoring of complications after endoscopic skull base surgery should focus on neurologic complications and CSF leak in the early postoperative period and development of chronic rhinosinusitis in the long term. Late-onset complications and hypopituitarism are less likely to resolve

Resistance to therapy caused by intragenic deletion in BRCA2

Cells with loss of BRCA2 function are defective in homologous recombination ( HR) and are highly sensitive to inhibitors of poly( ADP- ribose) polymerase ( PARP)(1,2), which provides the basis for a new therapeutic approach. Here we show that resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. We derived PARP- inhibitor- resistant ( PIR) clones from the human CAPAN1 pancreatic cancer cell line, which carries the protein- truncating c.6174delT frameshift mutation. PIR clones could form DNA- damage- induced RAD51 nuclear foci and were able to limit genotoxin- induced genomic instability, both hallmarks of a competent HR pathway. New BRCA2 isoforms were expressed in the resistant lines as a result of intragenic deletion of the c.6174delT mutation and restoration of the open reading frame ( ORF). Reconstitution of BRCA2- deficient cells with these revertant BRCA2 alleles rescued PARP inhibitor sensitivity and HR deficiency. Most of the deletions in BRCA2 were associated with small tracts of homology, and possibly arose from error-prone repair caused by BRCA2 deficiency(3,4). Similar ORF-restoring mutations were present in carboplatin- resistant ovarian tumours from c.6174delT mutation carriers. These observations have implications for understanding drug resistance in BRCA mutation carriers as well as in defining functionally important domains within BRCA2

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts