Medial arch instability/internal foot overload association with non-insertional Achilles tendinopathy and the 'Zone of Conflict Theory'.

BACKGROUND: Non insertional Achilles tendinopathy [AT] is a degenerative condition that is prevalent in runners. 30% have no preceding history and many runners do not develop AT. Overuse, pronation, and compromised blood supply are hypothesised as causal. The exact precipitant is still unknown. The link between medial arch instability and AT has not been made. The purpose of this study was to investigate the association between spring ligament (SL) laxity and first ray (FRI) instability, and the presence of (AT). METHODS: Ethical approval was obtained. Patients were identified from hospital databases for unilateral AT, allowing the opposite unaffected foot to be used as an internal control. SL laxity was measured using the lateral translation score and FRI was measured using a modified digital Klauemeter. Ultrasound was used to assess the tendoachilles [TA] in affected vs unaffected legs. RESULTS: 17 patients were recruited with a mean age of 55.6 and mean body mass index (BMI) of 33.3. The average symptom duration was 3.62 years. There were 12 left feet and 5 right feet. There was no statistical difference in dorsiflexion angles for the TA or the gastrocnemius. All Beighton scores < 5. Lateral translation scores, FRI scores and TA thickness was significantly greater in AT feet [p < 0.05]. More affected feet had Tibialis posterior tendon pain (TP) [p < 0.05]. CONCLUSIONS: Feet with AT exhibit higher lateral translation scores and greater FRI compared to healthy feet, and combined with previous literature evidence, suggests alteration of the subtalar axis alters force moments that may lead to an intrinsic overload of the TA, when the foot enters a "zone of conflict". Medial arch instability, in particular SL laxity and FRI, may contribute to the development of non-insertional AT and treatment of this with early arch support may prevent progressive degeneration.

Ciguatera poisoning in French Polynesia: A review of the distribution and toxicity of Gambierdiscus spp., and related impacts on food web components and human health.

Ciguatera Poisoning (CP) is a seafood poisoning highly prevalent in French Polynesia. This illness results from the consumption of seafood contaminated with ciguatoxins (CTXs) produced by Gambierdiscus, a benthic dinoflagellate. Ciguatera significantly degrades the health and economic well-being of local communities largely dependent on reef fisheries for their subsistence. French Polynesia has been the site of rich and active CP research since the 1960's. The environmental, toxicological, and epidemiological data obtained in the frame of large-scale field surveys and a country-wide CP case reporting program conducted over the past three decades in the five island groups of French Polynesia are reviewed. Results show toxin production in Gambierdiscus in the natural environment may vary considerably at a temporal and spatial scale, and that several locales clearly represent Gambierdiscus spp. "biodiversity hotspots". Current data also suggest the "hot" species G. polynesiensis could be the primary source of CTXs in local ciguateric biotopes, pending formal confirmation. The prevalence of ciguatoxic fish and the CTX levels observed in several locales were remarkably high, with herbivores and omnivores often as toxic as carnivores. Results also confirm the strong local influence of Gambierdiscus spp. on the CTX toxin profiles characterized across multiple food web components including in CP-prone marine invertebrates. The statistics, obtained in the frame of a long-term epidemiological surveillance program established in 2007, point towards an apparent decline in the number of CP cases in French Polynesia as a whole; however, incidence rates remain dangerously high in some islands. Several of the challenges and opportunities, most notably those linked to the strong cultural ramifications of CP among local communities, that need to be considered to define effective risk management strategies are addressed.

Observation of Low-Lying Isomeric States in

We report on new measurements establishing the existence of low-lying isomeric states in ^{136}Cs using γ rays produced in ^{136}Xe(p,n)^{136}Cs reactions. Two states with O(100) ns lifetimes are placed in the decay sequence of the ^{136}Cs levels that are populated in charged-current interactions of solar neutrinos and fermionic dark matter with ^{136}Xe. Xenon-based experiments can therefore exploit a delayed-coincidence tag of these interactions, greatly suppressing backgrounds to enable spectroscopic studies of solar neutrinos and dark matter.

The influence of feeding routines on the behavior of zoo-housed Sulawesi crested black macaques (Macaca nigra).

Many species thrive in captivity, yet there is still much to be assessed regarding the often-unknown stressors present that can compromise welfare. Uncovering such stressors is of paramount importance if we are to ensure the zoo environment provides the highest levels of animal welfare that will contribute to species conservation. Zoo-housed primates are subject to many potential stressors, including daily husbandry routines which they may find aversive or habituate to, regardless of their outcome. The specific aim of this study was to assess the behavioral responses to daily husbandry feeding routines on a total of 33 Sulawesi crested black macaques (Macaca nigra), across two different UK zoological collections. Group scan sampling was used to record behaviors for 30-min periods before feeding (BF), for 30 min after feeding (AF), which we began 30 min after feed provision, and for 30 min when no feeding occurred (NF). The feeding condition significantly influenced behaviors recorded and post-hoc comparisons showed that BF conditions produced significantly higher frequencies of food anticipatory related activity (FAA). Furthermore, during BF periods, behaviors associated with FAA increased during the 15 min closer to a feed. This research finds that temporal feeding events cause changes in the behavior of two independent groups of crested macaques, indicative of food anticipation activity, during 30-min periods leading up to a feed. These results have implications for how animal keeper routines and advertised zoo feeds are managed for this species within zoological collections.

Proton Compton Scattering from Linearly Polarized Gamma Rays.

Differential cross sections for Compton scattering from the proton have been measured at scattering angles of 55°, 90°, and 125° in the laboratory frame using quasimonoenergetic linearly (circularly) polarized photon beams with a weighted mean energy value of 83.4 MeV (81.3 MeV). These measurements were performed at the High Intensity Gamma-Ray Source facility at the Triangle Universities Nuclear Laboratory. The results are compared to previous measurements and are interpreted in the chiral effective field theory framework to extract the electromagnetic dipole polarizabilities of the proton, which gives α_{E1}^{p}=13.8±1.2_{stat}±0.1_{BSR}±0.3_{theo},ß_{M1}^{p}=0.2∓1.2_{stat}±0.1_{BSR}∓0.3_{theo} in units of 10^{-4} fm^{3}.

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes.

AIMS: Biomarker-driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub-classify iMB, and proffer strategies for personalized, risk-adapted therapies. METHODS: We characterized the iMB molecular landscape, including second-generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). RESULTS: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second-generation subtypes II/III/IV. Subtype II strongly associated with large-cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very-high-risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4 ) and subtype IV tumours were standard risk (80% OS) using upfront CSI-based therapies; randomized-controlled trials of upfront radiation-sparing and/or second-line radiotherapy should be considered. Seventy-five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non-DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH . iMBSHH harboured two distinct subtypes (iMBSHH-I/II ). Within the discriminated favourable-risk iMBSHH DN/MBEN patient group, iMBSHH-II had significantly better progression-free survival than iMBSHH-I , offering opportunities for risk-adapted stratification of upfront therapies. Both iMBSHH-I and iMBSHH-II showed notable rescue rates (56% combined post-relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. CONCLUSIONS: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup-dependent survival models highlight opportunities for biomarker-directed therapies.

Viewing perspective malrotation influences angular measurements on lateral radiographs of the scapula.

BACKGROUND: Accurate and reliable assessment of acromial tilt (ATA) and slope (ASA) angles have been important in the clinical evaluation of degenerative and traumatic rotator cuff tears. This study analyzed the influence of radiographic viewing perspective on the ATA and ASA and developed criteria to identify true lateral (TL) view radiographs. METHODS: Three-dimensional computed tomographic (CT) reconstructions of 52 scapulae without rotator cuff tears or osteoarthritis were studied. Digitally reconstructed radiographs (DRRs) were aligned to obtain a TL view. In 10 random scapulae, incremental ante- and retroversion and up- and downward rotation views were generated (10° increments, ±30°), and ATA and ASA were measured by 2 observers. Clinically applicable criteria were developed and validated to identify TL views. RESULTS: The mean ATA and ASA on TL views were 33°±4° (range 23°-42°) and 22°±7° (8°-43°), respectively. Mixed effect models showed that DRRs malpositioned in 20° and 30° anteversion and downward rotation decreased the ATA (P ≤ .030). DRRs malpositioned in anteversion and >10° of up- and downward rotation demonstrated a significantly decreased ASA (P ≤ .047). Intra- and interobserver reliability was excellent for TL views (intraclass correlation coefficient ≥ 0.95) but decreased with increasing viewing angle. Anatomic landmark criteria were capable of identifying TL-view radiographs with sensitivity of 81% and specificity of 82%. CONCLUSION: Both ATA and ASA were significantly affected by malposition in anteversion and downward rotation of the scapula. Reliable ASA measurement was more susceptible in up- and downward rotation than the ATA. New visual criteria can identify TL-view radiographs and should be used in future studies to ensure consistency in ATA and ASA measurement.

Female cognitive performance and mass are correlated with different aspects of mate choice in the zebra finch (Taeniopygia guttata).

A female's cognitive ability may influence her mate preferences through various mechanisms. These mechanisms include the direct effect of cognitive ability on the information-processing skills used during mate choice, and the indirect effect of cognitive ability on quality when females mate assortatively. Here, we examined whether the ability to learn a novel foraging task, a cognitive skill which has been associated with reproductive success in other capacities, was correlated with song preferences in female zebra finches (Taeniopygia guttata). Female preferences were measured in an operant testing chamber where hops on a perch triggered song playback. Females were given the choice of (1) conspecific vs. heterospecific song and (2) high-quality male vs. low-quality male conspecific song. We found that female performance on the novel foraging task was positively correlated with preference for conspecific song, but not with preference for high-quality male song. Instead, female mass was positively correlated with preference for high-quality male song, potentially signifying that female mass is a stronger predictor of female quality in assortative mating than female cognitive performance. Female mass and cognitive performance were unrelated. Our results suggest that the particular traits of a female that affect conspecific preference do not necessarily affect preference for high-quality males.

Remote Antimicrobial Stewardship: A Solution for Meeting The Joint Commission Stewardship Standard?

Purpose: The purpose of this study was to determine the time required for antimicrobial stewardship (AS) activities at a small community hospital (SCH) as well as barriers to remote AS to satisfy The Joint Commission (TJC)'s AS standard. Methods: This was a prospective chart review and time study conducted in patients identified by a clinical decision support application as potential opportunities for antimicrobial therapy modification at a SCH between December 12, 2016, and March 31, 2017. Potential interventions were communicated electronically to the clinical pharmacy specialist, who would then communicate the recommendations to the patient's provider. The primary endpoint was a time study for stewardship activities. Secondary endpoints included describing barriers encountered to remote AS as well as a cost-benefit analysis of remote AS. Results: The time study revealed an average of 11 alerts per day, 9 chart reviews per day, 8 interventions per day, and 5 minutes per chart. Seven hundred twenty-four alerts were evaluated with the most common alerts constituting opportunities for de-escalation (29%), targeted drugs (22%), positive blood cultures (18%), Intravenous (IV) to oral (PO) (17%), and antimicrobial renal monitoring (8%).Interventions were accepted (11%), accepted modified (6%), rejected (35%), or undetermined (48%). Barriers to implementation included workflow and indirect communication. For patients with accepted interventions, there was an average savings of $279.82 per patient in pharmacy charges. Conclusion: Through remote AS, a SCH can have an antimicrobial stewardship program that is in compliance with the basic elements of the TJC standard MM.09.01.01, performs daily chart review by an infectious diseases trained pharmacist to increase the quality of patient care, and achieves a mean savings of $279.82 in pharmacy charges and $1,126.26 in hospital charges per patient with accepted interventions.

Activation of the Medial Prefrontal Cortex Reverses Cognitive and Respiratory Symptoms in a Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2; Amir et al., 1999), a transcriptional regulatory protein (Klose et al., 2005). Mouse models of RTT (Mecp2 mutants) exhibit excitatory hypoconnectivity in the medial prefrontal cortex (mPFC; Sceniak et al., 2015), a region critical for functions that are abnormal in RTT patients, ranging from learning and memory to regulation of visceral homeostasis (Riga et al., 2014). The present study was designed to test the hypothesis that increasing the activity of mPFC pyramidal neurons in heterozygous female Mecp2 mutants (Hets) would ameliorate RTT-like symptoms, including deficits in respiratory control and long-term retrieval of auditory conditioned fear. Selective activation of mPFC pyramidal neurons in adult animals was achieved by bilateral infection with an AAV8 vector expressing excitatory hm3D(Gq) DREADD (Designer Receptors Exclusively Activated by Designer Drugs) (Armbruster et al., 2007) under the control of the CamKIIa promoter. DREADD activation in Mecp2 Hets completely restored long-term retrieval of auditory conditioned fear, eliminated respiratory apneas, and reduced respiratory frequency variability to wild-type (Wt) levels. Reversal of respiratory symptoms following mPFC activation was associated with normalization of Fos protein levels, a marker of neuronal activity, in a subset of brainstem respiratory neurons. Thus, despite reduced levels of MeCP2 and severe neurological deficits, mPFC circuits in Het mice are sufficiently intact to generate normal behavioral output when pyramidal cell activity is increased. These findings highlight the contribution of mPFC hypofunction to the pathophysiology of RTT and raise the possibility that selective activation of cortical regions such as the mPFC could provide therapeutic benefit to RTT patients.

Exploratory study of the role of knowledge brokers in translating knowledge to action following global maternal and newborn health technical meetings.

OBJECTIVES: There have been increasing calls for more research on interventions to successfully translate evidence-based knowledge into improved health policy and practices. This paper reports on an exploratory study of knowledge translation interventions conducted with participants of global health meetings held in Bangladesh in 2012 and in South Africa in 2013. We measured stakeholders' uptake of evidence-based knowledge in terms of their translation of this knowledge into actions around public health policy and practice. The research sought to determine whether participants shared and used knowledge from the meetings to improve health policy and practices in their settings and the factors influencing sharing and use. STUDY DESIGN: An exploratory study employed quantitative and qualitative methods of online surveys and in-depth interviews to collect data from all meeting participants. METHODS: All participants in the Bangladesh and South Africa meetings were invited to complete an online survey during the meetings and over the following six weeks. Of 411 participants in the 2012 Bangladesh meeting, 148 participants from 22 countries completed the survey. Eleven of these respondents (from eight countries) were interviewed. Of the 436 participants in the 2013 South Africa meeting, 126 respondents from 33 countries completed an online survey; none of these respondents were interviewed. RESULTS: The analysis revealed that most respondents used new knowledge to advocate for policy change (2012: 65.5%; 2013: 67.5%) or improve service quality (2012: 60.1%; 2013: 70.6%). The type of knowledge that respondents most commonly shared was clinical or scientific information (2012: 79.1%; 2013: 66.7%) and country-specific information (2012: 73.0%; 2013: 71.4%). Most 2012 respondents shared knowledge because they thought it would be useful to a co-worker or colleague (79.7%). DISCUSSION: Findings on knowledge use and sharing suggest that most respondents saw themselves as knowledge brokers or intermediaries in a position to influence the translation of knowledge into action in health policy and practices in their countries. Results suggest that supporting knowledge brokers working in a local and regional context to spur change, as described in the paper, has the potential to improve health outcomes. Further research is needed to isolate specific interventions and their knowledge translation outcomes.

Mechanisms of Functional Hypoconnectivity in the Medial Prefrontal Cortex of Mecp2 Null Mice.

Frontal cortical dysfunction is thought to contribute to cognitive and behavioral features of autism spectrum disorders; however, underlying mechanisms are poorly understood. The present study sought to define how loss of Mecp2, the gene mutated in Rett syndrome (RTT), disrupts function in the murine medial prefrontal cortex (mPFC) using acute brain slices and behavioral testing. Compared with wildtype, pyramidal neurons in the Mecp2 null mPFC exhibit significant reductions in excitatory postsynaptic currents, the duration of excitatory UP-states, evoked population activity, and the ratio of NMDA:AMPA currents, as well as an increase in the relative fraction of NR2B currents. These functional changes are associated with reductions in the density of excitatory dendritic spines, the ratio of vesicular glutamate to GABA transporters and GluN1 expression. In contrast to recent reports on circuit defects in other brain regions, we observed no effect of Mecp2 loss on inhibitory synaptic currents or expression of the inhibitory marker parvalbumin. Consistent with mPFC hypofunction, Mecp2 nulls exhibit respiratory dysregulation in response to behavioral arousal. Our data highlight functional hypoconnectivity in the mPFC as a potential substrate for behavioral disruption in RTT and other disorders associated with reduced expression of Mecp2 in frontal cortical regions.

Entrapment via synaptic-like connections between NG2 proteoglycan+ cells and dystrophic axons in the lesion plays a role in regeneration failure after spinal cord injury.

NG2 is purportedly one of the most growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) produced after spinal cord injury. Nonetheless, once the severed axon tips dieback from the lesion core into the penumbra they closely associate with NG2+ cells. We asked if proteoglycans play a role in this tight cell-cell interaction and whether overadhesion upon these cells might participate in regeneration failure in rodents. Studies using varying ratios of CSPGs and adhesion molecules along with chondroitinase ABC, as well as purified adult cord-derived NG2 glia, demonstrate that CSPGs are involved in entrapping neurons. Once dystrophic axons become stabilized upon NG2+ cells, they form synaptic-like connections both in vitro and in vivo. In NG2 knock-out mice, sensory axons in the dorsal columns dieback further than their control counterparts. When axons are double conditioned to enhance their growth potential, some traverse the lesion core and express reduced amounts of synaptic proteins. Our studies suggest that proteoglycan-mediated entrapment upon NG2+ cells is an additional obstacle to CNS axon regeneration.

Preclinical research in Rett syndrome: setting the foundation for translational success.

In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data.

Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment.

Excitatory-inhibitory imbalance has been identified within specific brain microcircuits in models of Rett syndrome (RTT) and other autism spectrum disorders (ASDs). However, macrocircuit dysfunction across the RTT brain as a whole has not been defined. To approach this issue, we mapped expression of the activity-dependent, immediate-early gene product Fos in the brains of wild-type (Wt) and methyl-CpG-binding protein 2 (Mecp2)-null (Null) mice, a model of RTT, before and after the appearance of overt symptoms (3 and 6 weeks of age, respectively). At 6 weeks, Null mice exhibit significantly less Fos labeling than Wt in limbic cortices and subcortical structures, including key nodes in the default mode network. In contrast, Null mice exhibit significantly more Fos labeling than Wt in the hindbrain, most notably in cardiorespiratory regions of the nucleus tractus solitarius (nTS). Using nTS as a model, whole-cell recordings demonstrated that increased Fos expression in Nulls at 6 weeks of age is associated with synaptic hyperexcitability, including increased frequency of spontaneous and miniature EPSCs and increased amplitude of evoked EPSCs in Nulls. No such effect of genotype on Fos or synaptic function was seen at 3 weeks. In the mutant forebrain, reduced Fos expression, as well as abnormal sensorimotor function, were reversed by the NMDA receptor antagonist ketamine. In light of recent findings that the default mode network is hypoactive in autism, our data raise the possibility that hypofunction within this meta-circuit is a shared feature of RTT and other ASDs and is reversible.

End-stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection.

Recipients of haemodialysis for end-stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross-sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fibrosis using Knodell histological activity index. Compared to patients without renal impairment, HCV patients with renal failure were older and more likely to be AA. Patients with renal impairment had lower mean serum transaminases, a higher mean serum alkaline phosphatase levels (all P < 0.0001) and less hepatic necro-inflammation (Knodell histological activity index -I, II and III; P < 0.05) and fibrosis (Knodell histological activity index -IV; P < 0.0001). There were no racial differences in serum liver chemistry and histology scores among patients with renal failure. In a multivariate analysis, younger age, ESRD, AA race and a lower serum alkaline phosphatase were associated with lower odds for advanced liver fibrosis. Thus, HCV patients with ESRD had a lower degree of hepatic inflammation and fibrosis compared to those without renal disease, independent of race.

The reproductive endocrinology and behavior of Vancouver Island marmot (Marmota vancouverensis).

The Vancouver Island marmot (Marmota vancouverensis; VIM) is one of North America's most endangered species with fewer than 150 individuals remaining in the wild. A captive breeding program was established across four facilities in Canada as an insurance population and source of animals for reintroduction to the wild. The purpose of this study was to gather information about the basic reproductive biology and behavior of this species, which is essential to improve captive breeding programs. Regular fecal samples were obtained from adult female (n = 14) and male (n = 10) marmots, 2 years of age and older, over 1-3 breeding seasons (2-3 months duration posthibernation) for steroid hormone analysis. Enzyme immunoassays were validated for quantifying fecal testosterone metabolite concentrations for males, and fecal estrogen and progesterone metabolite concentrations for females. Results indicated that fecal progesterone metabolite concentrations can be used to monitor ovulation and pregnancy. Behavioral monitoring through infrared video surveillance was conducted in four breeding pairs over a 2-year period (n = 7 behavioral profiles). Breeding behaviors correlated strongly with changes in reproductive endocrine profiles. A high frequency of play behavior or "wrestling" was observed in conjunction with breeding activity before an elevation in progesterone metabolite concentrations. Impending parturition was associated with increased aggression and exclusion of the male from the maternal nestbox as well as an increase in nesting activity. Observational data combined with hormonal analysis suggest that female VIMs are induced ovulators and that multiple breeding attempts may be required for ovulation and conception. Gestation appears to be approximately 34 days from peak breeding activity (32 days from estimated ovulation). Fecal testosterone concentrations suggest that testicular activity is seasonal with the reproductive activity occurring immediately posthibernation. Monitoring breeding behavior is a useful means of indicating estrus, conception and pregnancy, which can also be supported by the hormonal analysis of daily fecal samples of individual animals.