Mathematically optimal decisions in forensic age assessment

Forensic age estimation generally involves considerable amounts of uncertainty. Forensic age indicators such as teeth or skeleton images predict age only approximately, and this is likely to remain true even for future forensic age indicators. Thus, forensic age assessment should aim to make the best possible decisions under uncertainty. In this paper, we apply mathematical theory to make statistically optimal decisions to age assessment. Such an application is fairly straightforward assuming there is a standardized procedure for obtaining age indicator information from individuals, assuming we have data from the application of this procedure to a group of persons with known ages, and assuming the starting point for each individual is a probability distribution describing prior knowledge about the persons age. The main problem is then to obtain such a prior. Our analysis indicates that individual priors rather than a common prior for all persons may be necessary. We suggest that caseworkers, based on individual case information, may select a prior from a menu of priors. We show how information may then be collected over time to gradually increase the robustness of the decision procedure. We also show how replacing individual prior distributions for age with individual prior odds for being above an age limit cannot be recommended as a general method. Our theoretical framework is applied to data where the maturity of the distal femur and the third molar is observed using MRI. As part of this analysis we observe a weak positive conditional correlation between maturity of the two body parts.

     

Susceptibility of Treponema pallidum and other selected spirochaetes to zidovudine.

The antiviral nucleoside derivative zidovudine (3'-azido-3'-deoxythymidine) previously has been shown to be an effective antibacterial agent in animals infected with Escherichia coli or Salmonella typhimurium. Since HIV infection can alter the course of human syphilis with serious consequences, it was of interest to determine if the noncultivable spirochaetal agent of syphilis, Treponema pallidum, is susceptible to this compound. The progression of experimental rabbit syphilis over a three week period was unchanged in animals receiving either 50 or 150 mg/kg oral zidovudine daily. In addition, a number of cultivable pathogenic and nonpathogenic spirochaetes were tested for susceptibility to zidovudine in vitro. At a concentration of 100 mg/L, zidovudine had no detectable effect on spirochaete growth, morphology, or motility. Thus it appears that spirochaetes are generally not susceptible to this compound, and that long-term zidovudine therapy will not be of benefit in preventing or controlling syphilis or other spirochaetoses in HIV-infected humans receiving this drug.     

Identification and purification of a recombinant Treponema pallidum basic membrane protein antigen expressed in Escherichia coli.

A recombinant plasmid designated pLVS3 previously was described that harbored a 14-kilobase insert of Treponema pallidum genomic DNA. Escherichia coli maxicells programmed with this plasmid synthesized three treponemal protein antigens of molecular weights 39,000, 35,000, and 25,000 (39K, 35K, and 25K proteins, respectively). In this study, a detailed deletion analysis of pLVS3 demonstrated that the genetic information for all three protein antigens is contained within a 1.5-kilobase EcoRI-HpaI restriction fragment. The DNA sequence of this fragment revealed a single open reading frame of 361 codons that most likely encodes a signal peptide-bearing precursor to the 39K protein that can be transiently detected in E. coli maxicells. Evidence indicated that the 35K and 25K protein antigens are derivatives of the larger protein and are only produced in maxicells. A significant elevation in expression of the 39K treponemal protein antigen in E. coli was obtained by using the E. coli lpp and lac promoters and a genetic construction in which the signal peptide and first four residues of the "mature" 39K protein were replaced by six amino acids encoded by the vector. This hybrid protein exhibited an unusually high pI, which greatly facilitated its purification to homogeneity. By using antibody prepared against the hybrid protein, the native treponemal protein counterpart, also of molecular weight 39,000, was identified as a membrane component of T. pallidum. Since the native protein also exhibited a net positive charge, it has been designated the T. pallidum basic membrane protein.     

Cellular and extracellular protein antigens of Treponema pallidum synthesized during in vitro incubation of freshly extracted organisms

A new medium that permits radiolabeling of freshly extracted cells of Treponema pallidum with [35S]methionine very efficiently has been devised. Although treponemes were not purified free of contaminating rabbit tissue, label was incorporated exclusively into treponemal protein in a linear manner for at least the first 16 h of in vitro incubation. Throughout this period, virtually a full complement of treponemal proteins was synthesized, based on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis comparison of the radiolabeled protein profile with the Coomassie blue-stained profile of gradient-purified treponemes. The radiolabeled protein profiles obtained with three pathogenic strains were very similar but not identical. Using solubilized treponemal extracts and a sensitive radioimmunoprecipitation procedure, we identified the protein antigens of T. pallidum that were recognized by immunoglobulin G antibodies in various rabbit and human syphilitic sera. A simple fractionation procedure has been used to separate soluble and membrane-bound treponemal proteins. A number of the membrane proteins are exposed on the cell surface, since intact radiolabeled treponemes bound antibodies directed against these proteins. In addition, a unique class of low-molecular-weight extracellular treponemal proteins has been identified. The cell surface-exposed proteins were among the earliest proteins recognized by immunoglobulin G antibodies after experimental infection of rabbits with T. pallidum.     

Pregnant Women Living with HIV (WLH) Supported at Clinics by Peer WLH: A Cluster Randomized Controlled Trial

Throughout Africa, Peer Mentors who are women living with HIV (WLH) are supporting pregnant WLH at antenatal and primary healthcare clinics (McColl in BMJ 344:e1590, 2012). We evaluate a program using this intervention strategy at 1.5 months post-birth. In a cluster randomized controlled trial in KwaZulu-Natal, South Africa, eight clinics were randomized for their WLH to receive either: standard care (SC), based on national guidelines to prevent mother-to-child transmission (4 clinics; n = 656 WLH); or an enhanced intervention (EI; 4 clinics; n = 544 WLH). The EI consisted of four antenatal and four postnatal small group sessions led by Peer Mentors, in addition to SC. WLH were recruited during pregnancy and 70 % were reassessed at 1.5 months post-birth. EI’s effect was ascertained on 16 measures of maternal and infant well-being using random effects regressions to control for clinic clustering. A binomial test for correlated outcomes evaluated EI’s overall effectiveness. Among EI WLH reassessed, 87 % attended at least one intervention session (mean 4.1, SD 2.0). Significant overall benefits were found in EI compared to SC using the binomial test. However, it is important to note that EI WLH were significantly less likely to adhere to ARV during pregnancy compared to SC. Secondarily, compared to SC, EI WLH were more likely to ask partners to test for HIV, better protected their infants from HIV transmission, and were less likely to have depressed mood and stunted infants. Adherence to clinic intervention groups was low, yet, there were benefits for maternal and infant health at 1.5 months post-birth.     

Sexual orientation and health: comparisons in the women's health initiative sample

CONTEXT: Little is known about older lesbian and bisexual women. Existing research rarely compares characteristics of these women with comparable heterosexual women. OBJECTIVE: To compare heterosexual and nonheterosexual women 50 to 79 years on specific demographic characteristics, psychosocial risk factors, screening practices, and other health-related behaviors associated with increased risk for developing particular diseases or disease outcomes. DESIGN: Analysis of data from 93,311 participants in the Women's Health Initiative (WHI) study of health in postmenopausal women, comparing characteristics of 5 groups: heterosexuals, bisexuals, lifetime lesbians, adult lesbians, and those who never had sex as an adult. SETTING: Subjects were recruited at 40 WHI study centers nationwide representing a range of geographic and ethnic diversity. PARTICIPANTS: Postmenopausal women aged 50 to 79 years who met WHI eligibility criteria, signed an informed consent to participate in the WHI clinical trial(s) or observational study, and responded to the baseline questions on sexual orientation. MAIN OUTCOME MEASURES: Demographic characteristics, psychosocial risk factors, recency of screening tests, and other health-related behaviors as assessed on the WHI baseline questionnaire. RESULTS: Although of higher socioeconomic status than the heterosexuals, the lesbian and bisexual women more often used alcohol and cigarettes, exhibited other risk factors for reproductive cancers and cardiovascular disease, and scored lower on measures of mental health and social support. Notable is the 35% of lesbians and 81% of bisexual women who have been pregnant. Women reporting that they never had sex as an adult had lower rates of Papanicolaou screening and hormone replacement therapy use than other groups. CONCLUSIONS: This sample of older lesbian and bisexual women from WHI shows many of the same health behaviors, demographic, and psychosocial risk factors reported in the literature for their younger counterparts, despite their higher socioeconomic status and access to health care. The lower rates of recommended screening services and higher prevalence of obesity, smoking, alcohol use, and lower intake of fruit and vegetables among these women compared with heterosexual women indicate unmet needs that require effective interactions between care providers and nonheterosexual women.     

Osteoporosis and rate of bone loss among postmenopausal survivors of breast cancer

BACKGROUND: Breast cancer diagnosis and treatment may put women at higher risk for osteoporosis in later life. METHODS: In a subgroup of participants in the Women's Health Initiative Observational Study, authors of the current study investigated differences in bone mineral density (BMD, measured by dual-energy x-ray absorptiometry) between breast cancer survivors (n = 209) and a noncancer reference group (n = 5759). RESULTS: In comparison to the reference group, breast cancer survivors had significantly lower total body BMD value (0.989 vs. 1.013 g/cm(2), P = 0.001) and total hip BMD value (0.823 vs. 0.845 g/cm(2), P = 0.02) at baseline after adjustment for age, race/ethnicity, years since menopause, and clinical center. These lower BMD levels were largely explained by lower usage of hormone therapy (HT) among survivors: after additional statistical adjustment for HT, hip BMD values were 0.834 versus 0.844 g/cm(2) (P = 0.26), and total body values were 1.005 versus 1.013 g/cm(2) (P = 0.33) for survivors and reference women, respectively. More than 77% of survivors with osteoporosis were undiagnosed by their healthcare providers, and this was similar to the undiagnosed rate in the reference group (85.7%). Longitudinally, breast cancer survivors in this study did not demonstrate an accelerated rate of bone loss compared with the reference population. CONCLUSIONS: Associated with lower HT usage, postmenopausal survivors of breast cancer were more likely to have low BMD in comparison to other women of the same age; and many of these survivors with osteoporosis were undiagnosed.     

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial

Context  Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. Objective  To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. Intervention  Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. Main Outcome Measures  The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. Results  In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. Conclusions  The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.      

Effect of an integrated nutrition curriculum on medical education, student clinical performance, and student perception of medical-nutrition training

BACKGROUND: Ninety-eight percent of medical schools report nutrition as a component of medical education. However, most schools do not have an identifiable nutrition curriculum. Medical schools that do include nutrition have not evaluated its effect on clinical skills. OBJECTIVE: The objective was to determine the efficacy of an integrated undergraduate medical curriculum to increase the quantity of nutrition instruction and to advance nutrition clinical skills demonstrated by medical students. DESIGN: A quasiexperimental design was constructed to determine whether an integrated nutrition curriculum increased the performance on nutrition-oriented clinical examinations of medical school classes that received 1, 2, or 3 y of the curriculum. The evaluation of the curriculum focused on 3 areas: 1) hours of nutrition instruction, 2) the application of nutrition within a clinical setting, and 3) perceptions about the nutrition curriculum. The Objective Structured Clinical Examination (OSCE) nutrition score was compared between graduating classes by use of analysis of variance. Data from the American Association of Medical Colleges were analyzed to determine the change in the proportion of students who reported that the amount of time devoted to nutrition was adequate. RESULTS: The implementation of the integrated nutrition curriculum resulted in a doubling of the total hours of required instruction in the medical curriculum (35 compared with 75 h). The mean (+/-1 SEM) OSCE nutrition score significantly improved after the implementation of the curriculum (41.7 +/- 0.9% compared with 50.6 +/- 1.1%) and the percentage of students who reported that the amount of nutrition taught during medical school was inadequate decreased (68.4% compared with 11.5%). CONCLUSION: Medical students improved their clinical nutrition practice skills through participation in an integrated nutrition curriculum.     

The cervical cap

The cervical cap is a barrier contraceptive method with an efficacy similar to that of the diaphragm. It has several advantages over other barrier contraceptives. In particular, it can be left in place for up to 48 hours, and repeated applications of spermicide are not necessary, even if sexual intercourse occurs more than once. In addition, the side effects seen with other barrier methods do not occur with the cervical cap. In some women, Papanicolaou tests may become abnormal, especially during the first three months of cap use. Therefore, careful monitoring of cervical cap users is essential.