Increasing equity in science requires better ethics training: A course by trainees, for trainees.

Despite the profound impacts of scientific research, few scientists have received the necessary training to productively discuss the ethical and societal implications of their work. To address this critical gap, we-a group of predominantly human genetics trainees-developed a course on genetics, ethics, and society. We intend for this course to serve as a template for other institutions and scientific disciplines. Our curriculum positions human genetics within its historical and societal context and encourages students to evaluate how societal norms and structures impact the conduct of scientific research. We demonstrate the utility of this course via surveys of enrolled students and provide resources and strategies for others hoping to teach a similar course. We conclude by arguing that if we are to work toward rectifying the inequities and injustices produced by our field, we must first learn to view our own research as impacting and being impacted by society.

Modeling the effects of consanguinity on autosomal and X-chromosomal runs of homozygosity and identity-by-descent sharing.

Runs of homozygosity (ROH) and identity-by-descent (IBD) sharing can be studied in diploid coalescent models by noting that ROH and IBD-sharing at a genomic site are predicted to be inversely related to coalescence times-which in turn can be mathematically obtained in terms of parameters describing consanguinity rates. Comparing autosomal and X-chromosomal coalescent models, we consider ROH and IBD-sharing in relation to consanguinity that proceeds via multiple forms of first-cousin mating. We predict that across populations with different levels of consanguinity, (1) in a manner that is qualitatively parallel to the increase of autosomal IBD-sharing with autosomal ROH, X-chromosomal IBD-sharing increases with X-chromosomal ROH, owing to the dependence of both quantities on consanguinity levels; (2) even in the absence of consanguinity, X-chromosomal ROH and IBD-sharing levels exceed corresponding values for the autosomes, owing to the smaller population size and lower coalescence time for the X chromosome than for autosomes; (3) with matrilateral consanguinity, the relative increase in ROH and IBD-sharing on the X chromosome compared to the autosomes is greater than in the absence of consanguinity. Examining genome-wide SNPs in human populations for which consanguinity levels have been estimated, we find that autosomal and X-chromosomal ROH and IBD-sharing levels generally accord with the predictions. We find that each 1% increase in autosomal ROH is associated with an increase of 2.1% in X-chromosomal ROH, and each 1% increase in autosomal IBD-sharing is associated with an increase of 1.6% in X-chromosomal IBD-sharing. For each calculation, particularly for ROH, the estimate is reasonably close to the increase of 2% predicted by the population-size difference between autosomes and X chromosomes. The results support the utility of coalescent models for understanding patterns of genomic sharing and their dependence on sex-biased processes.

Genomic and demographic processes differentially influence genetic variation across the human X chromosome.

Many forces influence genetic variation across the genome including mutation, recombination, selection, and demography. Increased mutation and recombination both lead to increases in genetic diversity in a region-specific manner, while complex demographic patterns shape patterns of diversity on a more global scale. While these processes act across the entire genome, the X chromosome is particularly interesting because it contains several distinct regions that are subject to different combinations and strengths of these forces: the pseudoautosomal regions (PARs) and the X-transposed region (XTR). The X chromosome thus can serve as a unique model for studying how genetic and demographic forces act in different contexts to shape patterns of observed variation. We therefore sought to explore diversity, divergence, and linkage disequilibrium in each region of the X chromosome using genomic data from 26 human populations. Across populations, we find that both diversity and substitution rate are consistently elevated in PAR1 and the XTR compared to the rest of the X chromosome. In contrast, linkage disequilibrium is lowest in PAR1, consistent with the high recombination rate in this region, and highest in the region of the X chromosome that does not recombine in males. However, linkage disequilibrium in the XTR is intermediate between PAR1 and the autosomes, and much lower than the non-recombining X. Finally, in addition to these global patterns, we also observed variation in ratios of X versus autosomal diversity consistent with population-specific evolutionary history as well. While our results were generally consistent with previous work, two unexpected observations emerged. First, our results suggest that the XTR does not behave like the rest of the recombining X and may need to be evaluated separately in future studies. Second, the different regions of the X chromosome appear to exhibit unique patterns of linked selection across different human populations. Together, our results highlight profound regional differences across the X chromosome, simultaneously making it an ideal system for exploring the action of evolutionary forces as well as necessitating its careful consideration and treatment in genomic analyses.

Atraumatic Exertional Compartment Syndrome of the Medial Foot: Case Report.

Introduction: Acute compartment syndrome is a surgical emergency that is mainly diagnosed clinically. Acute exertional compartment syndrome of the medial compartment of the foot is a rare condition most often result from strenuous exercise. Early diagnosis is most often a clinical examination, however, laboratory and magnetic resonance imaging (MRI) can assist in the diagnosis if clinician uncertainty persists. We present a case report of acute exertional compartment syndrome of the medial compartment of the foot after physical activity. Case Report: A 28-year-old male presents to the emergency department the day after playing basketball, with severe atraumatic medial foot pain. Clinical examination demonstrated tenderness and swelling over the medial arch of the foot. Creatine phosphokinase (CPK) results at 9500 international units. MRI demonstrated fusiform edema of the abductor hallucis. Subsequent fasciotomy revealed protruding muscle during fascial incision and relieved the patient of their pain. Return to surgery 48 h after initial fasciotomy revealed gray discoloration and lack of contractility of the muscle tissue. The patient was recovering well at the first post-operative visit, however, was lost to follow-up thereafter. Conclusion: Acute exertional compartment syndrome of the medial compartment of the foot is a rarely reported diagnosis, likely due to a combination of missed diagnosis and underreporting. Laboratory tests for CPK may be elevated, and MRI may be helpful in the diagnosis of this condition. Fasciotomy of the medial compartment of the foot relieved the patient's symptoms, and to our knowledge had a good outcome.

Organization of the human intestine at single-cell resolution.

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.

The effect of subscapularis-specific rehabilitation following total shoulder arthroplasty: a prospective, double-blinded, randomized controlled trial.

BACKGROUND: Patients undergoing a total shoulder arthroplasty (TSA) through a deltopectoral approach will require repair of the subscapularis tendon. There are no universal postoperative guidelines for rehabilitation of the subscapularis specifically. We hypothesize that the addition of a subscapularis-specific regimen will result in improved subscapularis strength and function. METHODS: Adult patients undergoing anatomic TSA for the treatment of primary glenohumeral osteoarthritis were included. Patients were randomized into either the traditional rehabilitation (TR) control group or the subscapularis rehabilitation (SR) group, which consisted of the traditional therapy along with early and additional subscapularis exercises. Baseline demographics, patient-reported outcome measures (PROMs), range of motion (ROM), provocative tests, and subscapularis strength using a handheld dynamometer were measured preoperatively at the initial clinic visit (ICV) as well as 3 months, 6 months, and 1 year postoperatively. The primary outcome of interest was a comparison of subscapularis strength between cohorts relative to preoperative baseline, whereas secondary outcomes were functional, ROM, and PROMs. RESULTS: Sixty-six patients were included in the final analysis (32 TR vs. 34 SR). There were no statistically significant differences between cohorts at the ICV with regard to demographics, baseline subscapularis strength, functional testing, or PROMs. All postoperative time points demonstrated similar subscapularis strength testing between TR and SR groups (P > .05). Additionally, peak and average subscapularis strength testing at 3, 6, and 12 months postoperatively were similar to baseline ICV testing in both groups. Both groups demonstrated improvements across several provocative tests, ROM, and PROM outcome metrics at every postoperative time point as compared to baseline ICV values (P < .05). CONCLUSIONS: Patients undergoing anatomic TSA return to baseline internal rotation strength by 3 months postoperatively and demonstrate significant improvements in function, ROM, and several patient-reported outcome measures. The addition of early and focused subscapularis strengthening exercises does not appear to significantly impact any outcomes when compared to traditional rehabilitation programs.

High Return to Play Rate and Diminished Career Longevity are Seen Following Arthroscopic Shoulder Labral Repair in Major League Baseball Players.

Purpose: To evaluate the impact of arthroscopic shoulder labral repair, not related to instability, on return to play (RTP), return to prior performance (RTPP), game utilization, and performance in Major League Baseball (MLB) pitchers and positional players. Methods: A retrospective review of all MLB athletes who underwent arthroscopic shoulder labrum repair from 2002 to 2020 was performed. Players with a history of instability events were excluded. A 2:1 control cohort of healthy MLB players were matched to the operative cohort by age, years of experience, position, height, and body mass index (BMI). Player demographics, game utilization, and performance metrics were collected for all players. Results: Twenty-six of 39 MLB pitchers (66%) and 18 of 25 (72%) positional players, who underwent arthroscopic shoulder labral repair RTP, with 46.2% of pitchers and 72% of positional players successfully RTP. At one season postsurgery, pitchers and positional players experienced a significant reduction in games played compared to their one season preinjury (44.7 ± 29.3 vs 109.5 ± 73.2 games; P < .001 and 75.7 ± 47.1 vs 98.0 ± 50.7 games; P = .04). When compared with matched controls at one season postinjury, pitchers had significantly fewer runs allowed per 9 innings (5.8 ± 2.0 vs 4.3 ± 1.4; P = .0061) and walk and hits per inning pitched (WHIP) (1.5 ± 0.3 vs 1.3 ± 0.2; P = .0035), while positional players had worse on-base percentage (0.3 ± 0.1 vs 0.3 ± 0.1; P = .0116). Both pitchers and positional players experienced significantly shorter career lengths after surgery (P = .002) when compared to controls. Conclusions: Following arthroscopic shoulder labral surgery, most MLB pitchers and positional players were able to RTP successfully but experienced shorter careers thereafter. These players also experienced declines in game utilization and performance one season after surgery but were able to return to baseline at 3 seasons after surgery. Level of Evidence: Level III, retrospective case control.

Patient factors influencing the choice of opioid versus non-opioid postoperative analgesia following common sports procedures: a prospective survey study.

Purpose: Despite established opioid-free protocols for postoperative analgesia after common orthopaedic sports procedures, many patients continue to request opioids postoperatively. The purpose of this study was to elucidate patient factors influencing preferences for opioid versus nonopioid postoperative analgesia. Methods: Patients (age >/ = 15) without a history of a documented chronic pain disorder who were scheduled for one of ten sports procedure types from August 2020 to May 2021 were eligible for inclusion. Patients were excluded if undergoing revision surgery, had concomitant injuries, had opioids use >3 months preoperatively, or unable to read English. Recruitment ended after 100 patients enrolled. At the patients' preoperative visit, patients were administered a written survey assessing pain medication preferences. Participants completed the Opioid Risk Tool survey, as well as Visual Analog Scale and Patient-Reported Outcome Measurement Information System surveys. Results: One hundred patients participated in the study. Forty-two patients preferred opioids versus 58 patients preferring nonopioid postoperative analgesia. Patients preferring opiates were more likely to have had previous surgery (90.2% vs. 69.6%, p = 0.023) with post-operative pain managed with opiates (87.5% vs 55.4%, p = 0.003), higher preoperative Visual Analog Scale score (6±3.5 vs. 3±2, p < 0.001), reported post-operative pain as a reason for opioids preference (88.1% vs 20.0%, p < 0.001), and were less concerned about addiction (4.8% vs. 45.5%, p < 0.001) and side effects (11.9% vs. 52.7%, p < 0.001). For every unit increase in Visual Analog Scale score, the odds of preferring opioid pain control increased 1.41 times. Conclusions: Patients with a history of prior surgery utilizing opioid pain control, higher Visual Analog Scale scores preoperatively, and concern for inadequately managed postoperative pain were more likely to prefer opioid pain control following common orthopaedic sports procedures. Patients may benefit from increased preoperative education about opioid risks and the role of multimodal pain management regimens.

A rarefaction approach for measuring population differences in rare and common variation.

In studying allele-frequency variation across populations, it is often convenient to classify an allelic type as "rare," with nonzero frequency less than or equal to a specified threshold, "common," with a frequency above the threshold, or entirely unobserved in a population. When sample sizes differ across populations, however, especially if the threshold separating "rare" and "common" corresponds to a small number of observed copies of an allelic type, discreteness effects can lead a sample from one population to possess substantially more rare allelic types than a sample from another population, even if the two populations have extremely similar underlying allele-frequency distributions across loci. We introduce a rarefaction-based sample-size correction for use in comparing rare and common variation across multiple populations whose sample sizes potentially differ. We use our approach to examine rare and common variation in worldwide human populations, finding that the sample-size correction introduces subtle differences relative to analyses that use the full available sample sizes. We introduce several ways in which the rarefaction approach can be applied: we explore the dependence of allele classifications on subsample sizes, we permit more than two classes of allelic types of nonzero frequency, and we analyze rare and common variation in sliding windows along the genome. The results can assist in clarifying similarities and differences in allele-frequency patterns across populations.

Survey of blood flow restriction therapy for rehabilitation in Sports Medicine patients.

Background: Blood flow restriction (BFR) therapy has demonstrated benefits across a spectrum of musculoskeletal injuries, including improved strength, endurance, function, and reduction in pain perception. There is, however, no standardized application of BFR therapy among orthopaedic surgeons within the United States (US). Hypothesis: The indication and protocol for BFR therapy vary significantly across providers in the US. Methods: An online survey of 21 multiple-choice questions was sent to 3,281 surgeons listed on a large orthopaedic registry. A cross-sectional study was performed on all surgeons who successfully completed the questionnaire. Surgeons were queried on current or planned use of BFR, indications, contraindications, and peri-operative and non-operative management of sports-related injuries. Results: Overall, 250 physicians completed the survey, with 149 (59.8%) reporting current BFR use and 75.2% initiating use in the last 1-5 years. Most protocols (78.8%) utilize the modality 2-3 times per week while 15.9% use it only once weekly. Anterior cruciate ligament reconstruction (ACLR) rehabilitation was the most reported indication for initiating BFR therapy (95.7%) along with medial patellofemoral ligament reconstruction (70.2%), multiligamentous knee reconstruction (68.8%), meniscus repair (62.4%), collateral ligament reconstruction (50.4%), Achilles tendon repairs (30.5%), and meniscectomy (27%). Only 36.5% reported using BFR after upper extremity procedures, such as distal biceps repair (19.7%), ulnar collateral ligament elbow reconstruction (17%), rotator cuff (16.8%), and shoulder labrum repair (15.3%). For non-operative injuries, 65.8% of surgeons utilized BFR. Of those not currently using BFR therapy, 33.3% intended to implement its use in the future. Conclusion: BFR therapy has increased in popularity with most physicians implementing its use in the last 5 years. BFR was commonly utilized after ACLR. Clinical relevance: BFR allows light-load resistance to simulate high-intensity resistance training. This study describes US orthopaedic surgeons' common practice patterns and patient populations that utilize BFR therapy.

Limiting distribution of X-chromosomal coalescence times under first-cousin consanguineous mating.

By providing additional opportunities for coalescence within families, the presence of consanguineous unions in a population reduces coalescence times relative to non-consanguineous populations. First-cousin consanguinity can take one of six forms differing in the configuration of sexes in the pedigree of the male and female cousins who join in a consanguineous union: patrilateral parallel, patrilateral cross, matrilateral parallel, matrilateral cross, bilateral parallel, and bilateral cross. Considering populations with each of the six types of first-cousin consanguinity individually and a population with a mixture of the four unilateral types, we examine coalescent models of consanguinity. We previously computed, for first-cousin consanguinity models, the mean coalescence time for X-chromosomal loci and the limiting distribution of coalescence times for autosomal loci. Here, we use the separation-of-time-scales approach to obtain the limiting distribution of coalescence times for X-chromosomal loci. This limiting distribution has an instantaneous coalescence probability that depends on the probability that a union is consanguineous; lineages that do not coalesce instantaneously coalesce according to an exponential distribution. We study the effects on the coalescence time distribution of the type of first-cousin consanguinity, showing that patrilateral-parallel and patrilateral-cross consanguinity have no effect on X-chromosomal coalescence time distributions and that matrilateral-parallel consanguinity decreases coalescence times to a greater extent than does matrilateral-cross consanguinity.

Reduced Career Longevity but Return to Baseline Performance After Arthroscopic Shoulder Labral Repair in National Hockey League Players.

Purpose: To investigate the impact of arthroscopic shoulder labral repair without shoulder instability on career longevity, game use, and performance in National Hockey League (NHL) athletes. Methods: A retrospective review of all NHL players who underwent arthroscopic shoulder labral repair from 2004 to 2020 was performed. A 2:1 matched control group was used for comparison. Controls were matched by age, body mass index, position, and experience prior to the index year. Demographic characteristics, game use, and performance metrics were collected for all athletes. Statistical analysis examined game use and performance both at 1-year and 3-year follow-up compared with one season before injury. Results: Twenty-nine players who underwent arthroscopic shoulder labral surgery returned to play (100%) and were matched with 55 control players. The operative cohort experienced shorter careers compared with controls (4.4 ± 3.1 vs 6.0 ± 3.6 seasons, P < .05). After one season, injured players experienced significant reductions in goals per 60 (0.6 ± 0.4 vs 0.8 ± 0.5, P = .013), points per 60 (1.5 ± 0.9 vs 2.0 ± 0.9, P = .001), and shooting percentage, (8.5 ± 5.8 vs 10.5 ± 5.2, P = .02) compared with the year prior. The reduction in goals (0.6 ± 0.4 vs 0.8 ± 0.5, P = .01) and shooting % (8.5 ± 4.7 vs 10.5 ± 5.2, P = .04) persisted at 3 years. Compared with controls, the surgical group experienced significant reductions at one season postindex in percentage of goals, assists, points per 60, and shooting percentage. Only the reduction in goals per 60 persisted at 3 seasons postindex. Conclusions: Following return to play after arthroscopic shoulder labral repair, NHL players demonstrated reduced career longevity compared with healthy controls. Players exhibited significant reductions in game use and performance at one season after injury but returned closer to baseline after 3 seasons. Level of Evidence: Level III; retrospective case control.

The effect of consanguinity on coalescence times on the X chromosome.

Consanguineous unions increase the frequency at which identical genomic segments are inherited along separate paths of descent, decreasing coalescence times for pairs of alleles drawn from an individual who is the offspring of a consanguineous pair. For an autosomal locus, it has recently been shown that the mean time to the most recent common ancestor (TMRCA) for two alleles in the same individual and the mean TMRCA for two alleles in two separate individuals both decrease with increasing consanguinity in a population. Here, we extend this analysis to the X chromosome, considering X-chromosomal coalescence times under a coalescent model with diploid, male-female mating pairs. We examine four possible first-cousin mating schemes that are equivalent in their effects on autosomes, but that have differing effects on the X chromosome: patrilateral-parallel, patrilateral-cross, matrilateral-parallel, and matrilateral-cross. In each mating model, we calculate mean TMRCA for X-chromosomal alleles sampled either within or between individuals. We describe a consanguinity effect on X-chromosomal TMRCA that differs from the autosomal pattern under matrilateral but not under patrilateral first-cousin mating. For matrilateral first cousins, the effect of consanguinity in reducing TMRCA is stronger on the X chromosome than on the autosomes, with an increased effect of parallel-cousin mating compared to cross-cousin mating. The theoretical computations support the utility of the model in understanding patterns of genomic sharing on the X chromosome.

The impact of sex on gene expression across human tissues.

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.

Ten-year disease progression and mortality rates in men who experience biochemical recurrence versus persistence after radical prostatectomy and undergo salvage radiation therapy: A post-hoc analysis of RTOG 9601 trial data.

PURPOSE: To compare local/metastatic disease progression and overall mortality rates in men with node-negative prostate cancer at radical prostatectomy (RP) that experience biochemical recurrence vs. persistence postoperatively and undergo salvage radiation therapy (sRT). MATERIALS AND METHODS: Data on 760 men who participated in the RTOG 9601 trial were extracted using the NCTN data archive platform. Patients were stratified into biochemical recurrence (nadir-PSA ≤0.4 ng/ml) or persistence (nadir-PSA >0.4 ng/ml) groups, based on the cut-off reported in the original trial. Inverse probability of treatment weighting (IPTW) methodology was utilized to minimize the baseline differences among groups. Competing-risk and Kaplan-Meier analyses estimated the impact of prostate-specific antigen (PSA) persistence vs. recurrence on local and metastatic disease progression and overall-mortality in the IPTW-adjusted model; a 2-sided P < 0.05 was considered significant. RESULTS: All patients received sRT, and about 50% of the patients in either group received concomitant antiandrogen therapy (P = 0.951). The median follow-up was 12 years. After IPTW, the 2 groups were well-matched with standardized mean differences ∼10%. In the IPTW-adjusted cohort, the 10-year local and metastatic disease occurrence rates were 3.2% vs. 1.4% (Gray's P = 0.0001) and 28.6% vs. 10.1% (Gray's P < 0.0001) in patients with persistent vs. recurrent PSA, respectively. Similarly, the 10-year overall-mortality rates were 24.9% vs. 11.9% (Log-rank P = 0.029), respectively. CONCLUSIONS: Patients with biochemical persistence after RP are approximately 2.5 times more likely to experience local/metastatic failure and death, compared to patients with biochemical recurrence after RP, despite equivalent sRT with/without antiandrogen therapy use. These data may facilitate patient counseling and shared treatment selection.

Relationship between serum iohexol clearance, serum SDMA concentration, and serum creatinine concentration in non-azotemic dogs.

BACKGROUND: Serum creatinine and symmetric dimethylarginine (SDMA) are used as surrogate markers of glomerular filtration rate (GFR) in clinical practice. Data pertaining to the correlations between GFR, SDMA, and serum creatinine in client-owned dogs are limited. OBJECTIVES: To describe the relationship between GFR, SDMA, and serum creatinine in a population of client-owned dogs, and to compare clinical utility of SDMA to GFR estimation for detecting pre-azotemic chronic kidney disease. ANIMALS: Medical records of 119 dogs that had GFR estimation performed via serum iohexol clearance between 2012 and 2017. METHODS: Prospective study using archived samples. GFR, SDMA, and serum creatinine results were reviewed and submitting practices contacted for outcome data. All dogs included in the study population were non-azotemic. Correlations between GFR, SDMA, and serum creatinine were determined by regression analysis. Sensitivity, specificity, and positive and negative likelihood ratios of different cutoffs for SDMA and serum creatinine for detecting decreased GFR were calculated, using a 95% confidence interval. RESULTS: Serum creatinine and SDMA were moderately correlated with GFR (R2 = 0.52 and 0.27, respectively, P < .0001) and with each other (R2 = 0.33, P < .0001). SDMA >14 µg/dL was sensitive (90%) but nonspecific (50%) for detecting a ≥40% decrease in GFR. Optimal SDMA concentration cutoff for detecting a ≥40% GFR decrease was >18 µg/dL (sensitivity 90%, specificity 83%). CONCLUSIONS AND CLINICAL IMPORTANCE: In non-azotemic dogs being screened for decreased renal function, using a cutoff of >18 µg/dL rather than >14 µg/dL increases the specificity of SDMA, without compromising sensitivity.

Ancient Rome: A genetic crossroads of Europe and the Mediterranean.

Ancient Rome was the capital of an empire of ~70 million inhabitants, but little is known about the genetics of ancient Romans. Here we present 127 genomes from 29 archaeological sites in and around Rome, spanning the past 12,000 years. We observe two major prehistoric ancestry transitions: one with the introduction of farming and another prior to the Iron Age. By the founding of Rome, the genetic composition of the region approximated that of modern Mediterranean populations. During the Imperial period, Rome's population received net immigration from the Near East, followed by an increase in genetic contributions from Europe. These ancestry shifts mirrored the geopolitical affiliations of Rome and were accompanied by marked interindividual diversity, reflecting gene flow from across the Mediterranean, Europe, and North Africa.

Circularly polarized luminescence of Sm (III) and Eu (III) complexes with chiral ligand (R/S)-BINAPO.

Luminescent lanthanide (III) ions have been exploited for circularly polarized luminescence (CPL) for decades. However, very few of these studies have involved chiral samarium (III) complexes. Complexes are prepared by mixing axial chiral ligands (R/S))-2,2'-bis(diphenylphosphoryl)-1,1'-binaphthyl (BINAPO) with europium and samarium Tris (trifluoromethane sulfonate) (Eu (OTf)3 and Sm (OTf)3 ). Luminescence-based titration shows that the complex formed is Ln((R/S)-BINAPO)2 (OTf)3 , where Ln = Eu or Sm. The CPL spectra are reported for Eu((R/S)-BINAPO)2 (OTf)3 and Sm((R/S)-BINAPO)2 (OTf)3 . The sign of the dissymmetry factors, gem , was dependent upon the chirality of the BINAPO ligand, and the magnitudes were relatively large. Of all of the complexes in this study, Sm((S)-BINAPO)2 (OTf)3 has the largest gem  = 0.272, which is one of the largest recorded for a chiral Sm3+ complex. A theoretical three-dimensional structural model of the complex that is consistent with the experimental observations is developed and refined. This report also shows that (R/S)-BINAPO are the only reported ligands where gem (Sm3+ ) > gem (Eu3+ ).

Genetic Diversity on the Human X Chromosome Does Not Support a Strict Pseudoautosomal Boundary.

Unlike the autosomes, recombination between the X chromosome and the Y chromosome is often thought to be constrained to two small pseudoautosomal regions (PARs) at the tips of each sex chromosome. PAR1 spans the first 2.7 Mb of the proximal arm of the human sex chromosomes, whereas the much smaller PAR2 encompasses the distal 320 kb of the long arm of each sex chromosome. In addition to PAR1 and PAR2, there is a human-specific X-transposed region that was duplicated from the X to the Y chromosome. The X-transposed region is often not excluded from X-specific analyses, unlike the PARs, because it is not thought to routinely recombine. Genetic diversity is expected to be higher in recombining regions than in nonrecombining regions because recombination reduces the effect of linked selection. In this study, we investigated patterns of genetic diversity in noncoding regions across the entire X chromosome of a global sample of 26 unrelated genetic females. We found that genetic diversity in PAR1 is significantly greater than in the nonrecombining regions (nonPARs). However, rather than an abrupt drop in diversity at the pseudoautosomal boundary, there is a gradual reduction in diversity from the recombining through the nonrecombining regions, suggesting that recombination between the human sex chromosomes spans across the currently defined pseudoautosomal boundary. A consequence of recombination spanning this boundary potentially includes increasing the rate of sex-linked disorders (e.g., de la Chapelle) and sex chromosome aneuploidies. In contrast, diversity in PAR2 is not significantly elevated compared to the nonPARs, suggesting that recombination is not obligatory in PAR2. Finally, diversity in the X-transposed region is higher than in the surrounding nonPARs, providing evidence that recombination may occur with some frequency between the X and Y chromosomes in the X-transposed region.