Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years - Relationships to hormone replacement therapy

Hormone replacement therapy (HRT) has been shown to increase the relative risk of idiopathic venous thromboembolism (VTE) about threefold in several observational studies and one randomised controlled trial. Whether or not this relative risk is higher in women with underlying thrombophilia phenotypes, such as activated protein C (APC) resistance, is unknown. We therefore restudied the participants in a case-control study of the relationship between the use of HRT and the occurrence of idiopathic VTE in women aged 45-64 years. After protocol exclusions, 66 of the cases in the original study and 163 of the controls were studied. Twenty haematological variables relevant to risk of VTE were analysed, including thrombotic states defined from the literature. The relative risk of VTE showed significant associations with APC resistance (OR 4.06; 95% CI 1.62, 10.21); low antithrombin (3.33; 1.15, 9.65) or protein C (2.93; 1.06, 8.14); and high coagulation factor IX (2.34: 1.26, 1.35), or fibrin D-dimer (3.84; 1.99, 7.32). HRT use increased the risk of VTE in women without any of these thrombotic static; (OR 4.09; 95% CI 1.26, 13.30). A similar effect of HRT use on the relative risk of VTE was also found in women with prothrombotic states. Thus for example, the combination of HRT use and APC resistance increased the risk of VTE about 13-fold compared with women of similar age without either APC resistance or HRT use (OR 13.27; 95%, CI 4.30, 40.97). We conclude that the combination of HRT use and thrombophilias (especially if multiple) increases the relative risk of VTE substantially; hence women known to have thrombophilias (especially if multiple) should be counselled about this increased risk prior to prescription of HRT. However. HRT increases the risk of VTE about fourfold even in women without any thrombotic abnormalities: possible causes are discussed

MintHint: Automated Synthesis of Repair Hints

Being able to automatically repair programs is an extremely challenging task. In this paper, we present MintHint, a novel technique for program repair that is a departure from most of today's approaches. Instead of trying to fully automate program repair, which is often an unachievable goal, MintHint performs statistical correlation analysis to identify expressions that are likely to occur in the repaired code and generates, using pattern-matching based synthesis, repair hints from these expressions. Intuitively, these hints suggest how to rectify a faulty statement and help developers find a complete, actual repair. MintHint can address a variety of common faults, including incorrect, spurious, and missing expressions. We present a user study that shows that developers' productivity can improve manyfold with the use of repair hints generated by MintHint -- compared to having only traditional fault localization information. We also apply MintHint to several faults of a widely used Unix utility program to further assess the effectiveness of the approach. Our results show that MintHint performs well even in situations where (1) the repair space searched does not contain the exact repair, and (2) the operational specification obtained from the test cases for repair is incomplete or even imprecise

Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis

Hormone replacement therapy (HRT) increases the risk of venous thrombosis. We investigated whether this risk is affected by carriership of hereditary prothrombotic abnormalities. Therefore, we determined the two most common prothrombotic mutations, factor V Leiden and prothrombin 20210A in women who participated in a case-control study on venous thrombosis. Relative risks were expressed as odds ratios (OR) with 95% confidence intervals (CI95). Among 7 7 women aged 45-64 years with a first venous thrombosis, 51% were receiving HRT at the time of thrombosis, compared with 24% of control women (OR = 3.3, CI95 1.8-5.8). Among the patients, 23% had a prothrombotic defect, versus 7% among the control women (OR = 3.8, CI95 1.7- 8.5). Women who had factor V Leiden and used HRT had a 15-fold increased risk (OR = 15.5, CI95 3.1-77), which exceeded the expected joint odds ratio of 6.1 (under an additive model). We conclude that the thrombotic risk of HRT may particularly affect women with prothrombotic mutations. Efforts to avoid HRT in women with increased risk of thrombosis are advisable

Sphingosine protects aging hearts from ischemia/reperfusion injury: Superiority to sphingosine 1-phosphate and ischemic pre- and post-conditioning

Aging hearts are known to have diminished capacity to be protected against reoxygenation ischemia/reperfusion (IR) injury provided by various cardioprotective regimens. In search of a more successful regimen, we have studied the response of aged hearts to preconditioning (PC) and postconditioning (POST) elicited by sphingosine or sphingosine 1-phosphate treatment

Identifying the "Right Stuff": An Exploration-Focused Astronaut Job Analysis

Industrial and organizational (I/O) psychologists play a key role in NASA astronaut candidate selection through the identification of the competencies necessary to successfully engage in the astronaut job. A set of psychosocial competencies, developed by I/O psychologists during a prior job analysis conducted in 1996 and updated in 2003, were identified as necessary for individuals working and living in the space shuttle and on the International Space Station (ISS). This set of competencies applied to the space shuttle and applies to current ISS missions, but may not apply to longer-duration or long-distance exploration missions. With the 2015 launch of the first 12- month ISS mission and the shift in the 2020s to missions beyond low earth orbit, the type of missions that astronauts will conduct and the environment in which they do their work will change dramatically, leading to new challenges for these crews. To support future astronaut selection, training, and research, I/O psychologists in NASA's Behavioral Health and Performance (BHP) Operations and Research groups engaged in a joint effort to conduct an updated analysis of the astronaut job for current and future operations. This project will result in the identification of behavioral competencies critical to performing the astronaut job, along with relative weights for each of the identified competencies, through the application of job analysis techniques. While this job analysis is being conducted according to job analysis best practices, the project poses a number of novel challenges. These challenges include the need to identify competencies for multiple mission types simultaneously, to evaluate jobs that have no incumbents as they have never before been conducted, and working with a very limited population of subject matter experts. Given these challenges, under the guidance of job analysis experts, we used the following methods to conduct the job analysis and identify the key competencies for current and potential future missions

Breast self examination and breast cancer stage at diagnosis.

The relationship between breast self examination (BSE) and breast cancer stage at diagnosis was examined in 616 women aged 15-59 years. Differences in tumour characteristics between those not practising BSE and those practising but not taught were small and inconstant. However, women who had both practised and had been taught BSE had more favourable tumours than the non-practising group. The difference was most marked in terms of tumour size and the involvement of axillary nodes. The proportions of women in the non-BSE and taught-BSE groups with each characteristic were respectively: size less than or equal to 2 cm 33% and 45%, T1 clinical stage 27% and 42%, and N0 pathological stage 37% and 50%. This advantage to taught-BSE women persisted after adjustment for the identified confounding factors of age, social class and oral contraceptive use. The likely impact on breast cancer mortality is difficult to assess, although the potential benefit of the lead time gained must not be ignored when assessing the costs and benefits of BSE

Making Things Right: Nurses' Experiences with Workplace Bullying—A Grounded Theory

While bullying in the healthcare workplace has been recognized internationally, there is still a culture of silence in many institutions in the United States, perpetuating underreporting and insufficient and unproven interventions. The deliberate, repetitive, and aggressive behaviors of bullying can cause psychological and/or physical harm among professionals, disrupt nursing care, and threaten patient safety and quality outcomes. Much of the literature focuses on categories of bullying behaviors and nurse responses. This qualitative study reports on the experiences of nurses confronting workplace bullying. We collected data from the narratives of 99 nurses who completed an open-ended question embedded in an online survey in 2007. A constructivist grounded theory approach was used to analyze the data and shape a theory of how nurses make things right when confronted with bullying. In a four-step process, nurses place bullying in context, assess the situation, take action, and judge the outcomes of their actions. While many nurses do engage in a number of effective yet untested strategies, two additional concerns remain: inadequate support among nursing colleagues and silence and inaction by nurse administrators. Qualitative inquiry has the potential to guide researchers to a greater understanding of the complexities of bullying in the workplace

Fertility in relation to the risk of breast cancer.

All studies reported here, like our own, support the view that the higher risk of breast cancer in women having a late first birth is attributable to early pregnancy itself having a direct protective effect against the disease, a benefit which they have not experienced. One study, however, has directly examined breast cancer risk in two groups of infertile women - those presumed to have 'progesterone deficiency' and those presumed to have infertility of non hormonal origin. The results suggested that breast cancer risk was increased in premenopausal women (but not in postmenopausal women) with 'progesterone deficiency'. The number of cases of premenopausal breast cancer included in the analysis (11) was, however, very small. In our view, the findings in this study do not weigh heavily against our results and those of others

Early oral contraceptive use and breast cancer: results of another case-control study.

We report the results of a case-control study of oral contraceptive use and breast cancer conducted in London, Oxford and Edinburgh between 1980 and 1984. One thousand one hundred and twenty-five women aged 16-64 years with newly diagnosed breast cancer and a like number of matched controls were interviewed and asked about their past due use of oral contraceptives (OCs). Among women aged 45 years or more at diagnosis there was no evidence of an association between OC use and breast cancer. Among the 351 pairs of women aged under 45 years at diagnosis there was a significantly elevated risk associated with increasing duration of use before first full term pregnancy (relative risk for 4+ years use versus never use = 2.6, 95% confidence limits, 1.3-5.4). Since this result is at variance with the findings in some other studies we have investigated the nature of this association with particular emphasis on possible bias, pill type and a latent effect

Analogs: Gateway to Spaceflight Research

No abstract availabl