Left-right breast asymmetry and risk of screen-detected and interval cancers in a large population-based screening population

OBJECTIVES: To assess the associations between automated volumetric estimates of mammographic asymmetry and breast cancers detected at the same ("contemporaneous") screen, at subsequent screens, or in between (interval cancers). METHODS: Automated measurements from mammographic images (N = 79,731) were used to estimate absolute asymmetry in breast volume (BV) and dense volume (DV) in a large ethnically diverse population of attendees of a UK breast screening programme. Logistic regression models were fitted to assess asymmetry associations with the odds of a breast cancer detected at contemporaneous screen (767 cases), adjusted for relevant confounders.Nested case-control investigations were designed to examine associations between asymmetry and the odds of: (a) interval cancer (numbers of cases/age-matched controls: 153/646) and (b) subsequent screen-detected cancer (345/1438), via conditional logistic regression. RESULTS: DV, but not BV, asymmetry was positively associated with the odds of contemporaneous breast cancer (P-for-linear-trend (Pt) = 0.018). This association was stronger for first (prevalent) screens (Pt = 0.012). Both DV and BV asymmetry were positively associated with the odds of an interval cancer diagnosis (Pt = 0.060 and 0.030, respectively). Neither BV nor DV asymmetry were associated with the odds of having a subsequent screen-detected cancer. CONCLUSIONS: Increased DV asymmetry was associated with the risk of a breast cancer diagnosis at a contemporaneous screen or as an interval cancer. BV asymmetry was positively associated with the risk of an interval cancer diagnosis. ADVANCES IN KNOWLEDGE: The findings suggest that DV and BV asymmetry may provide additional signals for detecting contemporaneous cancers and assessing the likelihood of interval cancers in population-based screening programmes

Are mammography image acquisition factors, compression pressure and paddle tilt, associated with breast cancer detection in screening?

Objectives: To assess the associations between objectively measured mammographic compression pressure and paddle tilt and breast cancer (BC) detected at the same (“contemporaneous”) screen, subsequent screens, or in-between screens (interval cancers). Methods: Automated pressure and paddle tilt estimates were derived for 80,495 mammographic examina-tions in a UK population-based screening programme. Adjusted logistic regression models were fitted to estimate the associations of compression parameters with BC detected at contemporaneous screen (777 cases). Nested case-control designs were used to estimate associations of pressure and tilt with: (a) interval cancer (148 cases/625 age-matched controls) and (b) subsequent screen-detected cancer (344/1436), via condi-tional logistic regression. Results: Compression pressure was negatively associated with odds of BC at contemporaneous screen (odds ratio (OR) for top versus bottom third of the pressure distribution: 0.74; 95% CI 0.60, 0.92; P-for-linear-trend (Pt) = 0.007). There was weak evidence that moderate pressure at screening was associated with lower odds of interval cancer (OR for middle versus bottom third: 0.63; 95% CI 0.38, 1.05; p = 0.079), but no association was found between pressure and the odds of BC at subsequent screen. There was no evidence that paddle tilt was associated with the odds of contemporaneous, subsequent screen or interval cancer detection. Conclusions: Findings are consistent with compression pressure, but not paddle tilt, affecting the performance of mammographic screening by interfering with its ability to detect cancers. Advances in knowledge: Inadequate or excessive compression pressure at screening may contribute to a reduced ability to detect cancers, resulting in a greater number of interval cancer cases

Ethnic and age differences in right-left breast asymmetry in a large population-based screening population

OBJECTIVE: Exposure to sex hormones is important in the pathogenesis of breast cancer and inability to tolerate such exposure may be reflected in increased asymmetrical growth of the breasts. This study aims to characterize, for the first time, asymmetry in breast volume (BV) and radiodense volume (DV) in a large ethnically diverse population. METHODS: Automated measurements from digital raw mammographic images of 54,591 cancer-free participants (aged 47-73) in a UK breast screening programme were used to calculate absolute (cm3) and relative asymmetry in BV and DV. Logistic regression models were fitted to assess asymmetry associations with age and ethnicity. RESULTS: BV and DV absolute asymmetry were positively correlated with the corresponding volumetric dimension (BV or DV). BV absolute asymmetry increased, whilst DV absolute asymmetry decreased, with increasing age (P-for-linear-trend <0.001 for both). Relative to Whites, Blacks had statistically significantly higher, and Chinese lower, BV and DV absolute asymmetries. However, after adjustment for the corresponding underlying volumetric dimension the age and ethnic differences were greatly attenuated. Median relative (fluctuating) BV and DV asymmetry were 2.34 and 3.28% respectively. CONCLUSION: After adjusting for the relevant volumetric dimension (BV or DV), age and ethnic differences in absolute breast asymmetry were largely resolved. ADVANCES IN KNOWLEDGE: Previous small studies have reported breast asymmetry-breast cancer associations. Automated measurements of asymmetry allow the conduct of large-scale studies to further investigate these associations

The mental health of elite athletes: A narrative systematic review

BACKGROUND: The physical impacts of elite sport participation have been well documented; however, there is comparatively less research on the mental health and psychological wellbeing of elite athletes. OBJECTIVE: This review appraises the evidence base regarding the mental health and wellbeing of elite-level athletes, including the incidence and/or nature of mental ill-health and substance use. METHODS: A systematic search of the PubMed, EMBASE, SPORTDiscus, PsycINFO, Cochrane and Google Scholar databases, up to and including May 2015, was conducted. RESULTS: The search yielded a total of 2279 records. Following double screening, 60 studies were included. The findings suggested that elite athletes experience a broadly comparable risk of high-prevalence mental disorders (i.e. anxiety, depression) relative to the general population. Evidence regarding other mental health domains (i.e. eating disorders, substance use, stress and coping) is less consistent. These results are prefaced, however, by the outcome of the quality assessment of the included studies, which demonstrated that relatively few studies (25 %) were well reported or methodologically rigorous. Furthermore, there is a lack of intervention-based research on this topic. CONCLUSION: The evidence base regarding the mental health and wellbeing of elite athletes is limited by a paucity of high-quality, systematic studies. Nonetheless, the research demonstrates that this population is vulnerable to a range of mental health problems (including substance misuse), which may be related to both sporting factors (e.g. injury, overtraining and burnout) and non-sporting factors. More high-quality epidemiological and intervention studies are needed to inform optimal strategies to identify and respond to player mental health needs

Transmission potential, skin inflammatory response, and parasitism of symptomatic and asymptomatic dogs with visceral leishmaniasis

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis in Brazil is caused by the protozoan <it>Leishmania (Leishmania) chagasi </it>and it is transmitted by sandfly of the genus <it>Lutzomyia</it>. Dogs are an important domestic reservoir, and control of the transmission of visceral leishmaniasis (VL) to humans includes the elimination of infected dogs. However, though dogs are considered to be an important element in the transmission cycle of <it>Leishmania</it>, the identification of infected dogs representing an immediate risk for transmission has not been properly evaluated. Since it is not possible to treat infected dogs, they are sacrificed when a diagnosis of VL is established, a measure that is difficult to accomplish in highly endemic areas. In such areas, parameters that allow for easy identification of reservoirs that represents an immediate risk for transmission is of great importance for the control of VL transmission. In this study we aimed to identify clinical parameters, reinforced by pathological parameters that characterize dogs with potential to transmit the parasite to the vector.</p> <p>Results</p> <p>The major clinical manifestations of visceral leishmaniasis in dogs from an endemic area were onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. The transmission potential of these dogs was assessed by xenodiagnosis using <it>Lutzomyia longipalpis</it>. Six of nine symptomatic dogs were infective to <it>Lutzomyia longipalpis </it>while none of the five asymptomatic dogs were infective to the sandfly. <it>Leishmania </it>amastigotes were present in the skin of all clinically symptomatic dogs, but absent in asymptomatic dogs. Higher parasite loads were observed in the ear and ungueal region, and lower in abdomen. The inflammatory infiltrate was more intense in the ears and ungueal regions of both symptomatic and asymptomatic dogs. In clinically affected dogs in which few or none <it>Leishmania </it>amastigotes were observed, the inflammatory infiltrate was constituted mainly of lymphocytes and macrophages. When many parasites were present, the infiltrate was also comprised of lymphocytes and macrophages, as well as a larger quantity of polymorphonuclear neutrophils (PMNs).</p> <p>Conclusion</p> <p>Dogs that represent an immediate risk for transmission of <it>Leishmania </it>in endemic areas present clinical manifestations that include onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. Lymphadenopathy in particular was a positive clinical hallmark since it was closely related to the positive xenodiagnosis.</p

A critical look at studies applying over-sampling on the TPEHGDB dataset

Preterm birth is the leading cause of death among young children and has a large prevalence globally. Machine learning models, based on features extracted from clinical sources such as electronic patient files, yield promising results. In this study, we review similar studies that constructed predictive models based on a publicly available dataset, called the Term-Preterm EHG Database (TPEHGDB), which contains electrohysterogram signals on top of clinical data. These studies often report near-perfect prediction results, by applying over-sampling as a means of data augmentation. We reconstruct these results to show that they can only be achieved when data augmentation is applied on the entire dataset prior to partitioning into training and testing set. This results in (i) samples that are highly correlated to data points from the test set are introduced and added to the training set, and (ii) artificial samples that are highly correlated to points from the training set being added to the test set. Many previously reported results therefore carry little meaning in terms of the actual effectiveness of the model in making predictions on unseen data in a real-world setting. After focusing on the danger of applying over-sampling strategies before data partitioning, we present a realistic baseline for the TPEHGDB dataset and show how the predictive performance and clinical use can be improved by incorporating features from electrohysterogram sensors and by applying over-sampling on the training set

Influence of shear stress magnitude and direction on atherosclerotic plaque composition

British Heart Foundation (BHF) grants (no. RG/11/13/29055 and PG/15/49/31595), awarded to R.K. and E.P. who are employed by Bioengineering and the MRC Clinical Sciences Centre at Imperial College London. The grants also supported R.M.P. and S.M.B. V.V.M. was supported by a BHF. PhD studentship

The Plasmodium falciparum, Nima-related kinase Pfnek-4: a marker for asexual parasites committed to sexual differentiation

&lt;b&gt;Background&lt;/b&gt; Malaria parasites undergo, in the vertebrate host, a developmental switch from asexual replication to sexual differentiation leading to the formation of gametocytes, the only form able to survive in the mosquito vector. Regulation of the onset of the sexual phase remains largely unknown and represents an important gap in the understanding of the parasite's complex biology. &lt;b&gt;Methods:&lt;/b&gt; The expression and function of the Nima-related kinase Pfnek-4 during the early sexual development of the human malaria parasite Plasmodium falciparum were investigated, using three types of transgenic Plasmodium falciparum 3D7 lines: (i) episomally expressing a Pfnek-4-GFP fusion protein under the control of its cognate pfnek-4 promoter; (ii) episomally expressing negative or positive selectable markers, yeast cytosine deaminase-uridyl phosphoribosyl transferase, or human dihydrofolate reductase, under the control of the pfnek-4 promoter; and (iii) lacking a functional pfnek-4 gene. Parasite transfectants were analysed by fluorescence microscopy and flow cytometry. In vitro growth rate and gametocyte formation were determined by Giemsa-stained blood smears. &lt;b&gt;Results:&lt;/b&gt; The Pfnek-4-GFP protein was found to be expressed in stage II to V gametocytes and, unexpectedly, in a subset of asexual-stage parasites undergoing schizogony. Culture conditions stimulating gametocyte formation resulted in significant increase of this schizont subpopulation. Moreover, sorted asexual parasites expressing the Pfnek-4-GFP protein displayed elevated gametocyte formation when returned to in vitro culture in presence of fresh red blood cells, when compared to GFP- parasites from the same initial population. Negative selection of asexual parasites expressing pfnek-4 showed a marginal reduction in growth rate, whereas positive selection caused a marked reduction in parasitaemia, but was not sufficient to completely abolish proliferation. Pfnek-4- clones are not affected in their asexual growth and produced normal numbers of stage V gametocytes. &lt;b&gt;Conclusions:&lt;/b&gt; The results indicate that Pfnek-4 is not strictly gametocyte-specific, and is expressed in a small subset of asexual parasites displaying high rate conversion to sexual development. Pfnek-4 is not required for erythrocytic schizogony and gametocytogenesis. This is the first study to report the use of a molecular marker for the sorting of sexually-committed schizont stage P. falciparum parasites, which opens the way to molecular characterization of this pre-differentiated subpopulation