Accelerating wheat breeding for end-use quality with multi-trait genomic predictions incorporating near infrared and nuclear magnetic resonance-derived phenotypes.

KEY MESSAGE: Using NIR and NMR predictions of quality traits overcomes a major barrier for the application of genomic selection to accelerate improvement in grain end-use quality traits of wheat. Grain end-use quality traits are among the most important in wheat breeding. These traits are difficult to breed for, as their assays require flour quantities only obtainable late in the breeding cycle, and are expensive. These traits are therefore an ideal target for genomic selection. However, large reference populations are required for accurate genomic predictions, which are challenging to assemble for these traits for the same reasons they are challenging to breed for. Here, we use predictions of end-use quality derived from near infrared (NIR) or nuclear magnetic resonance (NMR), that require very small amounts of flour, as well as end-use quality measured by industry standard assay in a subset of accessions, in a multi-trait approach for genomic prediction. The NIR and NMR predictions were derived for 19 end-use quality traits in 398 accessions, and were then assayed in 2420 diverse wheat accessions. The accessions were grown out in multiple locations and multiple years, and were genotyped for 51208 SNP. Incorporating NIR and NMR phenotypes in the multi-trait approach increased the accuracy of genomic prediction for most quality traits. The accuracy ranged from 0 to 0.47 before the addition of the NIR/NMR data, while after these data were added, it ranged from 0 to 0.69. Genomic predictions were reasonably robust across locations and years for most traits. Using NIR and NMR predictions of quality traits overcomes a major barrier for the application of genomic selection for grain end-use quality traits in wheat breeding.

Meconium exposure and autism risk.

OBJECTIVE: This study aims to determine whether fetal meconium passage is associated with autism. STUDY DESIGN: This retrospective birth cohort analysis of 9 945 896 children born in California 1991 to 2008 linked discharge diagnosis and procedure codes for prenatal stressors, meconium-stained amniotic fluid (MSAF) and meconium aspiration syndrome (MAS) with autism diagnoses for 47 277 children through 2012. We assessed the relative risk of autism by meconium status using logistic regression, adjusting for demographic and clinical features. RESULTS: Children exposed to meconium (MSAF and MAS) were more likely to be diagnosed with autism in comparison with unexposed children (0.60% and 0.52%, vs 0.47%, respectively). In adjusted analyses, there was a small increase in autism risk associated with MSAF exposure (adjusted relative risk (aRR) 1.18, 95% confidence interval (CI) 1.12 to 1.25), and a marginal association that failed to achieve significance between MAS and autism (aRR 1.08, 95% CI 0.98 to 1.20). CONCLUSION: Resuscitation of neonates with respiratory compromise from in utero meconium exposure may mitigate long-term neurodevelopmental damage.

Scaling of the surface vasculature on the human placenta.

The networks of veins and arteries on the chorionic plate of the human placenta are analyzed in terms of Voronoi cells derived from these networks. Two groups of placentas from the United States are studied: a population cohort with no prescreening, and a cohort from newborns with an elevated risk of developing autistic spectrum disorder. Scaled distributions of the Voronoi cell areas in the two cohorts collapse onto a single distribution, indicating common mechanisms for the formation of the complete vasculatures, but which have different levels of activity in the two cohorts.

Evaluation of ofloxacin in the treatment of laparoscopically documented acute pelvic inflammatory disease (salpingitis).

OBJECTIVE: To evaluate the safety and efficacy of intravenous and oral ofloxacin monotherapy in the treatment of laparoscopically documented acute pelvic inflammatory disease (PID). METHODS: This study was conducted as an open-label, phase-III, uncontrolled, multicenter study. Patients identified with laparoscopic findings of salpingitis were treated with 400 mg of intravenous ofloxacin every 12 hours followed by 400 mg of oral ofloxacin every 12 hours for 10 to 14 days. Patients were evaluated five times for clinical and microbial efficacy. Since laparoscopy was performed only at admission, pathogens identified laparoscopically were presumed eradicated if they were present on the laparoscopic culture and the patient was clinically cured or improved at final evaluation. RESULTS: Of the 70 patients evaluable for safety (intent-to-treat population), the mean age was 25.6 years. Sixty-one of 70 patients (87%) were cured, one improved, one did not improve, and seven were unevaluable because they discontinued study participation. Fifty-one were evaluable for clinical efficacy: 50 (98%) were cured and one did not improve. Sixteen were evaluable for expanded microbiological efficacy: three had documented Neisseria gonorrhoeae; 12, Chlamydia trachomatis; and one, a mixed infection of both organisms. All cervical, laparoscopic, and endometrial cultured pathogens, including N. gonorrhoeae and C. trachomatis, were eradicated or presumed eradicated at the posttherapy visit. No serious or unexpected adverse events occurred. CONCLUSIONS: Ofloxacin monotherapy was effective and well tolerated in the treatment of laparoscopically proven PID in a geographically diverse population. Future studies are necessary to evaluate long-term outcomes and sequelae of PID treatment with single agent therapy.

Anaerobes in pelvic inflammatory disease: implications for the Centers for Disease Control and Prevention's guidelines for treatment of sexually transmitted diseases.

In preparing the 1998 sexually transmitted disease treatment guidelines of the Centers for Disease Control and Prevention, we reviewed evidence regarding the need to eradicate anaerobes when treating pelvic inflammatory disease (PID). Anaerobes are present in the upper genital tract during an episode of acute PID, with the prevalence dependent on the population under study. Vaginal anaerobes can facilitate acquisition of PID and cause tissue damage to the fallopian tube, either directly or indirectly through the host inflammatory response. Use of several broad-spectrum regimens appears to result in excellent clinical cure rates, despite the fact that some combinations fall short of providing comprehensive coverage of anaerobes. There are limited data on the long-term effects of failing to eradicate anaerobes from the upper genital tract. Concern that tissue damage may continue when anaerobes are suboptimally treated has prompted many experts to caution that therapeutic regimens should include comprehensive anaerobic coverage for optimal treatment of women with PID.

Preeclampsia. A nested, case-control study of risk factors and their interactions.

OBJECTIVE: To study the risk factors for preeclampsia and their interactions. STUDY DESIGN: We used a nested, case-control study design to analyze data collected in the Delivery Interview Program, 1977-1980, Boston Hospital for Women (now known as the Brigham and Women's Hospital), Boston. Cases (n = 386) of obstetrician-diagnosed preeclampsia were compared with randomly selected controls (n = 2,355). Using multiple logistic regression, we derived maximum likelihood estimates of adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The following risk factors were statistically significantly associated with preeclampsia: urinary tract infection (UTI) during pregnancy (OR 1.6, 95% CI 1.1-2.5), primiparity (OR 3.8, 95% CI 2.8-5.2), black race (OR 1.5, 95% CI 1.1-1.9), less than a high school education (OR 2.0, 95% CI 1.1-3.6), exposure to diethylstilbestrol in utero (OR 2.4, 95% CI 1.2-2.4), body mass index (kg/m2) > 30 (OR 2.7, 95% CI 1.6-4.4) and cigarette smoking (OR 0.6, 95% CI 0.5-0.8). When evaluating interactions between variables, we found that primiparas who had UTI during pregnancy were five times more likely (OR 5.3, 95% CI 2.9-9.7) to have preeclampsia than were primiparas who did not have UTI during pregnancy. CONCLUSION: It is possible that the preeclampsia associated with some of the risk factors we identified could be modified by the use of prophylactic drugs or other interventions. The primipara with a UTI would be a most likely beneficiary.

Human fetal antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.

Human fetal antibody-dependent cellular cytotoxicity (ADCC) has not been reported previously. Most investigations have failed to document any cytolytic activity among fetal lymphocytes. The purpose of this study was to investigate ADCC activity in the human fetus and identify and characterize the effector cell populations in the fetus. Fetal spleen cells were separated into single-cell suspensions and assayed with 51Cr-labeled herpes simplex 1-infected Chang liver target cells. Significant ADCC activity was detected in 19 of 26 (73%) of freshly assayed fetal spleen cell preparations from fetuses of 17-24 wk gestational age. This activity, however, was significantly less than concurrently run adult peripheral blood mononuclear cells. After plastic adherence the fetal spleen ADCC activity from nonadherent cells was not significantly different from whole spleen preparations. Surprisingly, ADCC activity in nonadherent fetal cells dropped significantly after exposure to latex beads, an effect not seen in nonadherent adult lymphocytes. Thus, either fetal monocyte-derived (macrophages) fetal spleen cells do not efficiently adhere to plastic or a unique nonadherent population of latex-sensitive immunocytes is capable of mediating ADCC activity in the fetus. We suspect the former conclusion to be the more plausible; however, fluorescence-activated cell sorter staining of fetal cells was not sufficient to confirm these suspensions by fluorescence-activated cell sorter analysis.

Pelvic inflammatory disease: metaanalysis of antimicrobial regimen efficacy.

An extensive body of literature has investigated the efficacy of antimicrobial regimens used to treat pelvic inflammatory disease (PID), leaving many clinicians confused about how to choose among them. This study provides a formal appraisal of these reports. Thirty-four treatment studies published between 1966 and 1992 were identified, using Medline and bibliographies, and evaluated qualitatively and quantitatively in a metaanalysis. Twenty-one studies met the criteria for inclusion in this evaluation: appropriate system for making the diagnosis of PID, standardized assessment of clinical outcome, and entry and follow-up evaluation for lower genital tract infection with Neisseria gonorrhoeae and Chlamydia trachomatis. This metaanalysis identifies a considerable range of quality in study methods and research design and underscores the limitations inherent in comparing such data. Despite this, a number of antimicrobial regimens appear to have very good short-term clinical and microbiologic efficacy. Pooled clinical cure rates range from 75% to 94% and pooled microbiologic cure rates range from 71% to 100%. A cost comparison is provided, and future research priorities are suggested.

Comparison of rapid tests for detection of group B streptococcal colonization.

Accurate rapid detection of maternal lower genital tract colonization with group B streptococci (GBS) in high-risk patients is essential for selective institution of intrapartum antibiotic treatment to reduce neonatal GBS infection. In this study, pure GBS isolates were used to evaluate five commercially available rapid tests in terms of speed, ease of use, and sensitivity. The products tested were Directigen, Equate, Bactigen, PathoDx, and Phadebact. Although each test could be performed relatively quickly, the ease of performance and level of sensitivity (10(5) to 10(8) CFU/ml) varied markedly. Quantitative cultures obtained from 17 known GBS carriers showed concentrations ranging from less than 10(2) to greater than 10(8) CFU/gm of vaginal material. Since only 40% of the women had greater than or equal to 10(5) CFU/gm of vaginal material, it appears that many colonized women would not be identified by these rapid tests.

Pelvic inflammatory disease. Key treatment issues and options.

OBJECTIVE: --To examine available data regarding optimal antimicrobial therapy for pelvic inflammatory disease (PID) and to address selected treatment issues confronting clinicians caring for women with PID. DATA SOURCES: --Studies evaluated to help establish the Centers for Disease Control's 1989 Sexually Transmitted Diseases Treatment Guidelines and other reports published since 1985. A MEDLINE search of English-language literature was conducted using the indexing terms "pelvic inflammatory disease" or "pelvic infections" or "salpingitis" and "treatment". In addition, abstracts and bibliographies of articles and books were reviewed. STUDY SELECTION: --Studies were selected for detailed review if they evaluated the effectiveness of an antimicrobial regimen for treatment of PID. DATA EXTRACTION: --All studies were evaluated to determine the numbers of women treated and the percentage with clinical or microbiologic evidence of cure. DATA SYNTHESIS: --A variety of combination antimicrobial regimens are highly effective in providing clinical and microbiologic evidence of cure; few data are available to assess optimal therapy for prevention of late sequelae. Because PID is polymicrobial in cause, recommended antimicrobial regimens are broad-spectrum in coverage. CONCLUSIONS: --No single agent that provides sufficient coverage is currently available. Several combination regimens appear highly effective clinically even among women with tubo-ovarian abscess formation. Uncertainties regarding the effectiveness of antimicrobial therapy for prevention of late sequelae complicate decisions regarding the choice among regimens and the appropriateness of ambulatory treatment of women with PID. Pending better data, hospitalization should be strongly considered, where feasible, particularly for those women with PID desiring further childbearing. Sex partners of all women with PID should be treated.

Diagnosing pelvic inflammatory disease. A comprehensive analysis and considerations for developing a new model.

OBJECTIVE: --To examine the accuracy of existing diagnostic indicators for pelvic inflammatory disease and to develop guidelines for a new diagnostic model. DATA SOURCES: --Studies were identified for the period 1969 through 1990. A Medline search of the English-language literature was conducted using the subject terms pelvic inflammatory disease or salpingitis and diagnosis. In addition, abstracts and bibliographies of articles and books were reviewed. STUDY SELECTION: --Studies were selected if pelvic inflammatory disease was diagnosed using laparoscopic findings or narrow clinical rules. Of the 15 reports identified, 12 were included in this analysis. The selected studies were grouped by a quality rating based on subject selection, definition of pelvic inflammatory disease, data analysis, and other measures. DATA EXTRACTION: --Diagnostic findings were divided into four categories: historical (symptoms), clinical examination (signs), laboratory, and combinations of the above. Sensitivity and specificity were extracted using raw data. Data were classified by quality rating. DATA SYNTHESIS: --Historical findings were usually not statistically significant predictors of pelvic inflammatory disease, and when they were they tended toward low sensitivity and high specificity, while clinical findings were somewhat more sensitive and about as specific. Several laboratory tests showed consistent value in pelvic inflammatory disease diagnosis, with high sensitivity and specificity. Combinations of indicators permitted high sensitivity or high specificity but not both simultaneously. CONCLUSIONS: --No single or combination diagnostic indicator was found to reliably predict pelvic inflammatory disease. Combining published evidence with practical clinical considerations, a diagnostic approach is proposed that emphasizes diagnostic sensitivity when clinical presentation is mild and more thorough evaluation when a woman is severely ill. Research is needed to evaluate the accuracy and acceptability of specific diagnostic models and to investigate new diagnostic indicators.

Anti-infective drugs in obstetrics and gynecology.

Prophylactic and therapeutic options for reproductive infections are continually shifting. In this review, highlights from the recent literature of anti-infective drugs in obstetrics and gynecology are presented. Several articles offer new insights into the basic pathophysiology of common infections. Others provide novel strategies in prophylaxis for women with recurrent infections and for those undergoing surgical procedures. In the therapy arena, refinements in dosing schedules favor lower doses and shorter courses for some infections. Intriguing data regarding infrequently discussed infectious processes are presented. Finally, as new, more sophisticated agents flood the market, they are compared against the gold standards of treatment.

Stressed to kill.

Many employees are suffering burnout due to work and family-related stress. What are the effects of stress in the workplace? And what can employers do to check the effects of this unseen, but dangerous, enemy?

Comparison of cefotetan plus doxycycline with cefoxitin plus doxycycline in the inpatient treatment of acute salpingitis.

Pelvic inflammatory disease (PID), one of the major sequelae of the current epidemic of sexually transmitted diseases, has been shown to be a polymicrobial infection. This study compares the efficacy and safety of two broad-spectrum combination drug regimens, cefotetan with doxycycline and cefoxitin with doxycycline, in the treatment of PID. A total of 108 patients with acute salpingitis were hospitalized and randomized into two treatment groups: cefotetan/doxycycline (N = 54) and cefoxitin/doxycycline (N = 54). Before antibiotic administration, Chlamydia trachomatis was identified in 17 (16%) of the patients, Neisseria gonorrhoeae from 72 (67%), and anaerobic and aerobic bacteria were identified from the endometrial cultures of 86 (80%). There were seven tubo-ovarian abscesses (TOAs) that were diagnosed in the cefotetan group, and six in the cefoxitin group. Clinical cure was achieved in 51 of 54 (94%) patients in each group. Of the six patients whose treatment failed, all had positive cultures for N. gonorrhoeae and facultative/anaerobic bacteria, whereas none had C. trachomatis. Two patients from each study arm whose treatment failed were diagnosed with TOAs and responded subsequently to clindamycin plus an aminoglycoside. Cultures that were obtained after the completion of inpatient treatment showed the eradication of C. trachomatis and N. gonorrhoeae in all patients. Also, both regimens were effective in reducing aerobic and anaerobic pathogens. Finally, both regimens were well tolerated, with few side-effects.