Preventable cancer mortality in American Indian and Alaska Native women.

This report describes a series of six studies on cancer in American Indian and Alaska Native (AI/AN) women, with a particular emphasis on cancer of the breast and cervix. Data from the Indian Health Service (IHS) inpatient data system was used to generate estimates of incidence of cancer among AI/AN populations. Additionally, breast cancer rates among Indian women in Arizona and New Mexico were compiled from extensive chart review of the New Mexico Tumor Registry and the IHS Inpatient Data System. Study of the performance of the health care system for cancer screening in women suggest that the major deficiency lies not in a failure to bring women in for screening, but rather to complete the screening after contact has been made and the need for screening recognized. The studies indicate that cancer is generally diagnosed in American Indian women at a more advanced stage and survival experience of Indian cancer patients is worse than non-Indian, even when corrected for later stage at diagnosis. Several of the studies suggest that failure to diagnose cancer in its very early stages appears to be in large part dependent on patient behavior. An alarming number of women do not keep follow-up appointments, even after multiple referrals and rescheduling of appointments. These findings suggest the need for intervention strategies that encourage women to become knowledgeable about cancer and to accept responsibility for their screening. The studies suggest that the relative difficulty in improving screening rates are traced to an inadequate understanding of cancer and its prevention on the part of women in the community

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

Non-Committing Encryption with Constant Ciphertext Expansion from Standard Assumptions

Non-committing encryption (NCE) introduced by Canetti et al. (STOC \u2796) is a central tool to achieve multi-party computation protocols secure in the adaptive setting. Recently, Yoshida et al. (ASIACRYPT \u2719) proposed an NCE scheme based on the hardness of the DDH problem, which has ciphertext expansion $\mathcal{O}(\log\lambda)$ and public-key expansion $\mathcal{O}(\lambda^2)$. In this work, we improve their result and propose a methodology to construct an NCE scheme that achieves constant ciphertext expansion.Our methodology can be instantiated from the DDH assumption and the LWE assumption. When instantiated from the LWE assumption, the public-key expansion is $\lambda\cdot\mathsf{poly}(\log\lambda)$. They are the first NCE schemes satisfying constant ciphertext expansion without using iO or common reference strings. Along the way, we define a weak notion of NCE, which satisfies only weak forms of correctness and security.We show how to amplify such a weak NCE scheme into a full-fledged one using wiretap codes with a new security property

Sodium bicarbonate supplementation improves severe-intensity intermittent exercise under moderate acute hypoxic conditions

Acute moderate hypoxic exposure can substantially impair exercise performance, which occurs with a concurrent exacerbated rise in hydrogen cation (H+) production. The purpose of this study was therefore, to alleviate this acidic stress through sodium bicarbonate (NaHCO3) supplementation and determine the corresponding effects on severe intensity intermittent exercise performance. Eleven recreationally active individuals participated in this randomised, double-blind, crossover study performed under acute normobaric hypoxic conditions (FiO2% = 14.5%). Pre-experimental trials involved the determination of time to attain peak bicarbonate anion concentrations ([HCO3-]) following NaHCO3 ingestion. The intermittent exercise tests involved repeated 60 s work in their severe intensity domain and 30 s recovery at 20 W to exhaustion. Participants ingested either 0.3 g·kg bm-1 of NaHCO3 or a matched placebo of 0.21 g·kg bm-1 of sodium chloride prior to exercise. Exercise tolerance (+110.9 ± 100.6 s; 95% CI: 43.3 to 178 s; g = 1.0) and work performed in the severe intensity domain (+5.8 ± 6.6 kJ; 95% CI: 1.3 to 9.9 kJ; g = 0.8) were enhanced with NaHCO3 supplementation. Furthermore, a larger post-exercise blood lactate concentration was reported in the experimental group (+4 ± 2.4 mmol·l-1; 95% CI: 2.2 to 5.9; g = 1.8), while blood [HCO3-] and pH remained elevated in the NaHCO3 condition throughout experimentation. In conclusion, this study reported a positive effect of NaHCO3 under acute moderate hypoxic conditions during intermittent exercise and therefore, may offer an ergogenic strategy to mitigate hypoxic induced declines in exercise performance

The Circadian Clock Protein Timeless Regulates Phagocytosis of Bacteria in Drosophila

Survival of bacterial infection is the result of complex host-pathogen interactions. An often-overlooked aspect of these interactions is the circadian state of the host. Previously, we demonstrated that Drosophila mutants lacking the circadian regulatory proteins Timeless (Tim) and Period (Per) are sensitive to infection by S. pneumoniae. Sensitivity to infection can be mediated either by changes in resistance (control of microbial load) or tolerance (endurance of the pathogenic effects of infection). Here we show that Tim regulates resistance against both S. pneumoniae and S. marcescens. We set out to characterize and identify the underlying mechanism of resistance that is circadian-regulated. Using S. pneumoniae, we found that resistance oscillates daily in adult wild-type flies and that these oscillations are absent in Tim mutants. Drosophila have at least three main resistance mechanisms to kill high levels of bacteria in their hemolymph: melanization, antimicrobial peptides, and phagocytosis. We found that melanization is not circadian-regulated. We further found that basal levels of AMP gene expression exhibit time-of-day oscillations but that these are Tim-independent; moreover, infection-induced AMP gene expression is not circadian-regulated. We then show that phagocytosis is circadian-regulated. Wild-type flies exhibit up-regulated phagocytic activity at night; Tim mutants have normal phagocytic activity during the day but lack this night-time peak. Tim appears to regulate an upstream event in phagocytosis, such as bacterial recognition or activation of phagocytic hemocytes. Interestingly, inhibition of phagocytosis in wild type flies results in survival kinetics similar to Tim mutants after infection with S. pneumoniae. Taken together, these results suggest that loss of circadian oscillation of a specific immune function (phagocytosis) can have significant effects on long-term survival of infection

Disease and the Extended Phenotype: Parasites Control Host Performance and Survival through Induced Changes in Body Plan

BACKGROUND: By definition, parasites harm their hosts. However, some forms of parasite-induced alterations increase parasite transmission between hosts, such that manipulated hosts can be considered extensions of the parasite's phenotype. While well accepted in principle, surprisingly few studies have quantified how parasite manipulations alter host performance and survival under field and laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: By interfering with limb development, the trematode Ribeiroia ondatrae causes particularly severe morphological alterations within amphibian hosts that provide an ideal system to evaluate parasite-induced changes in phenotype. Here, we coupled laboratory performance trials with a capture-mark-recapture study of 1388 Pacific chorus frogs (Pseudacris regilla) to quantify the effects of parasite-induced malformations on host locomotion, foraging, and survival. Malformations, which affected ~50% of metamorphosing frogs in nature, caused dramatic reductions in all measures of organismal function. Malformed frogs exhibited significantly shorter jumping distances (41% reduction), slower swimming speeds (37% reduction), reduced endurance (66% reduction), and lower foraging success relative to infected hosts without malformations. Furthermore, while normal and malformed individuals had comparable survival within predator-free exclosures, deformed frogs in natural populations had 22% lower biweekly survival than normal frogs and rarely recruited to the adult population over a two-year period. CONCLUSIONS/SIGNIFICANCE: Our results highlight the ability of parasites to deeply alter multiple dimensions of host phenotype with important consequences for performance and survival. These patterns were best explained by malformation status, rather than infection per se, helping to decouple the direct and indirect effects of parasitism on host fitness.Brett A. Goodman and Pieter T. J. Johnso

From Mendel’s discovery on pea to today’s plant genetics and breeding

In 2015, we celebrated the 150th anniversary of the presentation of the seminal work of Gregor Johann Mendel. While Darwin’s theory of evolution was based on differential survival and differential reproductive success, Mendel’s theory of heredity relies on equality and stability throughout all stages of the life cycle. Darwin’s concepts were continuous variation and “soft” heredity; Mendel espoused discontinuous variation and “hard” heredity. Thus, the combination of Mendelian genetics with Darwin’s theory of natural selection was the process that resulted in the modern synthesis of evolutionary biology. Although biology, genetics, and genomics have been revolutionized in recent years, modern genetics will forever rely on simple principles founded on pea breeding using seven single gene characters. Purposeful use of mutants to study gene function is one of the essential tools of modern genetics. Today, over 100 plant species genomes have been sequenced. Mapping populations and their use in segregation of molecular markers and marker–trait association to map and isolate genes, were developed on the basis of Mendel's work. Genome-wide or genomic selection is a recent approach for the development of improved breeding lines. The analysis of complex traits has been enhanced by high-throughput phenotyping and developments in statistical and modeling methods for the analysis of phenotypic data. Introgression of novel alleles from landraces and wild relatives widens genetic diversity and improves traits; transgenic methodologies allow for the introduction of novel genes from diverse sources, and gene editing approaches offer possibilities to manipulate gene in a precise manner

Liquid biopsies come of age: towards implementation of circulating tumour DNA

Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a ‘liquid biopsy’ for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.We would like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A11906, A20240, A15601) (to N.R., J.D.B.), the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 337905 (to N.R.), the Cambridge Experimental Cancer Medicine Centre, and Hutchison Whampoa Limited (to N.R.), AstraZeneca (to R.B., S.P.), the Cambridge Experimental Cancer Medicine Centre (ECMC) (to R.B., S.P.), and NIHR Biomedical Research Centre (BRC) (to R.B., S.P.). J.G.C. acknowledges clinical fellowship support from SEOM