Financial Impact of Complex Cancer Surgery in India: A Study of Pancreatic Cancer.

PURPOSE: The rapidly increasing burden of cancer in India has profound impacts on health care costs for patients and their families. High out-of-pocket (OOP) expenditure, lack of insurance, and low government expenditure create a vicious cycle, leading to household impoverishment. Complex cancer surgery is now increasingly important for emerging countries; however, little is understood about the macro- and microeconomics of these procedures. After the Lancet Oncology Commission on Global Cancer Surgery, we evaluated the OOP expenditure for patients undergoing pancreatico-duodenectomy (PD) at a government tertiary cancer center in India. METHODS: Prospective data from 98 patients who underwent PD between January 2014 and June 2015 were collected and analyzed. The time frame for consideration of expenses, including all preoperative investigations, was from the first hospital visit to the day of discharge. Catastrophic expenditure was calculated by assessing the percentage of households in which OOP health payments exceeded 10% of the total household income. RESULTS: The mean expenditure for PD by patients was Rs.295,679.57 (US$74,420, purchasing power parity corrected). This amount was significantly higher among those admitted to a private ward and those with complications. Only 29.6% of the patients had insurance coverage. A total of 76.5% of the sample incurred catastrophic expenditure, and 38% of those with insurance underwent financial catastrophe compared with 93% of those without insurance. The percentage of patients facing catastrophic impact was highest among those in semiprivate wards, at 86.7%, followed by those in public and private wards. CONCLUSION: The cost of PD is high and is often unaffordable for a majority of India's population. A review of insurance coverage policies for better coverage must be considered

Eisenhart, Margaret, and Lisa Towne, Contestation and Change in National Policy on \u27Scientifically Bases\u27 Education Research, Educational Researcher, 32(October, 2003), 31-38.

Traces the definitions of educational research that appear in varied federal education legislation passed in 2000 through 2003 and notes the uses intended for each and the effect of outside testimony in shifting the language that eventually appeared in these laws

High-Resolution Epitope Mapping and Affinity Binding Analysis Comparing a New Anti-Human LAG3 Rabbit Antibody Clone to the Commonly Used Mouse 17B4 Clone

Lymphocyte activation gene 3 (LAG3) is a T cell inhibitory receptor that promotes tumor cell immune escape and is a potential target for cancer diagnostic and immunotherapeutic applications. We used automated capillary electrophoresis (ACE), surface plasmon resonance (SPR), and immunohistochemistry (IHC) to compare the binding characteristics of a new anti-LAG3 rabbit antibody clone, SP464, with the thirty-year old and extensively used anti-LAG3 mouse 17B4 clone. The rabbit SP464 clone exhibited between 20× to 30× greater binding to LAG3 than did the mouse 17B4 clone. Using these tools, we precisely mapped the relative locations of the epitopes of these two antibodies. The SP464 and 17B4 minimal epitopes were localized to separate, but overlapping, sub-fragments within the amino-terminal fifteen acids of the original thirty-mer peptide immunogen used to generate both antibodies. Application of this approach for quantifying the effects of alanine substitutions along the minimal SP464 epitope identified two amino acids essential for binding and four amino acids that likely contribute towards binding. Together, ACE, SPR, and IHC constitute a powerful orthologous approach for comparing antibody-binding characteristics and for fine mapping of linear epitopes within short immunogens. Our results indicate that the rabbit clone SP464 may be useful for assessing LAG3 expression

Puromycin-sensitive aminopeptidase limits MHC class I presentation in dendritic cells but does not affect CD8 T cell responses during viral infections

Previous experiments using enzyme inhibitors, cell lysates, and purified enzyme have suggested that puromycin-sensitive aminopeptidase (PSA) plays a role in creating and destroying MHC class I-presented peptides although its precise contribution to these processes is unknown. To examine the importance of this enzyme in MHC class I Ag presentation, we have generated PSA-deficient mice and cell lines from these animals. PSA-deficient mice are smaller and do not reproduce as well as wild type mice. In addition, dendritic cells from PSA-deficient mice display more MHC class I molecules on the cell surface, suggesting that PSA normally limits Ag presentation by destroying certain peptides in these key APCs. Surprisingly, MHC class I levels are not altered on other PSA-deficient cells and the processing and presentation of peptide precursors in PSA-deficient fibroblasts is normal. Moreover, PSA-deficient mice have normal numbers of T cells in the periphery, and respond as well as wild type mice to eight epitopes from three viruses. These data indicate that PSA may play a role in limiting MHC class I Ag presentation in dendritic cells in vivo but that it is not essential for generating most MHC class I-presented peptides or for stimulating CTL responses to several Ags

Leucine aminopeptidase is not essential for trimming peptides in the cytosol or generating epitopes for MHC class I antigen presentation

To detect viral infections and tumors, CD8+ T lymphocytes monitor cells for the presence of antigenic peptides bound to MHC class I molecules. The majority of MHC class I-presented peptides are generated from the cleavage of cellular and viral proteins by the ubiquitin-proteasome pathway. Many of the oligopeptides produced by this process are too long to stably bind to MHC class I molecules and require further trimming for presentation. Leucine aminopeptidase (LAP) is an IFN-inducible cytosolic aminopeptidase that can trim precursor peptides to mature epitopes and has been thought to play an important role in Ag presentation. To examine the role of LAP in generating MHC class I peptides in vivo, we generated LAP-deficient mice and LAP-deficient cell lines. These mutant mice and cells are viable and grow normally. The trimming of peptides in LAP-deficient cells is not reduced under basal conditions or after stimulation with IFN. Similarly, there is no reduction in presentation of peptides from precursor or full-length Ag constructs or in the overall supply of peptides from cellular proteins to MHC class I molecules even after stimulation with IFN. After viral infection, LAP-deficient mice generate normal CTL responses to seven epitopes from three different viruses. These data demonstrate that LAP is not an essential enzyme for generating most MHC class I-presented peptides and reveal redundancy in the function of cellular aminopeptidases

When moments matter: Finding answers with rapid exome sequencing

Abstract Background When time is of the essence in critical care cases, a fast molecular diagnosis is often necessary to help health care providers quickly determine best next steps for treatments, prognosis, and counseling of their patients. In this paper, we present the diagnostic rates and improved quality of life for patients undergoing clinical rapid exome sequencing. Methods The clinical histories and results of 41 patients undergoing rapid exome sequencing were retrospectively reviewed. Results Clinical rapid exome sequencing identified a definitive diagnosis in 13/41 (31.7%) and other relevant findings in 17 of the patients (41.5%). The average time to verbal report was 7 days; to written report was 11 days. Conclusions Our observations demonstrate the utility and effectiveness of rapid family‐based diagnostic exome sequencing in improving patients care

The Role of Scavenging in Disease Dynamics

Contents Introduction................ 161 The Use of Animal Remains and the Exposure of Scavengers to Disease........ 163 The Relevance of Scavenging for Pathogens to Spread and Persist.......... 166 Human Related Factors Resulting in Increased Risk for Disease Transmission Through Scavenging.............. 170 Management of Scavenging to Reduce Disease Risks.............. 173 Restoration of Large Predators.................. 174 Elimination of Hunting of Scavengers............ 174 Destruction of Big Game and Domestic Animal Carcasses........... 174 Restoration of the Effects of Overabundance............. 175 Excluding Mammalian and Avian Scavengers from Natural Carrions.......... 176 Excluding Mammalian and Avian Scavengers from Vulture Restaurants........... 176 Conclusions and Future Perspectives........... 178 References............... 17

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions