Decoding the Reference Letter: Strategies to Reduce Unintentional Gender Bias in Letters of Recommendation.

Introduction: There is a growing body of literature on gender bias in letters of recommendation (LORs) in academic medicine and the negative effect of bias on promotion and career advancement. Thus, increasing knowledge about gender bias and developing skills to mitigate it is important for advancing gender equity in medicine. This workshop aims to provide participants with knowledge about linguistic bias (focused on gender), how to recognize it, and strategies to apply to mitigate it when writing LORs. Methods: We developed an interactive 60-minute workshop for faculty and graduate medical education program directors consisting of didactics, reflection exercises, and group activities. We used a postworkshop survey to evaluate the effectiveness of the workshop. Descriptive statistics were used to analyze Likert-scale questions and a thematic content analysis for open-ended prompts. Results: We presented the workshop four times (two local and two national conferences) with one in-person and one virtual format for each. There were 50 participants who completed a postworkshop survey out of 74 total participants (68% response rate). Ninety-nine percent of participants felt the workshop met its educational objectives, and 100% felt it was a valuable use of their time. Major themes described for intended behavior change included utilization of the gender bias calculator, mindful use and balance of agentic versus communal traits, closer attention to letter length, and dissemination of this knowledge to colleagues. Discussion: This workshop was an effective method for helping participants recognize gender bias when writing LORs and learn strategies to mitigate it.

Our 11-Year Experience With Percutaneous Tibial Nerve Stimulation in Men and Women for the Treatment of Interstitial Cystitis/Bladder Pain Syndrome.

OBJECTIVE: To evaluate the effect of percutaneous tibial nerve stimulation (PTNS) in interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Retrospective chart review was completed for patients with at least 10 weekly treatments of PTNS from January 2010 to October 2021. PTNS success was defined as conversion to PTNS maintenance therapy following 12weeks of PTNS induction therapy. Data were analyzed using GraphPad. RESULTS: Over the 11-year study period, 27 out of 34 patients (mean age 52.9 ± 16.8years; 25 females, 9 males) completed 12weeks of PTNS induction therapy, and 48.1% (13/27) successfully converted to PTNS maintenance therapy. Following 12weeks of PTNS induction therapy, significant improvements were noted in the urgency severity scale (range 0-4: 2.9 ± 1.2 before vs 1.1 ± 1.1 after PTNS, P = .001) and nocturnal urinary frequency (number of voids: 3.3 ± 1.9 before vs 2.2 ± 1.6 after PTNS, P = .041); and nonsignificant improvements were noted in daytime void frequency (hours: 1.5 ± 0.7 before vs 2.0 ± 0.9 after PTNS, P = .090) and the pain domain of the interstitial cystitis symptoms index (question 4, range 0-4: 2.5 ± 1.4 before vs 1.3 ± 1.8 after PTNS, P = .082). CONCLUSION: Our sample size is among the largest sample of PTNS in IC/BPS from a single center. While PTNS achieved nonsignificant improvements in pain and daytime void frequency, significant improvements were observed in urinary urgency and nocturia. PTNS appears to be a plausible option in the multimodal approach to managing IC/BPS.

Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives.

Systemic therapy strategies in the setting of localized and locally advanced renal cell carcinoma have continued to evolve in two directions: (i) as adjuvant therapy (to reduce the risk of recurrence or progression in high-risk localized groups); or (ii) as neoadjuvant therapy as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. In the realm of adjuvant therapy, the results of adjuvant therapy phase III randomized clinical trials have been mixed and contradictory; nevertheless, the findings of the landmark Sunitinib Treatment of Renal Adjuvant Cancer study have led to approval of sunitinib as an adjuvant agent in the USA. In the realm of neoadjuvant therapy, presurgical tumor reduction has been shown in a number of phase II studies utilizing targeted molecular agents and in a recently published small randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for adjuvant and neoadjuvant strategies. The present article reviews the current status and future prospects of adjuvant and neoadjuvant therapy in localized and locally advanced renal cell carcinoma.

Arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by core social impairments. ASD remains poorly understood because of the difficulty in studying disease biology directly in patients and the reliance on mouse models that lack clinically relevant, complex social cognition abilities. We use ethological observations in rhesus macaques to identify male monkeys with naturally occurring low sociality. These monkeys showed differences in specific neuropeptide and kinase signaling pathways compared to socially competent male monkeys. Using a discovery and replication design, we identified arginine vasopressin (AVP) in cerebrospinal fluid (CSF) as a key marker of group differences in monkey sociality; we replicated these findings in an independent monkey cohort. We also confirmed in an additional monkey cohort that AVP concentration in CSF is a stable trait-like measure. Next, we showed in a small pediatric cohort that CSF AVP concentrations were lower in male children with ASD compared to age-matched male children without ASD (but with other medical conditions). We demonstrated that CSF AVP concentration was sufficient to accurately distinguish ASD cases from medical controls. These data suggest that AVP and its signaling pathway warrant consideration in future research studies investigating new targets for diagnostics and drug development in ASD.

Comparison of retroperitoneal and transperitoneal robotic partial nephrectomy for Pentafecta perioperative and renal functional outcomes.

BACKGROUND: We compared quality outcomes between transperitoneal (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN). METHODS: Two-center retrospective analysis of TRPN and RRPN from 10/2009 to 10/2015. Perioperative/renal function outcomes were analyzed. Primary endpoint was Pentafecta, a composite measure of quality [negative margin, no 30-day complication, ischemia time ≤25 min, return of glomerular filtration rate (eGFR) to >90% from baseline at last follow-up, and no chronic kidney disease upstaging]. Multivariable analysis (MVA) for factors associated with lack of optimal outcome was performed. RESULTS: 404 patients (TRPN 263, RRPN 141) were analyzed. Comparing TRPN vs. RRPN, mean tumor size (3.1 vs. 2.9 cm, p = 0.122) and RENAL score (7.4 vs. 7.2, p = 0.503) were similar. Most TRPN were anterior (65.0%) and most RRPN posterior (65.3%, p < 0.001). Operative time (p = 0.001) was less for RRPN. No significant differences between TRPN vs. RRPN were noted for ischemia time (23.1 vs. 22.8 min, p = 0.313), blood loss (p = 0.772), positive margins (p = 0.590), complications (p = 0.537), length of stay (p = 0.296), ΔeGFR (p = 0.246), eGFR recovery to >90% (55.9 vs. 57.4%, p = 0.833), and lack of CKD upstaging (84.0 vs. 87.2%, p = 0.464). Pentafecta rates were not significantly different (TRPN 33.9 vs. RRPN 43.3%, p = 0.526). MVA revealed increasing RENAL score (OR 1.5, p < 0.001) and decreasing baseline eGFR (OR 2.4, p = 0.017) as predictive for lack of Pentafecta. CONCLUSIONS: TRPN and RRPN have similar quality outcomes, though RRPN may offer modest benefit for operative time and have utility in posterior tumors. Association of increasing RENAL score and decreased baseline eGFR with lack of Pentafecta suggests dominant role of non-modifiable factors.

Statin utilization improves oncologic and survival outcomes in patients with dyslipidemia and surgically treated renal cell carcinoma.

BACKGROUND: We evaluated the role of statins in patients who underwent surgery for renal cell carcinoma (RCC) and who had dyslipidemia, as use of statins has been suggested to improve outcomes in RCC. METHODS: Two-center retrospective study of patients with dyslipidemia who underwent surgery for RCC from 7/1995 to 6/2005. Patients were managed by statins or ezetimibe, fibrate agents, or cholestyramine. Analysis was conducted between patients who received statin therapy versus those that did not. Primary outcome was progression-free survival (PFS). Secondary outcomes were cancer-specific (CSS) and overall survival (OS). Multivariable analysis was performed to identify risk factors associated with disease progression. RESULTS: In this study 283 patients were analyzed (180 statin, 103 non-statin, median follow-up 68 months). There were no significant demographic differences. Median duration of antidyslipidemia therapy was similar (statin 31 months vs. non-statin 28 months, P=0.413). Tumor size (statin 5.4 cm vs. non-statin 5.6 cm, P=0.569), stage distribution (P=0.591), histology (P=0.801), and grade (P=0.807) were similar. Kaplan-Meier analysis demonstrated higher 5-yr PFS (91% vs. 70%, P<0.001), CSS (88% vs. 69%, P<0.001), and OS (71% vs. 67%, P=0.025) in statin vs. non-statin patients. Multivariable analysis for factors associated with disease progression found absence of statin therapy (OR 2.41, P<0.001), higher stage (OR 2.01-3.86 P<0.001), and higher grade tumors (OR 2.07, P=0.006) to be predictive. CONCLUSIONS: In RCC patients with dyslipidemia, statin use was associated with improved survival outcomes, and was an independent predictor of PFS. Further investigations are requisite to determine utility of statins in RCC patients.

Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome).

PURPOSE: To describe the frequency and characteristics of developmental regression in a sample of 50 patients with Phelan McDermid Syndrome (PMS) and investigate the possibility of association between regression, epilepsy, and electroencephalogram (EEG) abnormalities and deletion size. METHODS: The Autism Diagnostic Interview-Revised (ADI-R) was used to evaluate regression in patients with a confirmed diagnosis of PMS. Information on seizure history and EEGs was obtained from medical record review. Deletion size was determined by DNA microarray. RESULTS: A history of regression at any age was present in 43% of all patients. Among those exhibiting regression, 67% had onset after the age of 30 months, affecting primarily motor and self-help skills. In 63% of all patients there was a history of seizures and a history of abnormal EEG was also present in 71%. No significant associations were found between regression and seizures or EEG abnormalities. Deletion size was significantly associated with EEG abnormalities, but not with regression or seizures. CONCLUSION: This study found a high rate of regression in PMS. In contrast to regression in autism, that often occurs earlier in development and affects language and social skills, we found regression in PMS most frequently has an onset in mid-childhood, affecting motor and self-help skills. We also found high rates of seizures and abnormal EEGs in patients with PMS. However, a history of abnormal EEG and seizures was not associated with an increased risk of regression. Larger deletion sizes were found to be significantly associated with a history of abnormal EEG.

Comparison of laparoendoscopic single-site (LESS) and multiport laparoscopic radical nephrectomy for clinical T1b and T2a renal masses.

BACKGROUND: The aim of this study was to compare outcomes of laparoendoscopic single-site surgery (LESS) and multiport laparoscopic (MPL) radical nephrectomy (RN) for clinical T1b/T2a renal masses, as concerns continue regarding suitability and benefit of LESS for larger renal masses. METHODS: Retrospective single-surgeon comparison of LESS- and MPL-RN between 7/2005 and 11/2014. Sixty-three patients underwent LESS-RN (44 cT1b/19 cT2a); 133 underwent MPL (83 cT1b/50 cT2a). All patients were managed with a standardized care pathway. Primary outcome was length of hospital stay (LOS). Secondary outcomes included operative time, estimated blood loss (EBL), complications, discharge pain score (visual analog pain, VAP), narcotic requirement (morphine equivalents, MSO4eq). RESULTS: 130/133 MPL and 62/63 LESS were successfully performed. For MPL and LESS groups: mean tumor diameter (cm) for cT1b was 5.3 vs. 5.4 (P=0.689); and for cT2a was 8.2 vs. 8.3 (P=0.728); mean OR time (min) was 126.3 vs. 132.7 (P=0.314); mean EBL (mL) was 139.5 vs.127.8 (P=0.49). No significant differences in complications were noted (P=0.781). LESS was associated with significant reductions in LOS (2.14 vs. 2.45 days, P=0.043), discharge VAP (1.3 vs. 2.2, P<0.001), and narcotic use (5.9 vs. 10.7 MSO4eq, P<0.001). CONCLUSIONS: LESS is comparable to MPL-RN for cT1b and T2a renal tumors in terms of perioperative parameters and may confer benefit with respect to LOS and analgesic requirement.

Corrigendum to "Collision Tumor With Renal Cell Carcinoma and Plasmacytoma: Further Evidence of a Renal Cell and Plasma Cell Neoplasm Relationship?" [Urology Case Reports 6 (2017) 50-52].

[This corrects the article DOI: 10.1016/j.eucr.2016.03.005.].

Impact of tumor histology and grade on treatment success of percutaneous renal cryoablation.

BACKGROUND: We analyzed oncological outcomes in patients who underwent percutaneous renal cryoablation (PRC) with documented renal cell carcinoma (RCC) by perioperative biopsy. METHODS: Multicenter retrospective analysis of 153 patients [median follow-up 48 months] who underwent PRC from 09/2005 to 08/2014 was performed. We divided the cohort into patients who developed recurrence versus no recurrence. Kaplan-Meier analyses examined recurrence-free survival (RFS) according to grade and histology. Multivariable analysis (MVA) was performed to identify factors associated with tumor recurrence. RESULTS: One hundred and fifty-three patients were analyzed [18 patients (11.8 %) with recurrence and 135 (88.2 %) patients without recurrence]. There were no differences between the groups with respect to demographics, RENAL score, and number of probes utilized. Recurrence group had larger tumor size (3.1 vs. 2.4 cm; p = 0.011), upper pole tumor location (p = 0.016), and greater proportions of high-grade tumor (33 vs. 0.7 %; p < 0.001) and clear cell histology (77.8 vs. 45.9 %; p = 0.011). Four-year RFS was 100 versus 80 % for grade 1 versus grade 2/3 tumors (p = 0.0002), and 97 versus 88 % for other RCC versus clear cell RCC (p = 0.07). MVA demonstrated tumor size >3 cm (OR 2.46; p = 0.019), clear cell histology (OR 2.12; p = 0.027), and high tumor grade (OR 2.33, p < 0.001) as independent risk factors associated with tumor recurrence. CONCLUSIONS: Association of higher grade and clear cell histology with recurrence and progression suggests need for increased emphasis on preoperative risk stratification by biopsy, with grade 1 and non-clear cell RCC being associated with improved treatment success than higher grade and clear cell RCC.

Gastrointestinal tract access for urological natural orifice transluminal endoscopic surgery.

We conducted a literature review of natural orifice transluminal endoscopic surgery (NOTES), focusing on urologic procedures with gastrointestinal tract access, to update on the development of this novel surgical approach. As part of the methods, a comprehensive electronic literature search for NOTES was conducted using PubMed and Cochrane Library from March 2002 to February 2016 for papers reporting urologic procedures performed utilizing gastrointestinal tract access. A total of 11 peer-reviewed studies examining utility of gastrointestinal access for NOTES urologic procedures were noted, with the first report in 2007. The procedures reported in the studies were total/radical nephrectomy, partial nephrectomy, adrenalectomy, and prostatectomy. The transgastric approach was identified in five studies examining total/radical nephrectomy (n = 2), partial nephrectomy (n = 1), partial cystectomy (n = 1), and adrenalectomy (n = 1). Six studies evaluated transrectal approach for NOTES, describing total/radical nephrectomy (n = 3), partial nephrectomy (n = 1), robotic nephrectomy with adrenalectomy (n = 1) and prostatectomy (n = 1). Feasibility was reported in all studies. Most studies were preclinical and acute, and limited by concerns regarding restricted instrumentation and infection risk. We concluded that gastrointestinal access for urologic NOTES demonstrates promise as described by outlined feasibility studies in preclinical models. Nonetheless, clinical application awaits further advancements in surgical technology and concerns regarding infectious potential.

Collision Tumor With Renal Cell Carcinoma and Plasmacytoma: Further Evidence of a Renal Cell and Plasma Cell Neoplasm Relationship?

Renal solitary extramedullary plasmacytomas belong to a group of plasma cell neoplasms, which generally have been associated with renal cell carcinoma. We present a case report of a patient with collision tumor histology of extramedullary plasmacytoma and clear cell renal cell carcinoma, the first in the known literature. Standard work-up for a plasma cell neoplasm was conducted and the mass was resected. The patient remains disease-free at 28 months post-surgery. The report calls into question pre-surgical renal mass biopsy protocol and suggests a relationship between renal cell carcinoma and plasma cell neoplasms.

A proton spectroscopy study of white matter in children with autism.

White matter abnormalities have been described in autism spectrum disorder (ASD) with mounting evidence implicating these alterations in the pathophysiology of the aberrant connectivity reported in this disorder. The goal of this investigation is to further examine white matter structure in ASD using proton magnetic resonance spectroscopy ((1)H MRS). Multi-voxel, short echo-time in vivo(1)H MRS data were collected from 17 male children with ASD and 17 healthy age- and gender-matched controls. Key (1)H MRS metabolite ratios relative to phosphocreatine plus creatine were obtained from four different right and left white matter regions. Significantly lower N-acetylaspartate/creatine ratios were found in the anterior white matter regions of the ASD group when compared to controls. These findings reflect impairment in neuroaxonal white matter tissue and shed light on the neurobiologic underpinnings of white matter abnormalities in ASD by implicating an alteration in myelin and/or axonal development in this disorder.

Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.

Brain arginine vasopressin (AVP) critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD). Since blood measures (which are far easier to obtain than brain measures) of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28) undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed between children with ASD (N = 57), their ASD discordant siblings (N = 47), and neurotypical controls (N = 55); and 2) predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP concentrations can be used: 1) as a surrogate for brain AVP activity in humans; and 2) as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.

Ambient noise causes independent changes in distinct spectro-temporal features of echolocation calls in horseshoe bats.

One of the most efficient mechanisms to optimize signal-to-noise ratios is the Lombard effect - an involuntary rise in call amplitude due to ambient noise. It is often accompanied by changes in the spectro-temporal composition of calls. We examined the effects of broadband-filtered noise on the spectro-temporal composition of horseshoe bat echolocation calls, which consist of a constant-frequency component and initial and terminal frequency-modulated components. We found that the frequency-modulated components became larger for almost all noise conditions, whereas the bandwidth of the constant-frequency component increased only when broadband-filtered noise was centered on or above the calls' dominant or fundamental frequency. This indicates that ambient noise independently modifies the associated acoustic parameters of the Lombard effect, such as spectro-temporal features, and could significantly affect the bat's ability to detect and locate targets. Our findings may be of significance in evaluating the impact of environmental noise on echolocation behavior in bats.

Ambient noise induces independent shifts in call frequency and amplitude within the Lombard effect in echolocating bats.

The Lombard effect, an involuntary rise in call amplitude in response to masking ambient noise, represents one of the most efficient mechanisms to optimize signal-to-noise ratio. The Lombard effect occurs in birds and mammals, including humans, and is often associated with several other vocal changes, such as call frequency and duration. Most studies, however, have focused on noise-dependent changes in call amplitude. It is therefore still largely unknown how the adaptive changes in call amplitude relate to associated vocal changes such as frequency shifts, how the underlying mechanisms are linked, and if auditory feedback from the changing vocal output is needed. Here, we examined the Lombard effect and the associated changes in call frequency in a highly vocal mammal, echolocating horseshoe bats. We analyzed how bandpass-filtered noise (BFN; bandwidth 20 kHz) affected their echolocation behavior when BFN was centered on different frequencies within their hearing range. Call amplitudes increased only when BFN was centered on the dominant frequency component of the bats' calls. In contrast, call frequencies increased for all but one BFN center frequency tested. Both amplitude and frequency rises were extremely fast and occurred in the first call uttered after noise onset, suggesting that no auditory feedback was required. The different effects that varying the BFN center frequency had on amplitude and frequency rises indicate different neural circuits and/or mechanisms underlying these changes.

Behavioural and neurobiological implications of linear and non-linear features in larynx phonations of horseshoe bats.

Mammalian vocalizations exhibit large variations in their spectrotemporal features, although it is still largely unknown which result from intrinsic biomechanical properties of the larynx and which are under direct neuromuscular control. Here we show that mere changes in laryngeal air flow yield several non-linear effects on sound production, in an isolated larynx preparation from horseshoe bats. Most notably, there are sudden jumps between two frequency bands used for either echolocation or communication in natural vocalizations. These jumps resemble changes in 'registers' as in yodelling. In contrast, simulated contractions of the main larynx muscle produce linear frequency changes, but are limited to echolocation or communication frequencies. Only by combining non-linear and linear properties can this larynx, therefore, produce sounds covering the entire frequency range of natural calls. This may give behavioural meaning to yodelling-like vocal behaviour and reshape our thinking about how the brain controls the multitude of spectral vocal features in mammals.

Postnatal development in Andersen's leaf-nosed bat Hipposideros pomona: flight, wing shape, and wing bone lengths.

Postnatal changes in flight development, wing shape and wing bone lengths of 56 marked neonate Hipposideros pomona were investigated under natural conditions in southwest China. Flight experiments showed that pups began to flutter with a short horizontal displacement at 10 days and first took flight at 19 days, with most achieving sustained flight at 1 month old. Analysis of covariance on wingspan, wing area, and the other seven wing characteristics between 'pre-flight' and 'post-volancy' periods supports the hypothesis that growth had one 'pre-flight' trajectory and a different 'post-volancy' trajectory in bats. Wingspan, handwing length and area, armwing length and area, and total wing area increased linearly until the age of first flight, after which the growth rates decreased (all P < 0.001). Wing loading declined linearly until day 19 before ultimately decreasing to adult levels (P < 0.001). Additionally, the relationship of different pairwise combinations of bony components composing span-wise length and chord-wise length was evaluated to test the hypothesis that compensatory growth of wing bones in H. pomona occurred in both 'pre-flight' and 'post-volancy' periods. The frequency of short-long and long-short pairs was significantly greater than that of short-short, long-long pairs in most pairs of bone elements in adults. The results indicate that a bone 'shorter than expected' would be compensated by a bone or bones 'longer than expected', suggesting compensatory growth in H. pomona. The pairwise comparisons conducted in adults were also performed in young bats during 'pre-flight' and 'post-volancy' periods, demonstrating that compensatory growth occurred throughout postnatal ontogeny.

Pleistocene glacial cycle effects on the phylogeography of the Chinese endemic bat species, Myotis davidii.

BACKGROUND: Global climatic oscillations, glaciation cycles and the unique geographic topology of China have profoundly influenced species population distributions. In most species, contemporary distributions of populations cannot be fully understood, except in a historical context. Complex patterns of Pleistocene glaciations, as well as other physiographic changes have influenced the distribution of bat species in China. Until this study, there had been no phylogeographical research on Myotis davidii, an endemic Chinese bat. We used a combination of nuclear and mitochondrial DNA markers to investigate genetic diversity, population structure, and the demographic history of M. davidii. In particular, we compared patterns of genetic variation to glacial oscillations, topography, and environmental variation during the Pleistocene in an effort to explain current distributions in light of these historical processes. RESULTS: M. davidii comprises three lineages (MEP, SWP and SH) based on the results of molecular variance analysis (AMOVA) and phylogenetic analyses. The results of a STRUCTURE analysis reveal multi-hierarchical population structure in M. davidii. Nuclear and mitochondrial genetic markers reveal different levels of gene flow among populations. In the case of mtDNA, populations adhere to an isolation-by-distance model, whereas the individual assignment test reveals considerable gene flow between populations. MDIV analysis indicate that the split of the MEP and SWP/SH lineages, and from the SWP and SH lineages were at 201 ka BP and 158 ka BP, respectively. The results of a mismatch distribution analysis and neutrality tests indicate a population expansion event at 79.17 ka BP and 69.12 ka BP in MEP and SWP, respectively. CONCLUSIONS: The complex demographic history, discontinuous extant distribution of haplotypes, and multiple-hierarchy population structure of M. davidii appear associated with climatic oscillations, topography and eco-environmental variation of China. Additionally, the three regions are genetically differentiated from one another in the entire sample set. The degree of genetic differentiation, based on the analysis of mtDNA and nDNA, suggests a male-mediated gene flow among populations. Refuges were in the MEP, SH and the lower elevations of SWP regions. This study also provides insights for conservation management units (MEP, SWP and SH).

Phylogeography and population genetic structure of the great leaf-nosed bat (Hipposideros armiger) in China.

The geographical patterns of the genetic structure of Hipposideros armiger in China were assessed by analyzing sequence variation in the mitochondrial DNA control region. Analysis of molecular variance revealed a very strong genetic structure among 5 regions in H. armiger. A neighbor-joining tree, haplotype network construction by TCS and multidimensional scaling plots all showed significant geographic differentiation among 5 regions. The high genetic structure detected in H. armiger could be a consequence of poor dispersal ability, local adaptation, or marked female philopatry. The lack of genetic structure among 3 regions separated by the Gaoligong Range and the Qiongzhou Strait could be due to incomplete lineage sorting. Our estimated times of divergence for H. armiger populations suggested a relatively recent split. The S Yunnan population with the highest genetic diversity and the Hainan population with the lowest genetic diversity should be equally given priority for conservation. Although H. armiger has been shown to carry viruses implicated in human disease, we find little evidence for population mixing. We thus suggest minimizing disturbance to bats' roosting caves for minimizing the potential risk of virus transmission.