Influence of prior delivery mode on perineal trauma risk.

OBJECTIVE: To evaluate the impact of a previous pregnancy and delivery on perineal trauma rates in the subsequent vaginal birth. METHODS: Retrospective cohort study. The perineal outcomes of secundiparous women with history of previous (first) delivery in one of three categories: failed operative vaginal delivery (FOVD) and second stage emergency caesarean section (EmCS); elective caesarean section (ELCS), and vaginal delivery (VD) with intact perineum, were compared with a control primiparous group. RESULTS: The percentage OASIs at first vaginal delivery after prior FOVD+EmCS was 17.3%(n=9), 12.9%(n=18) after previous ELCS, and 0.6%(n=9) after prior VD maintaining an intact perineum, compared with 6%(n=1193) in the control primiparous group of women. Multivariate regression analysis demonstrated prior FOVD+EmCS and ELCS were associated with a statistically significant increased risk of OASIs of 180% and 110% when compared to control (odds ratio (OR): 2.80; 95% confidence interval (CI): 1.35-5.78 and OR: 2.10; 95%CI: 1.27-3.48) respectively. Prior VD with intact perineum was associated with a statistically significantly reduced risk of OASIs (OR: 0.09; 95%CI: 0.04-0.17). CONCLUSIONS: Previous FOVD+EmCS and ELCS were associated with increased risk of OASIs in subsequent vaginal delivery compared to control, whilst previous VD with intact perineum was associated with decreased risk

The Statistical Mechanics of Horizons and Black Hole Thermodynamics

Although we know that black holes are characterized by a temperature and an entropy, we do not yet have a satisfactory microscopic ``statistical mechanical'' explanation for black hole thermodynamics. I describe a new approach that attributes the thermodynamic properties to ``would-be gauge'' degrees of freedom that become dynamical on the horizon. For the (2+1)-dimensional black hole, this approach gives the correct entropy. (Talk given at the Pacific Conference on Gravitation and Cosmology, Seoul, February 1996.)Comment: 11 pages, LaTe

Gravitational Radiation from Post-Newtonian Sources and Inspiralling Compact Binaries

The article reviews the current status of a theoretical approach to the problem of the emission of gravitational waves by isolated systems in the context of general relativity. Part A of the article deals with general post-Newtonian sources. The exterior field of the source is investigated by means of a combination of analytic post-Minkowskian and multipolar approximations. The physical observables in the far-zone of the source are described by a specific set of radiative multipole moments. By matching the exterior solution to the metric of the post-Newtonian source in the near-zone we obtain the explicit expressions of the source multipole moments. The relationships between the radiative and source moments involve many non-linear multipole interactions, among them those associated with the tails (and tails-of-tails) of gravitational waves. Part B of the article is devoted to the application to compact binary systems. We present the equations of binary motion, and the associated Lagrangian and Hamiltonian, at the third post-Newtonian (3PN) order beyond the Newtonian acceleration. The gravitational-wave energy flux, taking consistently into account the relativistic corrections in the binary moments as well as the various tail effects, is derived through 3.5PN order with respect to the quadrupole formalism. The binary's orbital phase, whose prior knowledge is crucial for searching and analyzing the signals from inspiralling compact binaries, is deduced from an energy balance argument.Comment: 109 pages, 1 figure; this version is an update of the Living Review article originally published in 2002; available on-line at http://www.livingreviews.org

Expanding role of the internet in the orthopaedic outpatient setting

The number of patients requiring review after joint arthroplasty is increasing. With an ageing population, increasing expectations from patients, and improved diagnostic methods and treatments, the demand for these procedures will also increase.1 The Department of Orthopaedic Surgery at Royal Devon and Exeter Hospital (Exeter, UK) started to experience a backlog of long-term arthroplasty patients requiring follow-up owing to limited outpatient resources and clinical staff. This scenario led us to think about other ways of reviewing these patients and to explore the feasibility of ‘virtual’ follow-ups. In 2002, Gupte and colleagues reviewed Internet use in the setting of orthopaedic outpatient clinics. They investigated the: (i) prevalence of Internet use; (ii) perception of the quality of medical information provided by the Internet; (iii) future intentions and attitudes towards Internet-based consultations.2 Their study showed promising data about the potential use of Internet-based follow-up, concluding that more than half of the patients evaluated were willing to access the Internet for medical information, with younger patients more likely to do so. Moreover, a significant proportion of respondents were willing to undergo an Internet-based consultation. The decade between the study by Gupte and colleagues and the present study has seen huge expansion in the use and availability of the Internet in the domestic setting. In 2002, a poll by the UK Office of National Statistics (ONS) concluded that 46% of UK households had an Internet connection. In 2011, ONS data showed that 77% of UK homes had an active internet connection.3 This rise has continued and, in 2014, 84% of individuals used the internet and 76% of adults accessed the internet each day.4 In addition, the way in which individuals access the internet is evolving, with 45% of internet users now accessing it via mobile devices. An estimated 6 million people accessed the internet via a mobile device for the first time in 2011.3 With the huge growth in internet availability in the past decade, we aimed to: (i) ascertain how use, attitudes and perceptions of the internet have changed over this time; (ii) explore potential uses and problems of internet follow-up in a patient cohort; (iii) ascertain if patients had access to an email account and, if so, would consider using an email-based questionnaire on follow-up; (iv) discover if individuals who did not have direct access to the internet had friends or relatives who did, and whether they would be willing to engage in follow-up by ‘proxy’.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Optimal control models of the goal-oriented human locomotion

In recent papers it has been suggested that human locomotion may be modeled as an inverse optimal control problem. In this paradigm, the trajectories are assumed to be solutions of an optimal control problem that has to be determined. We discuss the modeling of both the dynamical system and the cost to be minimized, and we analyze the corresponding optimal synthesis. The main results describe the asymptotic behavior of the optimal trajectories as the target point goes to infinity

Nuclear Receptors and the Warburg effect in cancer

In 1927 Otto Warburg established that tumours derive energy primarily from the conversion of glucose to lactic acid and only partially through cellular respiration involving oxygen. In the 1950’s he proposed that all causes of cancer reflected different mechanisms of disabling cellular respiration in favour of fermentation (now termed aerobic glycolysis). The role of aberrant glucose metabolism in cancer is now firmly established. The shift away from oxidative phosphorylation towards the metabolically expensive aerobic glycolysis is somewhat counter-intuitive given its wasteful nature. Multiple control processes are in place to maintain cellular efficiency and it is likely that these mechanisms are disrupted to facilitate the shift to the reliance on aerobic glycolysis. One such process of cell control is mediated by the nuclear receptor superfamily. This large family of transcription factors plays a significant role in sensing environmental cues and controlling decisions on proliferation, differentiation and cell death for example, to regulate glucose uptake and metabolism and to modulate the actions of oncogenes and tumour suppressors. In this review we highlight mechanisms by which nuclear receptors actions are altered during tumorigenic transformation and can serve to enhance the shift to aerobic glycolysis. At the simplest level, a basic alteration in NR behaviour can serve to enhance glycolytic flux thus providing a basis for enhanced survival within the tumour micro-environment. Ameliorating the enhanced NR activity in this context may help to sensitize cancer cells to Warburg targeted therapies and may provide future drug targets

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

Combination of electroweak and QCD corrections to single W production at the Fermilab Tevatron and the CERN LHC

Precision studies of the production of a high-transverse momentum lepton in association with missing energy at hadron colliders require that electroweak and QCD higher-order contributions are simultaneously taken into account in theoretical predictions and data analysis. Here we present a detailed phenomenological study of the impact of electroweak and strong contributions, as well as of their combination, to all the observables relevant for the various facets of the p\smartpap \to {\rm lepton} + X physics programme at hadron colliders, including luminosity monitoring and Parton Distribution Functions constraint, $W$ precision physics and search for new physics signals. We provide a theoretical recipe to carefully combine electroweak and strong corrections, that are mandatory in view of the challenging experimental accuracy already reached at the Fermilab Tevatron and aimed at the CERN LHC, and discuss the uncertainty inherent the combination. We conclude that the theoretical accuracy of our calculation can be conservatively estimated to be about 2% for standard event selections at the Tevatron and the LHC, and about 5% in the very high $W$ transverse mass/lepton transverse momentum tails. We also provide arguments for a more aggressive error estimate (about 1% and 3%, respectively) and conclude that in order to attain a one per cent accuracy: 1) exact mixed ${\cal O}(\alpha \alpha_s)$ corrections should be computed in addition to the already available NNLO QCD contributions and two-loop electroweak Sudakov logarithms; 2) QCD and electroweak corrections should be coherently included into a single event generator.Comment: One reference added. Final version to appear in JHE

Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)