Testing fixed points in the 2D O(3) non-linear sigma model

Using high statistic numerical results we investigate the properties of the O(3) non-linear 2D sigma-model. Our main concern is the detection of an hypothetical Kosterlitz-Thouless-like (KT) phase transition which would contradict the asymptotic freedom scenario. Our results do not support such a KT-like phase transition.Comment: Latex, 7 pgs, 4 eps-figures. Added more analysis on the KT-transition. 4-loop beta function contains corrections from D.-S.Shin (hep-lat/9810025). In a note-added we comment on the consequences of these corrections on our previous reference [16

Inclusion and diversity within medical education: a focus group study of students' experiences

Background/introduction As patient populations become more diverse, it is imperative that future physicians receive proper training in order to provide the best quality of care. This study examines medical students' perceptions of how prepared they are in dealing with a diverse population and assesses how included and supported the students felt during their studies. Methods Four semi-structured focus groups were held with medical students across all years of the medical study program of a Dutch university. Focus group transcripts were analyzed thematically. Results Students’ experiences could be categorized as follows: (1) (Minority) identities and personal motivations, (2) Understanding of diversity and an inclusive learning environment, (3) Diversity in education, (4) Experiences of exclusion, (5) Experiences of inclusion, and (6) Lack of awareness. The key findings from the focus groups were that students perceived a lack of diversity and awareness in medical education and were convinced of the need to incorporate diversity to a greater extent and were personally motivated to contribute to incorporating diversity in the curriculum. Students also shared exclusion experiences such as stereotypes and prejudices but also some inclusion experiences such as feelings of belonging. Conclusion Based on our findings, it is recommended that medical schools incorporate diversity education into their curriculum so that health professionals can provide the best quality of care for their diverse patient populations. This education should also ensure that all students feel included in their medical education program

Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant.

Biallelic mutations of the alsin Rho guanine nucleotide exchange factor (ALS2) gene cause a group of overlapping autosomal recessive neurodegenerative disorders including infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (JALS/ALS2), caused by retrograde degeneration of the upper motor neurons of the pyramidal tracts. Here, we describe 11 individuals with IAHSP, aged 2-48 years, with IAHSP from three unrelated consanguineous Iranian families carrying the homozygous c.1640+1G>A founder mutation in ALS2. Three affected siblings from one family exhibit generalized dystonia which has not been previously described in families with IAHSP and has only been reported in three unrelated consanguineous families with JALS/ALS2. We report the oldest individuals with IAHSP to date and provide evidence that these patients survive well into their late 40s with preserved cognition and normal eye movements. Our study delineates the phenotypic spectrum of IAHSP and ALS2-related disorders and provides valuable insights into the natural disease course

Breaking seed dormancy and micropropagation of perennial vulneraria milkvetch (Astragalus vulnerariae DC.)

In this study, an efficient system to break seed dormancy and plant regeneration was established for perennial vulneraria milkvetch (Astragalus vulnerariae DC.). The seed coat dormancy could be easily released using 40% sulphuric acid treatment for 15 minutes, which made the seed coat permeable without damaging zygotic embryos. The tissue culture studies reported regeneration on 5 explants, which had variable effects on shoot regeneration, using MS medium containing variable concentrations of Kin–NAA and BAP–NAA. Maximum shoot regeneration of 86.67% with 4.47 shoots per explant was noted on MS medium containing 0.5 mg·l–1 Kin – 0.5 mg·l–1 NAA on hypocotyl explants. No shoot regeneration was noted on cotyledon leaf and shoot nodes using MS medium containing any concentration of BAP–NAA. Maximum shoot regeneration of 50% with 3 shoots per explant was also observed on 1 mg·l–1 BAP – 0.5 mg·l–1 NAA on epicotyl explants. MS medium containing Kin–NAA induced hypocotyl explant shoots had rooting percentage of 36.67% on 0.5 mg·l–1 IBA, whereas, MS medium containing BAP–NAA induced hypocotyl shoots had rooting percentage of 46.67%. The in vitro cultured plants had an acclimatization rate of 78%. Aesthetically attractive, economical, easy to maintain and water efficient vulneraria milkvetch is currently not available in landscaping. The system of plant regeneration and adaptation suggested by this paper may help to dissipate it to a broad range of water scarce environments as a sustainable and inexpensive choice

The regulation and signalling of anti-Müllerian hormone in human granulosa cells: relevance to polycystic ovary syndrome.

STUDY QUESTION: What prevents the fall in anti-Müllerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and what are the consequences of this for follicle progression in these ovaries? SUMMARY ANSWER: Exposure of granulosa cells (GCs) to high levels of androgens, equivalent to that found in PCOS, prevented the fall in AMH and was associated with dysregulated AMH-SMAD signalling leading to stalled follicle progression in PCOS. WHAT IS KNOWN ALREADY: In normal ovaries, AMH exerts an inhibitory role on antral follicle development and a fall in AMH levels is a prerequisite for ovulation. Levels of AMH are high in PCOS, contributing to the dysregulated follicle growth that is a common cause of anovulatory infertility in these women. STUDY DESIGN, SIZE, DURATION: Human KGN-GC (the cell line that corresponds to immature GC from smaller antral follicles (AF)) were cultured with a range of doses of various androgens to determine the effects on AMH production. KGN-GC were also treated with PHTPP (an oestrogen receptor β (ERβ) antagonist) to examine the relationship between AMH expression and the ratio of ERα:ERβ. The differential dose-related effect of AMH on gene expression and SMAD signalling was investigated in human granulosa-luteal cells (hGLC) from women with normal ovaries, with polycystic ovarian morphology (PCOM) and with PCOS. KGN-GC were also cultured for a prolonged period with AMH at different doses to assess the effect on cell proliferation and viability. PARTICIPANTS/MATERIALS, SETTING, METHODS: AMH protein production by cells exposed to androgens was measured by ELISA. The effect of PHTPP on the mRNA expression levels of AMH, ERα and ERβ was assessed by real-time quantitative PCR (qPCR). The influence of AMH on the relative mRNA expression levels of aromatase, AMH and its receptor AMHRII, and the FSH and LH receptor (FSHR and LHR) in control, PCOM and PCOS hGLCs was quantified by qPCR. Western blotting was used to assess changes in levels of SMAD proteins (pSMAD-1/5/8; SMAD-4; SMAD-6 and SMAD-7) after exposure of hGLCs from healthy women and women with PCOS to AMH. The ApoTox-Glo Triplex assay was used to evaluate the effect of AMH on cell viability, cytotoxicity and apoptosis. MAIN RESULTS AND THE ROLE OF CHANCE: Testosterone reduced AMH protein secreted from KGN-GC at 10-9-10-7 M (P < 0.05; P < 0.005, multiple uncorrected comparisons Fishers least squares difference), but at equivalent hyperandrogenemic levels no change was seen in AMH levels. 5α-DHT produced a significant dose-related increase in AMH protein secreted into the media (P = 0.022, ANOVA). Increasing the mRNA ratio of ERα:ERβ produced a corresponding increase in AMH mRNA expression (P = 0.015, two-way ANOVA). AMH increased mRNA levels of aromatase (P < 0.05, one-way ANOVA) and FSHR (P < 0.0001, one-way ANOVA) in hGLCs from women with PCOM, but not from normal cells or PCOS (normal n = 7, PCOM n = 5, PCOS n = 4). In contrast to hGLCs from ovulatory ovaries, in PCOS AMH reduced protein levels (cell content) of stimulatory pSMAD-1/5/8 and SMAD-4 but increased inhibitory SMAD-6 and -7 (P < 0.05, normal n = 6, PCOS n = 3). AMH at 20 and 50 ng/ml decreased KGN-GC cell proliferation but not viability after 8 days of treatment (P < 0.005, two-way ANOVA). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Luteinised GC from women undergoing IVF have a relatively low expression of AMH/AMHRII but advantageously continue to display responses inherent to the ovarian morphology from which they are collected. To compensate, we also utilised the KGN cell line which has been characterised to be at a developmental stage close to that of immature GC. The lack of flutamide influence on testosterone effects is not in itself sufficient evidence to conclude that the effect on AMH is mediated via conversion to oestrogen, and the effect of aromatase inhibitors or oestrogen-specific inhibitors should be tested. The effect of flutamide was tested on testosterone but not DHT. WIDER IMPLICATIONS OF THE FINDINGS: Normal folliculogenesis and ovulation are dependent on the timely reduction in AMH production from GC at the time of follicle selection. Our findings reveal for the first time that theca-derived androgens may play a role in this model but that this inhibitory action is lost at levels of androgens equivalent to those seen in PCOS. The AMH decline may either be a direct effect of androgens or an indirect one via conversion to oestradiol and acting through the upregulation of ERα, which is known to stimulate the AMH promoter. Interestingly, the ability of GCs to respond to this continually elevated AMH level appears to be reduced in cells from women with PCOS due to an adaptive alteration in the SMAD signalling pathway and lower expression of AMHRII, indicating a form of 'AMH resistance'. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Thomas Addison Scholarship, St Georges Hospital Trust. The authors report no conflict of interest in this work and have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A