Isolated Ocular Relapse of Acute Myeloid Leukaemia Post Allogeneic Stem Cell Transplant.

We present a rare case of a 39-year-old female with extramedullary relapse of acute myeloid leukaemia (AML) isolated to the left eye 2 months post allogeneic haematopoietic stem cell transplant. She initially presented with painless left eye erythema, swelling, and visual impairment. Initial ophthalmology review revealed conjunctival chemosis, raised intraocular pressure, and serous retinal detachments. She was initially treated for suspected orbital cellulitis with intravenous antibiotic and antifungal therapy but clinically progressed so was then treated with intravenous corticosteroids. One week later, she progressed to angle-closure glaucoma with development of a hypopyon and an enlarging subconjunctival mass. She proceeded to urgent subconjunctival biopsy and drainage of subretinal fluid which confirmed extramedullary relapse of AML. Notably, further investigation found no evidence of bone marrow or central nervous system relapse. She proceeded to localized radiotherapy with gradual resolution of the subconjunctival mass and serous retinal detachment and was for consideration of donor lymphocyte infusions and azacitidine therapy; unfortunately, she developed respiratory sepsis and passed away despite maximal efforts. This case represents a rare and unusual presentation of isolated ocular extramedullary relapse of AML and emphasises the importance of early ophthalmology involvement and tissue biopsy when there is high clinical suspicion of the disease.

A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability.

It is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the tryptophan REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides, to multitryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibodies in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating biomolecular simulation with experimental data to yield novel insights.

Global parental leave in surgical careers: differences according to gender, geographical regions and surgical career stages.

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally. METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career. RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance. CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.

Factors associated with healing, reoperation and continence disturbance in patients following surgery for fistula-in-ano.

AIM: Fistula-in-ano (FIA) is associated with high treatment costs and has a deleterious impact on quality of life. A wide range of healing, incontinence and recurrence rates have been reported. This study aimed to identify operative, patient and disease factors that influence these outcomes after surgery for FIA. METHOD: An observational cohort study of consecutive patients who were managed for FIA at a tertiary colorectal practice (1999-2019) was performed. Outcome measures included healing, impaired continence and the need to reoperate. Clinico-pathological variables, including patient comorbidities, fistula anatomy and operative approach, were assessed for their association with these outcomes. RESULTS: Some 411 procedures were performed on 263 patients [median age 41.8 years (range 17.8-79.7 years), 184 men (70.0%)]. Some 77.9% of patients achieved complete healing, 9.5% experienced some deterioration in continence postoperatively and 37.6% required reoperation at a median time of 19.0 weeks. Poorer healing was associated with Crohn's disease, high trans-sphincteric fistulas, extrasphincteric fistulas and steroid usage. Poorer continence was associated with female sex, age > 40 years, posterior location, suprasphincteric fistulas, seton insertion and having more than three subsequent procedures. The need to reoperate was associated with female sex, high trans-sphincteric fistulas, suprasphincteric fistulas, inflammatory bowel disease and previous operations for FIA. CONCLUSION: Minimizing recurrence of FIA and preservation of continence can be competing management goals. More than one in three patients require reoperation, one in five fails to heal completely and one in ten suffers worsened continence following surgery. Awareness of the factors that contribute to these outcomes is important to the process of informed consent and managing patient expectations before surgery.

Elderly males with or without existing osteoporotic vertebral fracture have much lower future vertebral fracture risk than elderly females: the MrOS (Hong Kong) year-4 follow-up spine radiograph study.

MrOS (Hong Kong)'s year-4 follow-up shows, for subjects at baseline without vertebral deformity (VD) and endplate or/and cortex fracture (ECF), the VD progression/new VD rate during follow-up in males was half of our paired MsOS (Hong Kong) study's results. For those with VD or ECF, the VD progression/new VD was less than one sixth of females' rate. INTRODUCTION: This study documents MrOS (Hong Kong)'s year-4 follow-up, and the results are compared with the MsOS (Hong Kong) study. Of elderly females with Genant's grade-0, -1, -2, and -3 VD, at year-4 follow-up, 4.6%, 8%, 10.6%, and 28.9% had at least one VD progression or incident VD, respectively. METHODS: Spine radiographs of 1500 Chinese males with baseline (mean age 71.7 years, range 65-91 years) and year-4 follow-up were evaluated according to Genant's VD criteria and ECF (non-existent, ECF0; or existent, ECF1). Grade-2 VDs were divided into mild (VD2m, 25-34% height loss) and severe (VD2s, 34-40% height loss) subgroups. Study subjects were graded into eight categories: VD0/ECF0, VD1/ECF0, VD2m/ECF0, VD0/ECF1, VD1/ECF1, VD2m/ECF1, VD2s/ECF1, and VD3/ECF1. With an existing VD, a further height loss of ≥ 15% was a VD progression. A new VD incident was a change from grade-0 to grade-2/3, or to grade-1 with ≥ 10% height loss. RESULTS: Of subjects with Genant's grade-0, 2.05% (25/1219) developed at least one VD progression or/and new VD, while of subjects with Genant's grade-1, -2, and -3 VD, only 2% (3/149), 3.1% (3/96), and 2.8% (1/36) developed at least one VD progression/new VD, respectively. Among the three ECF0 groups, there was a significant difference in new ECF incidence, with VD0/ECF0 being the lowest and VD2m/ECF0 being the highest. CONCLUSION: VD progression/new VD is much less common in elderly men than in elderly women. Vertebrae with VD had a higher risk of developing ECF.

Osteoporotic vertebral deformity with endplate/cortex fracture is associated with higher further vertebral fracture risk: the Ms. OS (Hong Kong) study results.

Compared with vertebrae without deformity, vertebrae with mild/moderate deformity have a higher risk of endplate or/and cortex fracture (ecf). Compared with subjects without ecf, subjects with ecf are at a higher risk of short-term (4-year period) deformity progression and new incident deformity. INTRODUCTION: The progression and incidence of osteoporotic vertebral deformity/fracture (VD/VF) in elderly Chinese females remain not well documented. METHODS: Spine radiographs of 1533 Chinese females with baseline and year-4 follow-up (mean age 75.7 years) were evaluated according to Genant's VD criteria and endplate/cortex fracture (non-existent: ecf0 or existent: ecf1). Grade-2 VDs were divided into mild (vd2m, 25-34% height loss) and severe (vd2s, 34-40% height loss) subgroups. According to their VD/VF, subjects were graded into seven categories: vd0/ecf0, vd1/ecf0, vd2m/ecf0, vd1/ecf1, vd2m/ecf1, vd2s/ecf1, and vd3/ecf1. With an existing VD, a further height loss of ≥ 15% was a VD progression. A new incident VD was a change from grade-0 to grade-2/3 or to grade-1 with ≥ 10% height loss. RESULTS: Of subjects with Genant's grades 0, - 1, - 2, and - 3 VD, at follow-up, 4.6%, 8%, 10.6%, and 28.9% had at least one VD progression or new incident VD respectively. Among the three ecf0 groups, there was no difference in VD progression or new VD; while there was a significant difference in new ecf incidence, with vd0/ecf0 being lowest and vd2m/ecf0 being highest. Vd1/ecf0 and vd2m/ecf0 vertebrae had a higher risk of turning to ecf1 than vd0/ecf0 vertebrae. If vd1/ecf0 and vd2m/ecf0 subjects were combined together (range 20-34% height loss) to compare with vd1/ecf1 and vd2m/ecf1 subjects, the latter had significantly higher VD progression and new VD rates. CONCLUSION: Vertebrae with grade-1/2 VDs had a higher risk of developing ECF. Subjects with pre-existing ECFs had a higher risk of worsening or new vertebral deformities.

The first pilot study of expanded newborn screening for inborn errors of metabolism and survey of related knowledge and opinions of health care professionals in Hong Kong.

INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

Spaceflight-Relevant Challenges of Radiation and/or Reduced Weight Bearing Cause Arthritic Responses in Knee Articular Cartilage.

There is little known about the effect of both reduced weight bearing and exposure to radiation during spaceflight on the mechanically-sensitive cartilage lining the knee joint. In this study, we characterized cartilage damage in rat knees after periods of reduced weight bearing with/without exposure to solar-flare-relevant radiation, then cartilage recovery after return to weight bearing. Male Sprague Dawley rats (n = 120) were either hindlimb unloaded (HLU) via tail suspension or remained weight bearing in cages (GROUND). On day 5, half of the HLU and GROUND rats were 1 Gy total-body X-ray irradiated during HLU, and half were sham irradiated (SHAM), yielding 4 groups: GROUND-SHAM; GROUND-IR; HLU-SHAM; and HLU-IR. Hindlimbs were collected from half of each group of rats on day 13. The remaining rats were then removed from HLU or remained weight bearing, and hindlimbs from these rats were collected on day 62. On day 13, glycosaminoglycan (GAG) content in cartilage lining the tibial plateau and femoral condyles of HLU rats was lower than that of the GROUND animals. Likewise, on day 13, immunoreactivity of the collagen type II-degrading matrix metalloproteinase-13 (MMP-13) and of a resultant metalloproteinase-generated neoepitope VDIPEN was increased in all groups versus GROUND-SHAM. Clustering of chondrocytes indicating cartilage damage was present in all HLU and IR groups versus GROUND-SHAM on day 13. On day 62, after 49 days of reloading, the loss of GAG content was attenuated in the HLU-SHAM and HLU-IR groups, and the increased VDIPEN staining in all treatment groups was attenuated. However, the increased chondrocyte clustering remained in all treatment groups on day 62. MMP-13 activity also remained elevated in the GROUND-IR and HLU-IR groups. Increased T2 relaxation times, measured on day 62 using 7T MRI, were greater in GROUND-IR and HLU-IR knees, indicating persistent cartilage damage in the irradiated groups. Both HLU and total-body irradiation resulted in acute degenerative and pre-arthritic changes in the knee articular cartilage of rats. A return to normal weight bearing resulted in some recovery from cartilage degradation. However, radiation delivered as both a single challenge and when combined with HLU resulted in chronic cartilage damage. These findings suggest that radiation exposure during spaceflight leads to and/or impairs recovery of cartilage upon return to reloading, generating long-term joint problems for astronauts.

Use of soybean meal and papain to partially replace animal protein for culturing three marine fish species: Fish growth and water quality.

The main aim of this study was to investigate the feasibility of using soybean meal added with papain to replace half of the fishmeal used in the moist pellets (49% fishmeal and 45% trash fish) developed by the Hong Kong Agriculture, Fisheries and Conservation Department (AFCD) for culturing marine fish. Gold-lined seabream (Rhabdosargus sarba), brown spotted grouper (Epinephelus bleekeri) and pompano (Trachinotus blochii) were farmed at one of the research stations (Kat-O) of AFCD, for a period of 340 days. Results indicated that diets containing papain resulted in better fish growth (reflected by relative weight gain and feed conversion ratio) than diets without papain. In general, wet weight gain of fish depends on the amount of papain added in diet rather than the diet composition. Soybean used in conjunction with papain also contributed to a more effective growth than fish fed with the moist pellets alone. A laboratory experiment (using tanks) was conducted to study the effects of the diets on concentrations of ammonia, nitrite and nitrate in the tank water. Results showed that concentrations of ammonia and nitrate were significantly lower (p < 0.05) when the fish were fed with papain-supplemented (with or without soybean meal) diets. It is envisaged that by using plant protein incorporated with enzymes could promote better growth of marine fish and lower the adverse impact of trash fish and fishmeal on water quality of the mariculture zones.

Virological response to peramivir treatment in adults hospitalised for influenza-associated lower respiratory tract infections.

An open-label trial on intravenous peramivir was conducted among adult patients hospitalised for influenza-associated lower respiratory tract complications (LRTCs). Virus culture and quantitative reverse transcription PCR (qRT-PCR) were performed serially until Day 10. Peramivir treatment was associated with viral RNA decline as well as culture and RNA negativity, which occurred at rates comparable with those of oseltamivir: by Day 5, viral load decline -2.5 log10 copies/mL [ßinteraction -0.071, standard error (SE) 0.121, 95% confidence interval (CI) -0.309 to 0.167]; culture-negative, 94% (vs. 95%); and RNA-negative, 44% (vs. 36%). Extended treatment of >5 days was required in 69% of cases because of slow clinical resolution and viral clearance in LRTCs. Peramivir was well tolerated. These data are useful for future trial design in this unique population.

Cortical thinning and progressive cortical porosity in female patients with systemic lupus erythematosus on long-term glucocorticoids: a 2-year case-control study.

UNLABELLED: In this study, we characterized longitudinal changes of volumetric bone mineral density and cortical and trabecular microstructure at the distal radius using HR-pQCT in female systemic lupus erythematosus (SLE) patients on long-term glucocorticoids. Cortical thinning and increased cortical porosity are the major features of longitudinal microstructural deterioration in SLE patients. INTRODUCTION: The study aims to characterize longitudinal changes of volumetric bone mineral density (vBMD) and bone microstructure at distal radius in female systemic lupus erythematosus (SLE) patients on long-term glucocorticoids. METHODS: This 2-year case-control study consisted of 166 premenopausal subjects (75 SLE patients and 91 controls) and 79 postmenopausal subjects (44 SLE patients and 35 controls). We obtained areal BMD (aBMD) by dual-energy X-ray absorptiometry at multiple skeletal sites and indices of vBMD and microstructure at distal radius by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, 12 and 24 months. RESULTS: In either premenopausal or postmenopausal subjects, changes in aBMD did not differ between patients and controls except that decrease in aBMD at total hip at 24 months in premenopausal patients was significantly higher. In premenopausal subjects, decrease in cortical area (-0.51 vs. -0.06 %, p = 0.039) and thickness (-0.63 vs. 0.02 %, p = 0.031) and increase in cortical porosity (21.7 vs. 7.16 %, p = 0.030) over study period were significantly larger in patients after adjustment of age and body mass index. Decreased in trabecular vBMD was significantly less (-0.63 vs. -2.32 %, p = 0.001) with trabecular microstructure better maintained in patients. In postmenopausal subjects, decrease in cortical vBMD (-2.66 vs. -1.56 %, p = 0.039) and increase in cortical porosity (41.6 vs. 16.3 %, p = 0.021) were significantly higher in patients, and there was no group-wise difference in change of trabecular microstructure. CONCLUSION: Longitudinal microstructural deterioration in SLE is characterized by cortical thinning and increased cortical porosity. Cortical bone is an important source of bone loss in SLE patients on glucocorticoids.

Density, structure, and strength of the distal radius in patients with psoriatic arthritis: the role of inflammation and cardiovascular risk factors.

UNLABELLED: We investigated the densitometric and microstructural features of the distal radius in psoriatic arthritis (PsA) patients using high-resolution peripheral quantitative computed tomography. PsA patients have unique bone microstructural deficits, manifested as lower cortical bone density and higher cortical porosity, which are associated with a propensity to bone fragility. INTRODUCTION: The aim of this study was to investigate the densitometric, geometric, microstructural, and biomechanical features of the distal radius in psoriatic arthritis (PsA) patients. METHODS: This study cohort consisted of 53 PsA patients (24 males and 29 females), with an average age of 53.1 years and 53 gender- and age-matched controls. Areal bone mineral density (aBMD) of the hip, lumbar spine, and ultradistal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius to obtain measures of volumetric BMD (vBMD), microstructure, and derived biomechanical indices. RESULTS: There were no significant between-group differences in aBMD at the femoral neck, total hip, and ultradistal radius, while aBMD at the lumbar spine was significantly higher in patients. The only indices indicating compromised bone quality in PsA patients were related to cortical bone quality. Cortical vBMD were -3.8% significantly lower, while cortical pore volume, porosity index, and pore diameter were 108, 79.5, and 8.6%, respectively, significantly higher in patients. Cortical stress was marginally lower (-1.3%, p = 0.077) in patients with stress significantly more unevenly distributed (4.9%, p = 0.035). Endocortical perimeter and cortical pore volume were significantly higher in patients with vertebral fracture. Deficits in cortical bone quality were associated with indices of disease activity/severity and were more prominent in patients with type 2 diabetes mellitus or hypertension. CONCLUSIONS: There is an intertwined relationship between chronic inflammation, cardiovascular risk factors, and bone loss in PsA. PsA patients seem to have unique bone microstructural deficits which are associated with a propensity to bone fragility.

Is benchmarking possible in audit of early outcomes after operations for head and neck cancer?

There is a need for a validated means of adjusting for case mix in morbidity audits of patients with cancer of the head and neck. To address this, we did a multicentre audit of 3 U.K. NHS cancer networks that treat patients with head and neck cancer, to compare the incidence of early adverse postoperative outcomes and to develop a means of adjusting for case mix. We did a retrospective and prospective audit of the case notes of 901 consecutive patients who had 1034 operations for squamous cell carcinoma (SCC) of the head and neck under general anaesthesia at 3 NHS hospitals. Analysis of raw data showed postoperative 30-day mortality (n=17) to be consistent between sites (1.7%-1.9%) but 30-day complication rates varied more (34%-49%). Logistic regression models predicting morbidity discriminated well (area under the curve 0.74-0.76). Adjusted morbidity rates for the 3 units were compared on a funnel plot with 95% and 99% confidence intervals to account for random variation. It is possible to benchmark surgical performance by focusing on early postoperative outcomes in head and neck surgery. Morbidity is common and usually has a considerable impact on recovery, bed occupancy, cost, and the patient's perception of the quality of care.

Identification of appropriate outcome indices in head and neck cancer and factors influencing them.

Audit of early postoperative outcomes adjusted for patient case mix is still in its infancy in head and neck surgery. Nevertheless the role for audit of early postoperative outcomes is obvious. The primary outcome measure of this study was to identify factors that are associated with early mortality or morbidity after surgery for head and neck squamous cell carcinoma (HNSCC). The secondary outcome measure was to develop a pilot score that allows for risk-adjustment of outcome data to facilitate departmental audit. In this series the mortality rate was low (2.8%), in keeping with other published series. Complications, including those causing death, occurred after 38.1% of operations. Independent risk factors for mortality on logistic regression were shown to be previous HNSCC (P=0.03), estimated blood loss (l) (P=0.03), and extracapsular spread (P=0.05). Age (P=0.01), tracheostomy (P<0.01), estimated blood loss (l) (P=0.05), and duration of anaesthesia (P<0.01) were independent predictors of complications. Models predicting for risk demonstrated good discrimination (area under the curve statistics) for mortality (0.86) and morbidity (0.81). These pilot scores need external validation and may herald a means of facilitating risk-adjustment in the audit of early outcomes, allowing meaningful comparison of surgeons and their units over time.

Incidence of and risk factors for non-vertebral and vertebral fracture in female Chinese patients with systemic lupus erythematosus: a five-year cohort study.

OBJECTIVE: The objective of this paper is to investigate the incidence of both non-vertebral and vertebral fracture in female patients with systemic lupus erythematosus (SLE) and to identify risk factors for incident fracture. METHODS: In a five-year prospective study of 127 female Chinese SLE patients with an average age of 46.9 years (SD: 10.1 years), information on potential risk factors, including demographics, clinical data and bone mineral density (BMD) at lumbar spine and hip by dual-energy X-ray absorptiometry was collected at baseline. At follow-up, participants reported incident non-vertebral fracture during the study period. Semi-quantitative analysis was used to determine incident vertebral fracture on lateral thoracic and lumbar radiographs, defined as any vertebral body graded normal at baseline and at least mildly deformed (20%-25% reduction or more in any vertebral height) at follow-up. RESULTS: Nine incident non-vertebral fractures occurred in eight patients during the study period. Six patients had one or more incident vertebral fractures. The incidence of non-vertebral and vertebral fracture was 1.26 and 0.94 per 100 patient-years, respectively. In multivariate logistic analyses, independent variables associated with incident non-vertebral fracture were duration of glucocorticoid use and prevalent lumbar spine osteoporosis, while risk factors associated with incident vertebral fracture were higher organ damage and prevalent lumbar spine osteoporosis. CONCLUSIONS: The incidence of fracture in SLE patients is lower than the prevalence reported in cross-sectional studies. Lumbar spine BMD appears to have a stronger relationship with incident fracture than hip BMD. This warrants further investigation regarding the optimal site of BMD measurement when predicting fracture risk in SLE patients.

Race/ethnic differences in associations between bone mineral density and fracture history in older men.

SUMMARY: To determine whether there are race/ethnic differences in bone mineral density (BMD) by fracture history in men aged 65 years and older, we performed cross-sectional analysis in five large independent cohorts. Low BMD was associated with a higher prevalence of fracture in all cohorts, and the magnitude of the BMD differences by fracture status was similar across groups. INTRODUCTION: We aimed to determine whether there are race/ethnic and geographic differences in bone mineral density by fracture history in men aged 65 years and older. METHOD: The datasets included the Osteoporotic Fractures in Men (MrOS) Study (5,342 White, 243 African-American, 190 Asian, and 126 Hispanic), MrOS Hong Kong (1,968 Hong Kong Chinese), Tobago Bone Health Study (641 Afro-Caribbean), Namwon Study (1,834 Korean), and Dong-gu Study (2,057 Korean). The two Korean cohorts were combined. RESULTS: The prevalence of self-reported non-traumatic fracture was US white, 17.1 %; Afro-Caribbean, 5.5 %; US African-American, 15.1 %; US Hispanic, 13.7 %; US Asian, 10.5 %; Hong Kong Chinese, 5.6 %, and Korean, 5.1 %. The mean differences in hip and lumbar spine BMD between subjects with fracture and without fracture were statistically significant in all cohorts except US African American and US Asian men. There was a significant race/ethnic interaction for lumbar spine BMD by fracture status (p for interaction = 0.02), which was driven by the small number of Hispanic men. There was no interaction for femoral neck or total hip BMD. There were no significant race/ethnic differences in the odds ratio of fracture by BMD. CONCLUSIONS: Low BMD was associated with a higher prevalence of fracture in all cohorts and the magnitude of the BMD differences by fracture status was similar across groups suggesting homogeneity in the BMD-fracture relationship among older men.

Revisiting the dioecy-polyploidy association: alternate pathways and research opportunities.

The evolutionary transition from hermaphroditism (combined sexes) to dioecy (separate sexes) is associated with whole genome duplication (polyploidy) in several flowering plant genera. Moreover, there is evidence for transitions in the opposite direction, i.e. a loss of dioecy with an increase in ploidy. Here, we review evidence for these associations, synthesize previous ideas on the mechanism underlying the patterns and explore alternative pathways. Specifically, we examine potential ecological and genetic mechanisms, differentiated by whether ploidy or gender (functional sex expression of the plant) changes are the primary cause and whether the effect is direct or indirect. An analysis of 22 genera variable for both ploidy and gender indicates that gender monomorphism (hermaphroditism, monoecy) is more common among diploid than polyploid species, whereas gender dimorphism (dioecy, gynodioecy, subdioecy) is more frequent among polyploid species. The transition from diploid hermaphroditic to polyploid gender-dimorphic taxa may arise directly through changes in gender as a result of genome duplication through genomic rearrangements or homeologous recombination, or changes in gender may result in increased unreduced gamete production leading to polyploid formation. Alternatively, the transition may occur through the indirect effects of genome duplication on mating system and inbreeding depression, which favor selection for unisexuality, or habitat shifts associated with unisexuality may simultaneously cause increased unreduced gamete production. Novel mechanisms for transitions in the opposite direction (from dioecy to hermaphroditism with increase in ploidy) include disruption of genetic sex determination and the benefits of reproductive assurance. We highlight key questions requiring further attention and promising approaches for answering them and better clarifying the genesis of sexual system polyploidy associations. See also the sister article focusing on animals by Wertheim et al. in this themed issue.