Impact of screening on cervical cancer incidence: A population-based case-control study in the United States.

Cervical cancer is widely preventable through screening, but little is known about the duration of protection offered by a negative screen in North America. A case-control study was conducted with records from population-based registries in New Mexico. Cases were women diagnosed with cervical cancer in 2006-2016, obtained from the Tumor Registry. Five controls per case from the New Mexico HPV Pap Registry were matched to cases by sex, age and place of residence. Dates and results of all cervical screening and diagnostic tests since 2006 were identified from the pap registry. We estimated the odds ratio of nonlocalized (Stage II+) and localized (Stage I) cervical cancer associated with attending screening in the 3 years prior to case-diagnosis compared to women not screened in 5 years. Of 876 cases, 527 were aged 25-64 years with ≥3 years of potential screening data. Only 38% of cases and 61% of controls attended screening in a 3-year period. Women screened in the 3 years prior to diagnosis had 83% lower risk of nonlocalized cancer (odds ratio [OR] = 0.17, 95% CI: 0.12-0.24) and 48% lower odds of localized cancer (OR = 0.52, 95% CI: 0.38-0.72), compared to women not screened in the 5 years prior to diagnosis. Women remained at low risk of nonlocalized cancer for 3.5-5 years after a negative screen compared to women with no negative screens in the 5 years prior to diagnosis. Routine cervical screening is effective at preventing localized and nonlocalized cervical cancers; 3 yearly screening prevents 83% of nonlocalized cancers, with no additional benefit of more frequent screening. Increasing screening coverage remains essential to further reduce cervical cancer incidence.This work was supported by the US National Cancer Institute (NCI) U54CA164336 to CMW (CMW, CLW, MR) with subcontracts to Texas A & M University, College Station, Texas (YJM, DWG) and to University of Alabama at Birmingham (ICS) and by the US National Institute of Allergy and Infectious Diseases U19AI113187 to CMW with subcontract to Queen Mary University of London (QMUL) (JC, PDS). This project was also supported by Contract HHSN261201800014I, Task Order HHSN26100001 from the National Cancer Institute (CLW). In addition, support was received from Cancer Research UK programme grants C8161/A1689 to PDS (RL, CM) and C569/A16891 to JC, from NCI P30CA118100 (to CL Willman) (YJM) and the Ford Foundation (YJM)

State-of-the-art three-dimensional analysis of soft tissue changes following Le Fort I maxillary advancement

We describe the comprehensive 3-dimensional analysis of facial changes after Le Fort I osteotomy and introduce a new tool for anthropometric analysis of the face. We studied the cone-beam computed tomograms of 33 patients taken one month before and 6-12 months after Le Fort I maxillary advancement with or without posterior vertical impaction. Use of a generic facial mesh for dense correspondence analysis of changes in the soft tissue showed a mean (SD) anteroposterior advancement of the maxilla of 5.9 (1.7) mm, and mean (SD) minimal anterior and posterior vertical maxillary impaction of 0.1 (1.7) mm and 0.6 (1.45) mm, respectively. It also showed distinctive forward and marked lateral expansion around the upper lip and nose, and pronounced upward movement of the alar curvature and columella. The nose was widened and the nostrils advanced. There was minimal forward change at the base of the nose (subnasale and alar base) but a noticeable upward movement at the nasal tip. Changes at the cheeks were minimal. Analysis showed widening of the midface and upper lip which, to our knowledge, has not been reported before. The nostrils were compressed and widened, and the lower lip shortened. Changes at the chin and lower lip were secondary to the limited maxillary impaction

Drug resistance in cancer

Cancer Research UK has recently sponsored a meeting, organized by the UK Medical Research Council, on cancer drug resistance. Several of the molecular mechanisms responsible for this clinical outcome, such as DNA interstrand crosslink repair, apoptosis evasion, cytochrome P450 and P-glycoprotein, were discussed. There was a special focus on leukaemia, breast and ovarian cancer, and the potential use of positron-emission tomography to study anticancer-drug resistance. The progress made in translating these findings to the clinic, like Gefitinib, P-glycoprotein phenotyping, or genome-wide analysis technology, was also discussed

Anatomy of quantum chaotic eigenstates

The eigenfunctions of quantized chaotic systems cannot be described by explicit formulas, even approximate ones. This survey summarizes (selected) analytical approaches used to describe these eigenstates, in the semiclassical limit. The levels of description are macroscopic (one wants to understand the quantum averages of smooth observables), and microscopic (one wants informations on maxima of eigenfunctions, "scars" of periodic orbits, structure of the nodal sets and domains, local correlations), and often focusses on statistical results. Various models of "random wavefunctions" have been introduced to understand these statistical properties, with usually good agreement with the numerical data. We also discuss some specific systems (like arithmetic ones) which depart from these random models.Comment: Corrected typos, added a few references and updated some result

Sex-specific regulation of chemokine Cxcl5/6 controls neutrophil recruitment and tissue injury in acute inflammatory states

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Barts and The London Trustees Studentship (SM), Marie Curie fellowships (MB, JD), Arthritis Research UK career development fellowship (JW), William Harvey Research Foundation grant (JW/RSS), Kidney Research UK fellowship (NSAP), Barts and The London Vacation Scholarship (ISN), Wellcome Trust senior fellowship (DWG), and a Wellcome Trust career development fellowship (RSS). This work forms part of the research themes contributing to the translational research portfolio of Barts and The London Cardiovascular Biomedical Research Unit, which is supported and funded by National Institute for Health Researc

The Abundance of Pink-Pigmented Facultative Methylotrophs in the Root Zone of Plant Species in Invaded Coastal Sage Scrub Habitat

Pink-pigmented facultative methylotrophic bacteria (PPFMs) are associated with the roots, leaves and seeds of most terrestrial plants and utilize volatile C1 compounds such as methanol generated by growing plants during cell division. PPFMs have been well studied in agricultural systems due to their importance in crop seed germination, yield, pathogen resistance and drought stress tolerance. In contrast, little is known about the PPFM abundance and diversity in natural ecosystems, let alone their interactions with non-crop species. Here we surveyed PPFM abundance in the root zone soil of 5 native and 5 invasive plant species along ten invasion gradients in Southern California coastal sage scrub habitat. PPFMs were present in every soil sample and ranged in abundance from 102 to 105 CFU/g dry soil. This abundance varied significantly among plant species. PPFM abundance was 50% higher in the root zones of annual or biennial species (many invasives) than perennial species (all natives). Further, PPFM abundance appears to be influenced by the plant community beyond the root zone; pure stands of either native or invasive species had 50% more PPFMs than mixed species stands. In sum, PPFM abundance in the root zone of coastal sage scrub plants is influenced by both the immediate and surrounding plant communities. The results also suggest that PPFMs are a good target for future work on plant-microorganism feedbacks in natural ecosystems

Key issues in the design of pay for performance programs

Pay for performance (P4P) is increasingly being used to stimulate healthcare providers to improve their performance. However, evidence on P4P effectiveness remains inconclusive. Flaws in program design may have contributed to this limited success. Based on a synthesis of relevant theoretical and empirical literature, this paper discusses key issues in P4P-program design. The analysis reveals that designing a fair and effective program is a complex undertaking. The following tentative conclusions are made: (1) performance is ideally defined broadly, provided that the set of measures remains comprehensible, (2) concerns that P4P encourages "selection" and "teaching to the test" should not be dismissed, (3) sophisticated risk adjustment is important, especially in outcome and resource use measures, (4) involving providers in program design is vital, (5) on balance, group incentives are preferred over individual incentives, (6) whether to use rewards or penalties is context-dependent, (7) payouts should be frequent and low-powered, (8) absolute targets are generally preferred over relative targets, (9) multiple targets are preferred over single targets, and (10) P4P should be a permanent component of provider compensation and is ideally "decoupled" form base payments. However, the design of P4P programs should be tailored to the specific setting of implementation, and empirical research is needed to confirm the conclusions

Effects of adenosine A2A receptor activation and alanyl-glutamine in Clostridium difficile toxin-induced ileitis in rabbits and cecitis in mice

<p>Abstract</p> <p>Background</p> <p>Severe <it>Clostridium difficile </it>toxin-induced enteritis is characterized by exuberant intestinal tissue inflammation, epithelial disruption and diarrhea. Adenosine, through its action on the adenosine A_2Areceptor, prevents neutrophillic adhesion and oxidative burst and inhibits inflammatory cytokine production. Alanyl-glutamine enhances intestinal mucosal repair and decreases apoptosis of enterocytes. This study investigates the protection from enteritis by combination therapy with ATL 370, an adenosine A_2Areceptor agonist, and alanyl-glutamine in a rabbit and murine intestinal loop models of <it>C. difficile </it>toxin A-induced epithelial injury.</p> <p>Methods</p> <p>Toxin A with or without alanyl-glutamine was administered intraluminally to rabbit ileal or murine cecal loops. Animals were also given either PBS or ATL 370 parenterally. Ileal tissues were examined for secretion, histopathology, apoptosis, Cxcl1/KC and IL-10.</p> <p>Results</p> <p>ATL 370 decreased ileal secretion and histopathologic changes in loops treated with Toxin A. These effects were reversed by the A_2Areceptor antagonist, SCH 58261, in a dose-dependent manner. The combination of ATL 370 and alanyl-glutamine significantly further decreased ileal secretion, mucosal injury and apoptosis more than loops treated with either drug alone. ATL 370 and alanyl-glutamine also decreased intestinal tissue KC and IL-10.</p> <p>Conclusions</p> <p>Combination therapy with an adenosine A_2Areceptor agonist and alanyl-glutamine is effective in reversing <it>C. difficile </it>toxin A-induced epithelial injury, inflammation, secretion and apoptosis in animals and has therapeutic potential for the management of <it>C. difficile </it>infection.</p

Variations in TcdB Activity and the Hypervirulence of Emerging Strains of Clostridium difficile

Hypervirulent strains of Clostridium difficile have emerged over the past decade, increasing the morbidity and mortality of patients infected by this opportunistic pathogen. Recent work suggested the major C. difficile virulence factor, TcdB, from hypervirulent strains (TcdBHV) was more cytotoxic in vitro than TcdB from historical strains (TcdBHIST). The current study investigated the in vivo impact of altered TcdB tropism, and the underlying mechanism responsible for the differences in activity between the two forms of this toxin. A combination of protein sequence analyses, in vivo studies using a Danio rerio model system, and cell entry combined with fluorescence assays were used to define the critical differences between TcdBHV and TcdBHIST. Sequence analysis found that TcdB was the most variable protein expressed from the pathogenicity locus of C. difficile. In line with these sequence differences, the in vivo effects of TcdBHV were found to be substantially broader and more pronounced than those caused by TcdBHIST. The increased toxicity of TcdBHV was related to the toxin's ability to enter cells more rapidly and at an earlier stage in endocytosis than TcdBHIST. The underlying biochemical mechanism for more rapid cell entry was identified in experiments demonstrating that TcdBHV undergoes acid-induced conformational changes at a pH much higher than that of TcdBHIST. Such pH-related conformational changes are known to be the inciting step in membrane insertion and translocation for TcdB. These data provide insight into a critical change in TcdB activity that contributes to the emerging hypervirulence of C. difficile

Health Aspects of the Pre-Departure Phase of Migration

In the second article in a six-part PLoS Medicine series on Migration & Health, Brian Gushulak and Douglas MacPherson discuss the pre-departure phase of migration and the specific health risks and policy needs associated with this phase