Boyle's Law ignores dynamic processes in governing barotrauma in fish.

The expansion and potential rupture of the swim bladder due to rapid decompression, a major cause of barotrauma injury in fish that pass through turbines and pumps, is generally assumed to be governed by Boyle's Law. In this study, two swim bladder expansion models are presented and tested in silico. One based on the quasi-static Boyle's Law, and a Modified Rayleigh Plesset Model (MRPM), which includes both inertial and pressure functions and was parametrised to be representative of a fish swim bladder. The two models were tested using a range of: (1) simulated and (2) empirically derived pressure profiles. Our results highlight a range of conditions where the Boyle's Law model (BLM) is inappropriate for predicting swim bladder size in response to pressure change and that these conditions occur in situ, indicating that this is an applied and not just theoretical issue. Specifically, these conditions include any one, or any combination, of the following factors: (1) when rate of pressure change is anything but very slow compared to the resonant frequency of the swim bladder; (2) when the nadir pressure is near or at absolute zero; and (3) when a fish experiences liquid tensions (i.e. negative absolute pressures). Under each of these conditions, the MRPM is more appropriate tool for predicting swim bladder size in response to pressure change and hence it is a better model for quantifying barotrauma in fish.

The effects of simulated hydropower turbine rapid decompression on two Neotropical fish species.

Barotrauma is a major cause of injury and mortality of fish as they pass through hydropower turbines. Current understanding of hydropower related barotrauma is biased towards northern temperate and southern subtropical species with single chambered swim bladders, specifically North American and Australian species, respectively. Today, unprecedented hydropower development is taking place in Neotropical regions where many species have complex multi-chambered swim bladder architecture. This study investigated barotrauma in two dual-chambered physostomous Neotropical fish (pacu, Piaractus mesopotamicus, and piracanjuba, Brycon orbignyanus) exposed to rapid (< 1 s) decompression at different Ratios of Pressure Change (RPC), using a hypo-hyperbaric chamber. The incidence and intensity (percentage surface area of organ affected) of injury and physiological and behavioural response (hereafter just response) of each species immediately after decompression was assessed. Twenty-two injury types (e.g. gill haemorrhage and exophthalmia) and eight response categories (e.g. rising to the surface and loss of orientation) were identified and the influence of: 1) species, 2) RPC, and 3) swim bladder rupture on each was quantified. There was considerable interspecific difference with emboli type injuries occurring more frequently in piracanjuba, but injury intensity tending to be higher in pacu. Both swim bladder chambers tended to rupture in piracanjuba but only the anterior chamber in pacu. RPC was positively correlated with response, incidence and intensity of several injury types for both species with some injuries occurring at very low RPC (e.g. 50 % probability of swim bladder rupture at 2.2 and 1.75 for piracanjuba and pacu, respectively). Multiple responses (e.g. loss of orientation) and injuries (e.g. eye haemorrhage) were correlated with swim bladder rupture suggesting gas venting into the body cavity likely causes secondary injury. When directly comparing our results with those available in the published literature, both pacu and piracanjuba appear to be more susceptible to barotrauma than previously studied subtropical and temperate species.

A cost analysis of treating postoperative periprosthetic femoral fractures following hip replacement surgery in a UK tertiary referral centre.

AIM: This study aims to evaluate costs associated with periprosthetic femoral fracture (PFF) treatment at a UK tertiary referral centre. METHODS: This study included 128 consecutive PFFs admitted from 02/04/2014-19/05/2020. Financial data were provided by Patient Level Information and Costing Systems. Primary outcomes were median cost and margin. Secondary outcomes were length of stay, blood transfusion, critical care, 30-day readmission, 2-year local complication, 2-year systemic complication, 2-year reoperation and 30-day mortality rates. Statistical comparisons were made between treatment type. Statistical significance was set at p<0.05. RESULTS: Across the cohort, median cost was £15,644.00 (IQR £11,031.00-£22,255.00) and median loss was £3757.50 (£599.20-£8296.20). The highest costs were ward stay (£3994.00, IQR £1,765.00-£7,013.00), theatre utilisation (£2962.00, IQR £0.00-£4,286.00) and overheads (£1705.10, IQR £896.70-£2432.20). Cost (£17,455.00 [IQR, £13,194.00-£23,308.00] versus £7697.00 [IQR £3871.00-£10,847.00], p<0.001) and loss (£4890.00 [IQR £1308.00-£10,009.00] versus £1882.00 [IQR £313.00-£3851.00], p = 0.02) were greater in the operative versus the nonoperative group. There was no difference in cost (£17,634.00 [IQR £12,965.00-£22,958.00] versus £17,399.00 [IQR £13,394.00-£23,404.00], p = 0.98) or loss (£5374.00 [IQR £1950.00-£10,143.00] versus £3860.00 [IQR -£95.50-£7601.00], p = 0.21) between the open reduction and internal fixation (ORIF) and revision groups. More patients required blood transfusion in the operative versus the nonoperative group (17 [17.9%] versus 0 [0.0%], p = 0.009). There was no difference in any clinical outcome between the ORIF and revision groups (p>0.05). CONCLUSION: PFF treatment costs are high with inadequate reimbursement from NHS tariff. Work is needed to address this disparity and reduce hospital costs. Cost should not be used to decide between ORIF and revision surgery.

Normothermic ex vivo perfusion of the limb allograft depletes donor leukocytes prior to transplantation.

INTRODUCTION: The donor immune compartment plays a central role in graft rejection of the vascularised composite allograft (VCA) by contributing to 'direct presentation'. Using our limb ex vivo normothermic machine perfusion (EVNP) protocol designed for prolonged allograft preservation, this study aimed to assess whether donor leukocytes responsible for allograft rejection are mobilised from the donor compartment. METHODS: Five genetically different pig forelimbs underwent perfusion via the brachial and radial collateral artery for 6 h after 2 h of cold storage. Oxygenated haemodilute leucocyte-deplete blood was recirculated at normothermia using an extracorporeal perfusion system. Tissue perfusion was evaluated clinically and biochemically via blood perfusate. The temporal kinetics of donor leucocyte extravasation, cytokine secretion and cell-free DNA was characterised in the circulating perfusate. RESULTS: Flow cytometry revealed increasing populations of viable leukocytes over time, reaching 49 billion leukocytes by 6 h. T (3.0 × 109 cells) and B cells (3.1 × 108 cells) lymphocytes, monocytes (2.7 × 109 cells), granulocytes (8.1 × 109 cells), NK (6.3 × 108) and γδ (8.1 × 108) cells were all identified. Regulatory T cells comprised a minor population (1.6 × 107 cells). There was a cumulative increase in pro-inflammatory cytokines suggesting that the donor limb has the capacity to elicit significant inflammatory responses that could contribute to leucocyte activation and diapedesis. CONCLUSION: EVNP not only acts as a preservation tool, but could also be utilized to immunodeplete the VCA allograft prior to transplantation. This has clinical implications to mitigate acute rejection and prevent graft dysfunction and supports the future application of machine perfusion in graft preservation and immune modulation.

Randomized preclinical study of machine perfusion in vascularized composite allografts.

BACKGROUND: Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health. METHODS: A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression. RESULTS: NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70. CONCLUSION: Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.

Selective fish passage: Restoring habitat connectivity without facilitating the spread of a non-native species.

River managers are challenged to address two key threats to freshwater biodiversity. The first is the effects of habitat fragmentation by instream structures, such as dams and weirs, that disrupt migrations and impact species distributions. The second is the impact of non-native species on native species and ecological processes. However, mitigating anthropogenic habitat fragmentation through the installation of passage facilities can facilitate the invasion and spread of non-native species. This study compared the potential of two existing low-cost fish passage technologies designed for sloping weirs, a cylindrical bristle cluster (CBC) array and horizontally oriented studded tiles, to facilitate upstream movement of native European fish while preventing dispersal of non-native American signal crayfish (Pacifastacus leniusculus); thus providing a selective fish passage solution. Crayfish movement and passage was experimentally quantified at a Crump weir installed in a recirculating flume under two velocity regimes (low and high), without (control) and with the addition of either a CBC array or studded tiles. Results were compared to passage efficacy (PE) data for native fish species for both technologies (existing data). Most (84.4%) crayfish were active during the trials, exhibiting frequent up and downstream movements below the weir. During control conditions under the high velocity regime, high velocities (ca. 2.39 m s-1) prevented crayfish reaching the foot of the weir (PE: 0%). Under the low velocity regime, relatively low velocities (ca. 0.74 m s-1) at the weir crest prevented most crayfish from passing (PE: 10-16%). Crayfish movement speed and total distance moved were lower under the high than the low velocity regime. Neither fish pass technology improved crayfish maximum distance of ascent on the downstream weir face or PE under either velocity regime. Under comparable conditions to the high velocity regime tested here, previous studies have shown both technologies improve PE for native fish. Hence, both CBC arrays and studded tiles would likely function as suitable selective fish passes where the conservation objective is not to aid the spread of non-native crayfish. Additional passage inhibiting technologies will be required at sites where complete blockage of crayfish movement is required.

Hendra in the Hunter Valley.

In June 2019 the first equine case of Hendra virus in the Hunter Valley, New South Wales, Australia was detected. An urgent human and animal health response took place, involving biosecurity measures, contact tracing, promotion of equine vaccinations and investigation of flying fox activity in the area. No human or additional animal cases occurred. Equine vaccination uptake increased by over 30-fold in the surrounding region in the three months following the case. Black flying fox and grey-headed flying fox species were detected in the Valley. The incident prompted review of Hendra virus resources at local and national levels. This event near the "horse capital of Australia", is the southernmost known equine Hendra case. Management of the event was facilitated by interagency collaboration involving human and animal health experts. Ongoing One Health partnerships are essential for successful responses to future zoonotic events.

Chloride inputs to the North Saskatchewan River watershed: the role of road salts as a potential driver of salinization downstream of North America's northern most major city (Edmonton, Canada).

Multiple anthropogenic activities are driving the salinization of freshwater environments threatening water resources worldwide. Accordingly, this research will first examine the spatial and temporal variability of major ions (i.e. Ca2+, Mg2+, Na+, K+, SO42-, CO32-, and HCO3-) upstream and downstream of the northernmost major city in North America (Edmonton, Canada). Second, this research will estimate the relative contributions of the major sources of chloride (Cl), the main constituent of road deicers, to the sub-basin around Edmonton. Monthly water quality data was for three sites on the North Saskatchewan River (NSR): Rocky Mountain House (RMH - downstream of the Rocky Mountain headwaters), Devon Bridge (upstream of Edmonton) and Pakan Bridge (downstream of Edmonton). Change ratios investigate the downstream alterations of major ions at Pakan and Devon, relative to RMH. Seasonal Kendall tests examine temporal trends (1987-2017). A mass-balance approach then quantifies the major sources of Cl in the sub-basin of the NSR between Devon and Pakan. Progressing from the Rocky Mountain headwaters (at RMH) to downstream of Edmonton (at Pakan), Cl- increased by >5.5 times, Na+ by 4.8 times and K by 2.7 times. No significant temporal trends for Cl-, Na+ and K+ were evident at Devon (upstream of Edmonton), whereas all three significantly increased at Pakan (downstream of Edmonton). Deicers (54%), agriculture (20%), along with waste water treatment plant and industrial effluent (15%) were the largest Cl sources in the NSR Devon-Pakan sub-basin. In total, 77 Gg yr-1 of Cl (or 6 t km2 yr-1) is added to the Devon-Pakan sub-basin, of which, 43 Gg yr-1 is retained. Understanding and managing the major drivers of freshwater salinization will be of increasing importance in the 21st century owing to the potential salinization of freshwater resources in the context of a changing climate.

Oral Medicine for undergraduate dental students in the United Kingdom and Ireland-A curriculum.

INTRODUCTION: Oral Medicine focuses on care for patients with chronic, recurrent and medically related disorders of the orofacial region that are distinct from diseases of the periodontal and tooth tissues, with an emphasis on non-surgical management. At present, there are no shared outcomes for Oral Medicine to define the standards to be achieved before new graduates become registered dentists engaged with ongoing professional development. CURRICULUM: We present a consensus undergraduate curriculum in Oral Medicine agreed by representatives from 18 Dental Schools in the United Kingdom and Republic of Ireland. The scope of Oral Medicine practice includes conditions involving the oral mucosa, salivary glands, neurological system or musculoskeletal tissues that are not directly attributable to dental (tooth and periodontium) pathology. Account is taken of the priorities for practice and learning opportunities needed to support development of relevance to independent clinical practice. The outcomes triangulate with the requirements set out by the respective regulatory bodies in the UK and Republic of Ireland prior to first registration and are consistent with the framework for European undergraduate dental education and greater harmonisation of dental education. CONCLUSIONS: This curriculum will act as a foundation for an increasingly shared approach between centres with respect to the outcomes to be achieved in Oral Medicine. The curriculum may also be of interest to others, such as those responsible for the training of dental hygienists and dental therapists. It provides a platform for future collective developments with the overarching goal of raising the quality of patient care.

Perceived Neighborhood Environmental Factors That Maximize the Effectiveness of a Multilevel Intervention Promoting Physical Activity Among Latinas.

PURPOSE: This study tested whether a multilevel physical activity (PA) intervention had differential effects on PA according to participants' perceptions of their neighborhood environment. DESIGN: Two-group cluster randomized controlled trial. SETTING: San Diego, California. SUBJECTS: Analytical sample included 319 Latinas (18-65 years) from churches randomized to the following conditions: PA (n = 8 churches, n = 157 participants) or attention control (n = 8 churches, n = 162 participants). INTERVENTION: Over 12 months, PA participants were offered free PA classes (6/wk), while attention control participants were offered cancer prevention workshops. MEASURES: Baseline and 12-month follow-up measures included self-report and accelerometer-based moderate to vigorous physical activity (MVPA), sociodemographics, and perceived neighborhood environment variables. ANALYSIS: Mixed-effects models examined each PA outcome at 12-month follow-up, adjusted for church clustering, baseline PA, and sociodemographics. We tested interactions between 7 baseline perceived environment variables and study condition. RESULTS: Neighborhood esthetics was the only significant moderator of intervention effects on accelerometer-based MVPA and self-report leisure-time MVPA. Participants in the PA intervention had significantly higher PA at follow-up than attention control participants, only when participants evaluated their neighborhood esthetics favorably. CONCLUSION: Perceived neighborhood esthetics appeared to maximize the effectiveness of a multilevel PA intervention among Latinas. For sustainable PA behavior change, the environments in which Latinas are encouraged to be active may need to be evaluated prior to implementing an intervention to ensure they support active lifestyles.

Where and when adolescents are physically active: Neighborhood environment and psychosocial correlates and their interactions.

Female adolescents are less active than male peers in certain contexts including the neighborhood. Adolescents' physical activity can be explained by interactions between environmental and psychosocial factors, but few studies have tested such interactions in relation to context-specific behaviors. This study tested interactions between neighborhood environmental and psychosocial factors in relation to adolescents' context-specific physical activity. Data were collected in 2009-11 from 910 adolescents and a parent/guardian residing in the Baltimore/Seattle regions. Measures included adolescent-reported neighborhood leisure-time physical activity (LTPA) and non-neighborhood LTPA, accelerometer-based non-school moderate-to vigorous-physical activity (MVPA), psychosocial factors, and objective and parent-perceived neighborhood environmental factors. Gender-stratified mixed effects linear models tested associations of 6 environmental and 4 psychosocial factors and their interactions in relation to each physical activity outcome. The psychosocial factors had consistent associations with the physical activity outcomes but the environmental correlates were context-specific. Decisional balance (weighing of pros and cons of physical activity) moderated the association between recreation facility density and neighborhood LTPA among females, with a negative association only among those with high decisional balance (pros outweighed cons). Decisional balance also moderated associations of neighborhood walkability with non-school MVPA among females and non-neighborhood LTPA among males, with positive associations only among those with high decisional balance. Results support context-specific ecological models of physical activity. Targeting environmental factors that may promote opportunities for physical activity in specific contexts as well as adolescent decision-making may help promote their physical activity in those contexts, potentially leading to increased overall physical activity.

Temperament and body weight from ages 4 to 15 years.

BACKGROUND/OBJECTIVES: In adulthood, conscientiousness and neuroticism are correlates of body weight and weight gain. The present research examines whether the childhood antecedents of these traits, persistence and negative reactivity, respectively, are associated with weight gain across childhood. We likewise examine sociability as a predictor of childhood weight gain and whether these three traits are associated with weight concerns and weight-management strategies in adolescence. SUBJECTS/METHODS: Participants (N=4153) were drawn from the Longitudinal Study of Australian Children, an ongoing, population-based study of child and family health and well-being. At the baseline assessment, caregivers reported on their child's temperament. At every assessment from ages 4-5 to 14-15 years, study children were weighed and measured by trained staff; there were up to six biennial assessments of body mass index and waist circumference. At ages 14-15 years, study children (n=2975) also self-reported on their weight concerns and weight-management strategies. RESULTS: Study children rated lower in persistence or higher in negative reactivity in early childhood gained more weight between the ages of 4 and 15 years. Sociability was associated with weight gain among girls but not among boys. Lower persistence and higher negative reactivity at ages 4-5 years were also associated with greater weight concerns, restrained eating and use of unhealthy weight-management strategies at ages 14-15 years. CONCLUSIONS: Childhood traits related to conscientiousness and neuroticism are associated with objective weight gain across childhood and with concerns and strategies to manage weight in adolescence. These results are consistent with a lifespan perspective that indicates that trait psychological functioning contributes to health-related markers from childhood through old age.

Does the social environment moderate associations of the built environment with Latinas' objectively-measured neighborhood outdoor physical activity?

Favorable perceptions of the built and social neighborhood environment may promote outdoor physical activity (PA). However, little is known about their independent and interactive effects on neighborhood-specific outdoor PA. We examined associations of perceived built and social neighborhood environment factors, and their interactions, with objectively-measured neighborhood outdoor moderate-to-vigorous physical activity (MVPA) among a sample of Latina women in San Diego, CA. Analyses included baseline data collected in 2011-2013 from 86 Latinas with ≥ 2 days of combined accelerometer and global positioning system data and complete survey measures. We examined objective neighborhood outdoor MVPA within 500-meter home buffers. Generalized linear mixed models examined associations of 3 perceived built (e.g., sidewalk maintenance) and 3 social environmental (e.g., safety from crime) factors with engaging in any daily neighborhood outdoor MVPA. Models tested interactions between the built and social environmental factors. Although the perceived neighborhood environmental factors were not significantly related to daily neighborhood outdoor MVPA, we found 2 significant interactions: perceived sidewalk maintenance x safety from crime (p = 0.05) and neighborhood aesthetics x neighborhood social cohesion (p = 0.03). Sidewalk maintenance was positively related to daily neighborhood outdoor MVPA only among Latinas that reported low levels of safety from crime. Neighborhood aesthetics was positively related to daily neighborhood outdoor MVPA only among Latinas with high neighborhood social cohesion. Findings suggest several built and social environmental factors interact to influence Latinas' neighborhood outdoor MVPA. Interventions are needed targeting both built and social neighborhood environmental factors favorable to outdoor PA in the neighborhood.

Intra-articular steroid injection for osteoarthritis of the hip prior to total hip arthroplasty : is it safe? a systematic review.

AIMS: Using a systematic review, we investigated whether there is an increased risk of post-operative infection in patients who have received an intra-articular corticosteroid injection to the hip for osteoarthritis prior to total hip arthroplasty (THA). METHODS: Studies dealing with an intra-articular corticosteroid injection to the hip and infection following subsequent THA were identified from databases for the period between 1990 to 2013. Retrieved articles were independently assessed for their methodological quality. RESULTS: A total of nine studies met the inclusion criteria. Two recommended against a steroid injection prior to THA and seven found no risk with an injection. No prospective controlled trials were identified. Most studies were retrospective. Lack of information about the methodology was a consistent flaw. CONCLUSIONS: The literature in this area is scarce and the evidence is weak. Most studies were retrospective, and confounding factors were poorly defined or not addressed. There is thus currently insufficient evidence to conclude that an intra-articular corticosteroid injection administered prior to THA increases the rate of infection. High quality, multicentre randomised trials are needed to address this issue. Cite this article: Bone Joint J 2016;98-B:1027-35.

FT-Raman Spectroscopy Study of the Remineralization of Microwave-Exposed Artificial Caries.

Dental caries is a microbially mediated disease that can result in significant tooth structure degradation. Although the preponderance of lesions is treated by surgical intervention, various strategies have been developed for its noninvasive management. Here, we use a novel approach for noninvasive treatment based on killing Streptococcus mutans with high-frequency microwave energy (ME). The rationale for this approach is based on modulating the pH of caries to a physiological state to enable spontaneous tooth remineralization from exogenous sources. In the present study, after demonstrating that ME kills >99% of S. mutans in planktonic cultures, 8 enamel slabs were harvested from a single tooth. Baseline mineral concentration at each of 12 points per slab was obtained using Fourier transform (FT)-Raman spectroscopy. Surface demineralization was subsequently promoted by subjecting all samples to an S. mutans acidic biofilm for 6 d. Half of the samples were then exposed to high-frequency ME, and the other half were used as controls. All samples were next subjected to a remineralization protocol consisting of two 45-min exposures per 24-h period in tryptic soy broth followed by immersion in a remineralizing solution for the remaining period. After 10 d, samples were removed and cleaned. FT-Raman spectra were again obtained at the same 12 points per sample, and the mineral concentration was determined. The effect of the remineralization protocol on the demineralized slabs was expressed as a percentage of mineral loss or gain relative to baseline. The mineral concentration of the microwave-exposed group collectively approached 100% of baseline values, while that of the control group was in the order of 40%. Differences between groups were significant (P = 0.001, Mann-Whitney U test). We concluded that killing of S. mutans by ME promotes effective remineralization of S. mutans-demineralized enamel compared with controls.

Two samples for blood transfusion: single centre experience.

OBJECTIVES: The aim of this study was to evaluate the introduction of two-sample policy for transfusion at our hospital and reduction of the risk of ABO incompatible transfusion. BACKGROUND: ABO incompatible transfusion can be a fatal but avoidable event. Wrong blood in tube is a cause of ABO incompatible transfusion and there are various strategies available to try and expunge this event. METHODS: Survey of policy/practice before and after the introduction of a two-sample policy. RESULTS: Staff training is inadequate in reducing the risk of ABO incompatible transfusion. A two-sample policy was introduced and does not significantly increase workload or use of group O blood and does not compromise patient safety by causing delay in blood provision. Post hoc analysis confirms good understanding of the policy by medical staff. Observation of medical staff taking transfusion samples demonstrated consistent deviation from policy, enforcing the need for confirmatory samples. CONCLUSION: A two-sample policy adds an extra layer of safety to transfusion practice and can be introduced without creating new problems.

Loss of the proapoptotic BH3-only protein BCL-2 modifying factor prolongs the fertile life span in female mice.

The duration of the female fertile life span is influenced by the number of oocytes stored in the ovary as primordial follicles. Cell death, both during ovarian development in the embryo and in the postnatal ovary, plays a critical role in determining how many primordial follicles are established and maintained within the ovary. However, the roles of individual apoptotic regulators in mediating cell death within the ovary have not yet been characterized. In this study, gene targeted mice were used to investigate the role of BCL-2-modifying factor (BMF), a proapoptotic protein belonging to the BH3-only subgroup of the BCL-2 family, in determining the number of primordial follicles maintained in the adult ovary and the length of the fertile life span. Stereological analysis of ovaries showed that Bmf(-/-) mice had significantly more primordial follicles than wild-type (WT) control animals at Postnatal Days 100, 200, 300, and 400 but not at Day 20. No differences were observed between WT and Bmf(-/-) mice in the number of ova shed following ovulatory stimulation with exogenous gonadotropins. Bmf(-/-) females were fertile and produced the same number pups/litter as WT females, but Bmf(-/-) females produced litters more frequently and consequently more offspring than WT females over a 6-mo period. Furthermore, the fertile life span of Bmf(-/-) females was significantly extended compared to WT females. Our findings support an important role for BMF in determining the number of primordial follicles maintained in the ovary throughout adult reproductive life and thus indicate that the length of female fertility may be extended by increasing the number of primordial follicles maintained within the ovary through inhibition of BMF.