Catamenial epilepsy occurrence and patterns in a mixed population of women with epilepsy.

We evaluated the occurrence and distribution of patterns of catamenial epilepsy in a heterogenous cohort of women with epilepsy on no hormonal therapies, enrolled in a prospective, observational study. The primary aim of the study was pregnancy rate in women with epilepsy with no prior reproductive problems. In this analysis, we included women who recorded one or more menstrual cycles with one or more seizures. We measured progesterone concentrations for one to three cycles. We defined catamenial patterns as twofold or greater average daily seizure frequency around menstruation (C1), ovulation (C2), and for anovulatory cycles, from midcycle through menstruation (C3). Twenty-three of the 89 enrolled women with epilepsy were eligible for this analysis; 12 of 23 met criteria for catamenial epilepsy; five of 23 demonstrated only a C1 pattern, two of 23 only a C2 pattern, five of 23 a combined C1/C2 pattern, and the one woman with anovulatory cycles did not demonstrate a C3 pattern. There were no differences in likelihood of demonstrating a catamenial pattern between those who reported a prior catamenial pattern and those who did not (p = .855). This analysis demonstrates the utility of app-based tracking to determine a catamenial pattern. Larger prospective studies could confirm these findings and inform potential therapeutic trial designs for catamenial epilepsy.

Maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation.

BACKGROUND: After preterm premature rupture of membranes at <24 weeks' gestation, pregnant women may choose continuation (expectant management) or termination of pregnancy, via either dilation and evacuation or labor induction. Neonatal outcomes after expectant management are well described. In contrast, limited research addresses maternal outcomes associated with expectant management compared to termination of pregnancy. OBJECTIVE: This study aimed to compare maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation in women who choose either expectant management or termination of pregnancy. STUDY DESIGN: This retrospective cohort study included women with preterm premature rupture of membranes between 14 0/7 and 23 6/7 weeks' gestation with singleton or twin pregnancies at 3 institutions from 2011 to 2018. We excluded pregnancies complicated by fetal anomalies, rupture of membranes immediately after obstetrical procedures (chorionic villus sampling, amniocentesis, cerclage placement, fetal reduction), spontaneous delivery <24 hours after membrane rupture, and contraindications to expectant management. Our primary outcome was the difference in composite maternal morbidity between women choosing expectant management and women choosing termination of pregnancy. We defined composite maternal morbidity as at least 1 of the following: chorioamnionitis, endometritis, sepsis, unplanned operative procedure after delivery (dilation and curettage, laparoscopy, or laparotomy), injury requiring repair, unplanned hysterectomy, unplanned hysterotomy (excluding cesarean delivery), uterine rupture, hemorrhage of >1000 mL, transfusion, admission to the maternal intensive care unit, acute renal insufficiency, venous thromboembolism, pulmonary embolism, and readmission to the hospital within 6 weeks. We compared the demographic and antenatal characteristics of women choosing expectant management with that of women choosing termination of pregnancy and used logistic regression to quantify the association between initial management decision and composite maternal morbidity. RESULTS: We identified 350 women with pregnancies complicated by preterm premature rupture of membranes at <24 weeks' gestation, and 208 women were eligible for the study. Of the 208 women, 108 (51.9%) chose expectant management as initial management, and 100 (48.1%) chose termination of pregnancy as initial management. Among women selecting termination of pregnancy, 67.0% underwent labor induction, and 33.0% underwent dilation and evacuation. Compared to women who chose termination of pregnancy, women who chose expectant management had 4.1 times the odds of developing chorioamnionitis (38.0% vs 13.0%; 95% confidence interval, 2.03-8.26) and 2.44 times the odds of postpartum hemorrhage (23.1% vs 11.0%; 95% confidence interval, 1.13-5.26). Admissions to the intensive care unit and unplanned hysterectomy only occurred after expectant management (2.8% vs 0.0% and 0.9% vs 0.0%). Of women who chose expectant management, 36.2% delivered via cesarean delivery with 56.4% non-low transverse uterine incisions. Composite maternal morbidity rates were 60.2% in the expectant management group and 33.0% in the termination of pregnancy group. After adjusting for gestational age at rupture, site, race and ethnicity, gestational age at entry to prenatal care, preterm premature rupture of membranes in a previous pregnancy, twin pregnancy, smoking, cerclage, and cervical examination at the time of presentation, expectant management was associated with 3.47 times the odds of composite maternal morbidity (95% confidence interval, 1.52-7.93), corresponding to an adjusted relative risk of 1.91 (95% confidence interval, 1.35-2.73). Among women who chose expectant management, 15.7% avoided morbidity and had a neonate who survived to discharge. CONCLUSION: Expectant management for preterm premature rupture of membranes at <24 weeks' gestation was associated with a significantly increased risk of maternal morbidity when compared to termination of pregnancy.

Female permanent contraception trends and updates.

Permanent contraception remains one of the most popular methods of contraception worldwide. This article has reviewed recent literature related to demographic characteristics of users, prevalence of use and trends over time, surgical techniques, and barriers to obtain the procedure. We have emphasized the patient's perspective as a key element of choosing permanent contraception. This review has incorporated sections on salpingectomy, hysteroscopy, unmet need, impact of policies at religiously affiliated institutions, and reproductive coercion.

Preferences and experiences of women with epilepsy regarding sexual and reproductive healthcare provision.

RATIONALE: Women with epilepsy (WWE) have unique disease-specific considerations regarding their sexual and reproductive health (SRH), which impact decision-making around pregnancy and contraception. Understanding their perspectives, preferences, and experiences regarding SRH care contributes to optimizing patient-centered clinical practice. METHODS: We conducted individual semi-structured interviews with WWE aged 18-45 years, exploring their SRH care experiences and preferences. We audio-recorded and transcribed all interviews. Two coders used both inductive and deductive strategies to perform thematic analysis and identify key themes and representative quotes. RESULTS: Twenty WWE completed interviews (median age 23 years; range 18-43 years). Key themes included: 1) SRH counseling from neurologists often did not occur, was limited in scope, or contained misinformation, especially during adolescence and early adulthood. In particular, participants felt that they received poor counseling about contraception, fertility, folic acid, and teratogenic medications, which impacted their reproductive decision-making. 2) WWE report fragmented care between their neurologist and other SRH providers. 3) WWE prefer that their neurologists initiate routine comprehensive discussions about SRH. 4) Conversations about SRH should begin in adolescence and include private confidential discussions between neurologists and WWE. 5) Successful SRH conversations between neurologists and WWE involve detailed information, reassurance, and support for the patient's reproductive goals. CONCLUSION: WWE desire comprehensive, coordinated counseling and care regarding SRH and epilepsy, and often experience suboptimal SRH care. Better understanding of the SRH needs, preferences, and experiences of WWE will help inform interventions to optimize patient-centered SRH counseling and care by healthcare professionals, especially during adolescence.

A baseline patch test series for New Zealand.

BACKGROUND: Patch testing is the gold standard diagnostic test for allergic contact dermatitis and needs to be relevant to the region and the population being tested. The aim of this study was to develop a specific New Zealand baseline series (NZBS). METHOD: We performed a retrospective case note review of patients attending four regional patch test centres between 2008 and 2020. Demographic and diagnostic information was collected for each patient along with results of patch testing. Using the results of this review, a group of 11 dermatologists with an interest in contact dermatitis agreed on a core group of allergens for inclusion in an NZBS, based on the frequency of positive reactions and allergens of interest. The remaining potential allergens were ranked by each dermatologist using an online questionnaire, with inclusion in the final NZBS by consensus. RESULTS: Results from 2402 patients (67% female, mean age 44 years) from Auckland, Wellington, Palmerston North and Christchurch were collated. The 10 most frequent positive (relevant and non-relevant) allergens were nickel sulfate (22.0%), fragrance mix I (8.6%), cobalt chloride (7.3%), Myroxylon pereirae (5.6%), colophonium (5.1%), p-phenylenediamine (4.9%), methylisothiazolinone/methylchloroisothiazolinone (4.1%), fragrance mix II (3.9%), potassium dichromate (3.5%) and methylisothiazolinone (3.4%). Based on these results, a core series of 30 allergens was developed, with an additional 30 allergens added to form the extended series (total 60 allergens). CONCLUSION: The baseline series of patch test allergens for routine use in New Zealand (NZBS) is based on national patch test data and expert consensus.

Constraints on Holographic Multifield Inflation and Models Based on the Hamilton-Jacobi Formalism.

In holographic inflation, the 4D cosmological dynamics is postulated to be dual to the renormalization group flow of a 3D Euclidean conformal field theory with marginally relevant operators. The scalar potential of the 4D theory-in which inflation is realized-is highly constrained, with use of the Hamilton-Jacobi equations. In multifield holographic realizations of inflation, fields additional to the inflaton cannot display underdamped oscillations (that is, their wave functions contain no oscillatory phases independent of the momenta). We show that this result is exact, independent of the number of fields, the field space geometry, and the shape of the inflationary trajectory followed in multifield space. In the specific case where the multifield trajectory is a straight line or confined to a plane, it can be understood as the existence of an upper bound on the dynamical masses m of extra fields of the form m≤3H/2 up to slow roll corrections. This bound corresponds to the analytic continuation of the well-known Breitenlohner-Freedman bound found in anti-de Sitter spacetimes in the case when the masses are approximately constant. The absence of underdamped oscillations implies that a detection of "cosmological collider" oscillatory patterns in the non-Gaussian bispectrum would not only rule out single-field inflation, but also holographic inflation or any inflationary model based on the Hamilton-Jacobi equations. Hence, future observations have the potential to exclude, at once, an entire class of inflationary theories, regardless of the details involved in their model building.

SMFM Special Report: Putting the "M" back in MFM: Addressing education about disparities in maternal outcomes and care.

At the 36th Annual meeting of the Society for Maternal-Fetal Medicine (SMFM), leaders in the field of maternal-fetal medicine (MFM) convened to address maternal outcome and care inequities from 3 perspectives: (1) education, (2) clinical care, and (3) research. Meeting attendees identified knowledge gaps regarding disparities within the provider community; reviewed possible frameworks to address these knowledge gaps; and identified models with which to address key clinical issues. Collaboration and communication between all stakeholders will be needed to gain a better understanding of these prevailing disparities and formulate strategies to eliminate them.

Uterine Transplantation: Surgical Innovation in the Treatment of Uterine Factor Infertility.

Uterine factor infertility (UFI) is a condition that affects thousands of women and is estimated to have a prevalence as high as one in five hundred reproductive-aged women. A wide range of circumstances can lead to UFI and include women with congenital absence of a uterus (Mayer Rokitansky Kuster Hauser or MRKH syndrome), women who have undergone iatrogenic removal of the uterus, or women who have uteri that are in situ but have been damaged by infection or surgical instrumentation. There have been 17 published reports of human uterine transplantation in the world. This article will summarize the history of human uterine transplantation and discuss our current understanding of the medical, surgical, and ethical considerations surrounding this innovative procedure.

Late-summer Disease Symptoms in Western Washington Red Raspberry Fields Associated with Co-Occurrence of Phytophthora rubi, Verticillium dahliae, and Pratylenchus penetrans, but not Raspberry bushy dwarf virus.

Sixty percent of the $109 million processed red raspberry industry of the United States occurs in northern Washington State. In 2012, late-summer symptoms of vascular wilt and root disease were observed in many raspberry plantings. These symptoms were initially attributed to Verticillium dahliae. However, diagnostic tests for the pathogen were often contradictory and other soilborne pathogens (Phytophthora rubi and Pratylenchus penetrans) or Raspberry bushy dwarf virus (RBDV) might also have been involved. Therefore, a survey was conducted in 2013 and 2014 to (i) establish the incidence and soil population levels of V. dahliae in red raspberry production fields, (ii) compare among diagnostic methods and laboratories for detecting and quantifying V. dahliae from raspberry field soil, and (iii) assess which pathogens are associated with late-summer disease symptoms of raspberry. Plant and soil samples were collected from 51 disease sites and 20 healthy sites located in 24 production fields. Samples were analyzed for the presence and quantity of each pathogen using traditional plating and extraction methods (V. dahliae, P. rubi, and P. penetrans), quantitative polymerase chain reaction (qPCR) (V. dahliae and P. rubi), and enzyme-linked immunosorbent assay (RBDV). Results showed that V. dahliae was present in 88% of the production fields and that detection of the pathogen differed by method and by laboratory: qPCR detected V. dahliae in the soil from approximately three times as many sites (51 of 71 total sites) as by plating on NP10 semi-selective medium (15 of 71 total sites). Soil populations of V. dahliae were slightly greater at disease sites, but the pathogen was detected with similar frequency from healthy sites and it was rarely isolated from diseased plants (4%). P. rubi, P. penetrans, and RBDV were also common in production fields (79, 91, and 53% of fields, respectively). Both P. rubi (soil and root samples) and P. penetrans (root populations only), but not RBDV, were more frequently found at disease sites than healthy sites, and the amount of P. rubi detected by qPCR was greater from disease sites than healthy sites. In addition, P. rubi was isolated from 27% of the symptomatic plants located at disease sites. Regardless of detection method, V. dahliae, P. rubi, and P. penetrans, either with or without RBDV, were more likely to co-occur at disease sites (73%) than healthy sites (35%), suggesting that a soilborne disease complex is present in raspberry production fields. Results indicate that P. rubi is the primary pathogen most strongly associated with late-summer symptoms of disease, but root populations of P. penetrans and higher soil populations of V. dahliae may also be of concern. Therefore, disease control methods should focus on all three soilborne pathogens.

Evaluating the role of Pleistocene refugia, rivers and environmental variation in the diversification of central African duikers (genera Cephalophus and Philantomba).

BACKGROUND: This study aims to assess the role that Pleistocene refugia, rivers and local habitat conditions may have played in the evolutionary diversification of three central African duiker species (Cephalophus dorsalis, C. callipygus and Philantomba monticola). Genetic data from geo-referenced feces were collected from a wide range of sites across Central Africa. Historical patterns of population genetic structure were assessed using a ~ 650 bp fragment of the mitochondrial control region and contemporary patterns of genetic differentiation were evaluated using 12 polymorphic microsatellite loci. RESULTS: Mitochondrial analyses revealed that populations of C. callipygus and P. monticola in the Gulf of Guinea refugium are distinct from other populations in west central Africa. All three species exhibit signatures of past population expansion across much of the study area consistent with a history of postglacial expansion. There was no strong evidence for a riverine barrier effect in any of the three species, suggesting that duikers can readily cross major rivers. Generalized dissimilarity models (GDM) showed that environmental variation explains most of the nuclear genetic differentiation in both C. callipygus and P. monticola. The forest-savanna transition across central Cameroon and the Plateaux Batéké region in southeastern Gabon show the highest environmentally-associated turnover in genetic variability. A pattern of genetic differentiation was also evident between the coast and forest interior that may reflect differences in precipitation and/or vegetation. CONCLUSIONS: Findings from this study highlight the historical impact of Pleistocene fragmentation and current influence of environmental variation on genetic structure in duikers. Conservation efforts should therefore target areas that harbor as much environmentally-associated genetic variation as possible in order to maximize species' capacity to adapt to environmental change.

Reasons for discontinuation of reversible contraceptive methods by women with epilepsy.

OBJECTIVE: To report the reasons for discontinuation of contraceptive methods by women with epilepsy (WWE). METHODS: These retrospective data come from a web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We determined the frequencies of contraceptive discontinuations and the reasons for discontinuation. We compared risk ratios for rates of discontinuation among contraceptive methods and categories. We used chi-square analysis to test the independence of discontinuation reasons among the various contraceptive methods and categories and when stratified by antiepileptic drug (AED) categories. RESULTS: Nine hundred fifty-nine of 2,393 (40.6%) individual, reversible contraceptive methods were discontinued. One-half (51.8%) of the WWE who discontinued a method discontinued at least two methods. Hormonal contraception was discontinued most often (553/1,091, 50.7%) with a risk ratio of 1.94 (1.54-2.45, p < 0.0001) compared to intrauterine devices (IUDs), the category that was discontinued the least (57/227, 25.1%). Among all individual methods, the contraceptive patch was stopped most often (79.7%) and the progestin-IUD was stopped the least (20.1%). The top three reasons for discontinuation among all methods were reliability concerns (13.9%), menstrual problems (13.5%), and increased seizures (8.6%). There were significant differences among discontinuation rates and reasons when stratified by AED category for hormonal contraception but not for any other contraceptive category. SIGNIFICANCE: Contraception counseling for WWE should consider the special experience profiles that are unique to this special population on systemic hormonal contraception.

Trends in gestational age at time of surgical abortion for fetal aneuploidy and structural abnormalities.

BACKGROUND: Screening for fetal aneuploidy has evolved over the past 2 decades. Whether these advances impact gestational age at abortion has received little study. OBJECTIVE: We sought to describe trends in the gestational age at the time of abortion by fetal diagnosis over an 11-year study period. We hypothesized that gestational age at time of abortion would decrease for fetal aneuploidy but remain unchanged for structural abnormalities. STUDY DESIGN: We conducted a retrospective case series of all women undergoing surgical abortion for fetal aneuploidy or structural abnormalities up to 24 weeks' gestation from 2004 through 2014 in a hospital operating room setting at a single, urban medical center. We excluded labor induction abortions (<1% of abortions at our medical center) and suction aspirations performed in the office practice. We performed suction aspiration up to 14 weeks and dilation and evacuation after that gestational age. We describe the median gestational age at abortion by fetal indication and year. RESULTS: For women undergoing abortion for fetal aneuploidy (n = 392), the median gestational age at time of abortion decreased from 19.0 weeks (interquartile range 18.0-21.0) in 2004 to 14.0 weeks (interquartile range 13.0-17.0) in 2014 (Kruskal-Wallis P < .0001). For women undergoing abortion for fetal structural abnormalities (n = 586), the median gestational age was ≥20 weeks for each year during the study interval (P = .1). As gestational age decreased in the fetal aneuploidy group, fewer women underwent dilation and evacuation and more became eligible for suction aspiration (<14 weeks). In 2004, >90% of women underwent dilation and evacuation for either indication. By 2014, 31% of women with fetal aneuploidy were eligible for suction aspiration compared to 11% of those with structural anomalies. CONCLUSION: Gestational age at the time of abortion for fetal aneuploidy decreased substantially from 2004 through 2014; earlier abortion is safer for women. In contrast, women seeking abortion for fetal structural abnormalities did not experience a change in timing. Legislation restricting gestational age at the time of abortion could disproportionately affect women with fetal structural abnormalities.

Folic acid use by women with epilepsy: Findings of the Epilepsy Birth Control Registry.

PURPOSE: To determine the prevalence and predictors of folic acid (FA) use by women with epilepsy (WWE) at risk of unintended pregnancy. METHODS: These retrospective data come from the Epilepsy Birth Control Registry (EBCR) web-based survey of 1144 WWE in the community, 18-47years, who provided demographic, epilepsy, AED, contraception, pregnancy, healthcare visits and FA data. We report prevalence and predictors of FA use in relation to risk of pregnancy (not at risk, at risk, seeking pregnancy, pregnant), demographics, seizure types and AED and contraception categories. RESULTS: 368 (47.6%) of the 773 WWE at risk of unintended pregnancy in the EBCR took FA supplement. Being at risk was a significant predictor in comparison to WWE not at risk (OR=1.464 [1.103-1.944], p=0.008). In comparison to WWE at risk, FA use trended greater for WWE actively seeking pregnancy (29/47, 61.7% v 368/773, 47.6%; p=0.0605) and was greater for pregnant WWE (17/19, 89.5% v 368/773, 47.6%; p=0.0007). Demographic predictors for WWE at risk were race (p=0.003), education (p=0.012) and income (0.043) with significantly greater FA use by Caucasians than minorities and direct correlations between FA use and levels of education and household income. Seizure type, AED use, category and dosage, polytherapy and contraceptive category were not predictors. A healthcare provider visit during the year prior to the survey was not a predictor. Prevalence of FA use was similar following visits with gynecologists - 51.7%, neurologists - 48.7% and primary care - 48.6%. FA supplementation by prescription was greater for WWE at risk on AED versus no AED (190/355, 53.5% v 3/13, 23.1%; p=0.045). CONCLUSION: Low prevalence of preconception FA use may reflect a need for more education. In addition, further research is needed to provide definitive evidence that FA reduces congenital malformations in the offspring of WWE.

Women with epilepsy initiating a progestin IUD: A prospective pilot study of safety and acceptability.

OBJECTIVE: Effective contraception enables women with epilepsy (WWE) to plan their pregnancies and improve outcomes for themselves and their children. Although popular among all women, complex drug interactions limit the efficacy and safety of oral contraceptives (OCs) for WWE. We sought to explore the safety, acceptability, and pharmacokinetic impact of a progestin-containing intrauterine device (IUD) in WWE. METHODS: We enrolled 20 women with well-controlled epilepsy and a stable antiepileptic drug (AED) regimen and who were initiating a progestin-containing IUD (levonorgestrel 52 mg) in a prospective, observational study. For each AED, we compared the trough concentration before IUD insertion to the trough concentration 3 weeks, and 3 and 6 months later. Participants recorded seizures in a daily paper diary. We compared seizures that occurred during the month before IUD insertion to those occurring in the 6 months thereafter. Participants completed an acceptability questionnaire at 3 and 6 months. RESULTS: Participants' average age was 28 years; 60% were nulligravid. They reported a history of multiple seizure types. During the baseline month, 75% were seizure-free and the remainder reported between one and three seizures. Fourteen received monotherapy and six received polytherapy. Lamotrigine use was most common (n = 12). AED trough concentrations remained stable during the 6 months after IUD insertion, without clinically meaningful deviations from baseline. Diary data showed that seizure frequency worsened in 3, and remained unchanged in 13 and improved in 4 after IUD insertion. Subjectively, no participant believed the IUD worsened her seizure control. All participants were either somewhat or very satisfied with the IUD throughout the study. All participants continued the IUD use at 6 months. No pregnancies occurred. SIGNIFICANCE: This pilot study suggests that the progestin-containing IUD is a safe and acceptable long-acting contraceptive for WWE.

Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry.

OBJECTIVE: To report the contraceptive practices of women with epilepsy (WWE) in the community, predictors of highly effective contraception use, and reasons WWE provide for the selection of a particular method. METHODS: These cross-sectional data come from the Epilepsy Birth Control Registry (EBCR) web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We report demographic, epilepsy, and antiepileptic drug (AED) characteristics as well as contraceptive use. We determined the frequency of use of highly effective contraception use, that is, methods with failure rate <10%/year, and conducted binary logistic regression analysis to determine predictors of highly effective contraception use. We report frequencies of WWE who consult various health care providers regarding the selection of a method and the reasons cited for selection. RESULTS: Of the 796 WWE at risk of unintended pregnancy, 69.7% use what is generally considered to be highly effective contraception (hormonal, intrauterine device [IUD], tubal, vasectomy). Efficacy in WWE, especially for the 46.6% who use hormonal contraception, remains to be proven. Significant predictors of highly effective contraception use are insurance (insured 71.6% vs. noninsured 56.0%), race/ethnicity (Caucasian 71.3% vs. minority 51.0%), and age (38-47, 77.5%; 28-37, 71.8%; 18-27, 67.0%). Of the 87.2% who have a neurologist, only 25.4% consult them regarding selection of a method, although AED interaction is cited as the top reason for selection. SIGNIFICANCE: The EBCR web-based survey is the first large-scale study of the contraceptive practices of WWE in the community. The findings suggest a need for the development of evidence-based guidelines that address the efficacy and safety of contraceptive methods in this special population, and for greater discourse between neurologists and WWE regarding contraception.

Patient advocacy: Japanese psychiatric nurses recognizing necessity for intervention.

BACKGROUND: Advocacy is an important role of psychiatric nurses because their patients are ethically, socially, and legally vulnerable. This study of Japanese expert psychiatric nurses' judgments of interventions for patient advocacy will show effective strategies for ethical nursing practice and their relationship with Japanese culture. OBJECTIVES: This article explores Japanese psychiatric nurses' decision to intervene as a patient advocate and examine their ethical, cultural, and social implications. RESEARCH DESIGN: Using semi-structured interviews verbatim, themes of the problems that required interventions were inductively summarized by a qualitative analysis and their contexts and nursing judgments were examined. PARTICIPANTS AND RESEARCH CONTEXT: The participants were 21 nurses with 5 or more years of experience in psychiatric nursing. ETHICAL CONSIDERATIONS: The research was approved by Institutional Review Board of research site and study facilities. The participants gave written informed consent. FINDINGS: Analysis of 45 cases showed that nurses decided to intervene when (a) surrounding people's opinions impeded patients' safety, (b) healthcare professionals' policies impeded patients' decision-making, (c) own violent behaviors impeded treatment and welfare services for patients, (d) own or families' low acceptance of illness impeded patients' self-actualization, (e) inappropriate treatment or care impeded patients' liberty, and (f) their families abused patients' property. DISCUSSION: To solve conflicts between patients and their surrounding people, the nurses sought reconciliation between them, which is in accordance with Japanese cultural norms respecting harmony. When necessary, however, they protected patients' rights against cultural norms. Therefore, their judgments cannot be explained by cultural norms alone. CONCLUSION: The findings indicate that the nurses' judgments were based on respect for patients' rights apart from cultural norms, and they first sought solutions fitting the cultural norms before other solutions. This seems to be an ethical, effective strategy if advocates know the culture in depth.

Accelerated high-yield generation of limb-innervating motor neurons from human stem cells.

Human pluripotent stem cells are a promising source of differentiated cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that within 3 weeks induce motor neurons at up to 50% abundance and with defined subtype identities of relevance to neurodegenerative disease. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1, and column-specific markers that mirror those observed in vivo in human embryonic spinal cord. They also exhibited spontaneous and induced activity, and projected axons toward muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1(+)/LHX3(-)). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays.

Landscape effects on gene flow for a climate-sensitive montane species, the American pika.

Climate change is arguably the greatest challenge to conservation of our time. Most vulnerability assessments rely on past and current species distributions to predict future persistence but ignore species' abilities to disperse through landscapes, which may be particularly important in fragmented habitats and crucial for long-term persistence in changing environments. Landscape genetic approaches explore the interactions between landscape features and gene flow and can clarify how organisms move among suitable habitats, but have suffered from methodological uncertainties. We used a landscape genetic approach to determine how landscape and climate-related features influence gene flow for American pikas (Ochotona princeps) in Crater Lake National Park. Pikas are heat intolerant and restricted to cool microclimates; thus, range contractions have been predicted as climate changes. We evaluated the correlation between landscape variables and genetic distance using partial Mantel tests in a causal modelling framework, and used spatially explicit simulations to evaluate methods of model optimization including a novel approach based on relative support and reciprocal causal modelling. We found that gene flow was primarily restricted by topographic relief, water and west-facing aspects, suggesting that physical restrictions related to small body size and mode of locomotion, as well as exposure to relatively high temperatures, limit pika dispersal in this alpine habitat. Our model optimization successfully identified landscape features influencing resistance in the simulated data for this landscape, but underestimated the magnitude of resistance. This is the first landscape genetic study to address the fundamental question of what limits dispersal and gene flow in the American pika.

Quality control within the multicentre perfusion CT study of primary colorectal cancer (PROSPeCT): results of an iodine density phantom study.

OBJECTIVES: To assess the cross-centre consistency of iodine enhancement, contrast-to-noise ratio and radiation dose in a multicentre perfusion CT trial of colorectal cancer. MATERIALS AND METHODS: A cylindrical water phantom containing different iodine inserts was examined on seven CT models in 13 hospitals. The relationship between CT number (Hounsfield units, HU) and iodine concentration (milligrams per millilitre) was established and contrast-to-noise ratios (CNRs) calculated. Radiation doses (CTDIvol, DLP) were compared across all sites. RESULTS: There was a linear relationship between CT number and iodine density. Iodine enhancement varied by a factor of at most 1.10, and image noise by at most 1.5 across the study sites. At an iodine concentration of 1 mg ml(-1) and 100 kV, CNRs ranged from 3.6 to 4.8 in the 220-mm phantom and from 1.4 to 1.9 in the 300-mm phantom. Doses varied by a factor of at most 2.4, but remained within study dose constraints. Iterative reconstruction algorithms did not alter iodine enhancement but resulted in reduced image noise by a factor of at most 2.2, allowing a potential dose decrease of at most 80% compared to filtered back projection (FBP). CONCLUSIONS: Quality control of CT performance across centres indicates that CNR values remain relatively consistent across all sites, giving acceptable image quality within the agreed dose constraints. KEY POINTS: Quality control is essential in a multicentre setting to enable CT quantification. CNRs in a body-sized phantom had the recommended value of at least 1.5. CTDIs and DLPs varied by factors of 1.8 and 2.4 respectively.

Observational study of regional aortic size referenced to body size: production of a cardiovascular magnetic resonance nomogram.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is regarded as the gold standard for clinical assessment of the aorta, but normal dimensions are usually referenced to echocardiographic and computed tomography data and no large CMR normal reference range exists. As a result we aimed to 1) produce a normal CMR reference range of aortic diameters and 2) investigate the relationship between regional aortic size and body surface area (BSA) in a large group of healthy subjects with no vascular risk factors. METHODS: 447 subjects (208 male, aged 19-70 years) without identifiable cardiac risk factors (BMI range 15.7-52.6 kg/m2) underwent CMR at 1.5 T to determine aortic diameter at three levels: the ascending aorta (Ao) and proximal descending aorta (PDA) at the level of the pulmonary artery, and the abdominal aorta (DDA), at a level 12 cm distal to the PDA. In addition, 201 of these subjects had aortic root imaging, allowing for measurements at the level of the aortic valve annulus (AV), aortic sinuses and sinotubular junction (STJ). RESULTS: Normal diameters (mean ±2 SD) were; AV annulus male(♂) 24.4 ± 5.4, female (♀) 21.0 ± 3.6 mm, aortic sinus♂ 32.4 ± 7.7, ♀27.6 ± 5.8 mm, ST-junction ♂25.0 ± 7.4, ♀21.8 ± 5.4 mm, Ao ♂26.7 ± 7.7, ♀25.5 ± 7.4 mm, PDA ♂20.6 ± 5.6, +18.9 ± 4.0 mm, DDA ♂17.6 ± 5.1, ♀16.4 ± 4.0 mm. Aortic root and thoracic aortic diameters increased at all levels measured with BSA. No gender difference was seen in the degree of dilatation with increasing BSA (p>0.5 for all analyses). CONCLUSION: Across both genders, increasing body size is characterized by a modest degree of aortic dilatation, even in the absence of traditional cardiovascular risk factors.