Vocational interests predict educational and career choices, job performance, and career success (Rounds & Su, 2014). Although sex differences in vocational interests have long been observed ...(Thorndike, 1911), an appropriate overall measure has been lacking from the literature. Using a cross-sectional sample of United States residents aged 14 to 63 who completed the Strong Interest Inventory assessment between 2005 and 2014 (N = 1,283,110), I examined sex, age, ethnicity, and year effects on work related interest levels using both multivariate and univariate effect size estimates of individual dimensions (Holland's Realistic, Investigative, Artistic, Social, Enterprising, and Conventional). Men scored higher on Realistic (d = −1.14), Investigative (d = −.32), Enterprising (d = −.22), and Conventional (d = −.23), while women scored higher on Artistic (d = .19) and Social (d = .38), mostly replicating previous univariate findings. Multivariate, overall sex differences were very large (disattenuated Mahalanobis' D = 1.61; 27% overlap). Interest levels were slightly lower and overall sex differences larger in younger samples. Overall sex differences have narrowed slightly for 18-22 year-olds in more recent samples. Generally very small ethnicity effects included relatively higher Investigative and Enterprising scores for Asians, Indians, and Middle Easterners, lower Realistic scores for Blacks and Native Americans, higher Realistic, Artistic, and Social scores for Pacific Islanders, and lower Conventional scores for Whites. Using Prediger's (1982) model, women were more interested in people (d = 1.01) and ideas (d = .18), while men were more interested in things and data. These results, consistent with previous reviews showing large sex differences and small year effects, suggest that large sex differences in work related interests will continue to be observed for decades.
Public Significance Statement
This study of a large, diverse sample of United States residents found that there were large sex differences in work-related interests for all age groups and all ethnicities, and that these differences are likely to persist. Because interests predict major and occupational choices, among other important outcomes, these findings suggest that men and women will continue to experience differing educational and career outcomes.
The anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab is approved by the US Food and Drug Administration for the treatment of microsatellite instability-high (MSI-H) or mismatch ...repair-deficient (dMMR) solid tumors, but the prevalence of MSI-H/dMMR prostate cancer and the clinical utility of immune checkpoint blockade in this disease subset are unknown.
To define the prevalence of MSI-H/dMMR prostate cancer and the clinical benefit of anti-PD-1/programmed cell death 1 ligand 1 (PD-L1) therapy in this molecularly defined population.
In this case series, 1551 tumors from 1346 patients with prostate cancer undergoing treatment at Memorial Sloan Kettering Cancer Center were prospectively analyzed using a targeted sequencing assay from January 1, 2015, through January 31, 2018. Patients had a diagnosis of prostate cancer and consented to tumor molecular profiling when a tumor biopsy was planned or archival tissue was available. For each patient, clinical outcomes were reported, with follow-up until May 31, 2018.
Tumor mutation burden and MSIsensor score, a quantitative measure of MSI, were calculated. Mutational signature analysis and immunohistochemistry for MMR protein expression were performed in select cases.
Among the 1033 patients who had adequate tumor quality for MSIsensor analysis (mean SD age, 65.6 9.3 years), 32 (3.1%) had MSI-H/dMMR prostate cancer. Twenty-three of 1033 patients (2.2%) had tumors with high MSIsensor scores, and an additional 9 had indeterminate scores with evidence of dMMR. Seven of the 32 MSI-H/dMMR patients (21.9%) had a pathogenic germline mutation in a Lynch syndrome-associated gene. Six patients had more than 1 tumor analyzed, 2 of whom displayed an acquired MSI-H phenotype later in their disease course. Eleven patients with MSI-H/dMMR castration-resistant prostate cancer received anti-PD-1/PD-L1 therapy. Six of these (54.5%) had a greater than 50% decline in prostate-specific antigen levels, 4 of whom had radiographic responses. As of May 2018, 5 of the 6 responders (5 of 11 total 45.5%) were still on therapy for as long as 89 weeks.
The MSI-H/dMMR molecular phenotype is uncommon yet therapeutically meaningful in prostate cancer and can be somatically acquired during disease evolution. Given the potential for durable responses to anti-PD-1/PD-L1 therapy, these findings support the use of prospective tumor sequencing to screen all patients with advanced prostate cancer for MSI-H/dMMR. Because not all patients with the MSI-H/dMMR phenotype respond, further studies should explore mechanisms of resistance.
Planets in young clusters are powerful probes of the evolution of planetary systems. Here we report the discovery of three planets transiting EPIC 247589423, a late-K dwarf in the Hyades ( 800 Myr) ...cluster, and robust detection limits for additional planets in the system. The planets were identified from their K2 light curves as part of our survey of young clusters and star-forming regions. The smallest planet has a radius comparable to Earth ( ), making it one of the few Earth-sized planets with a known, young age. The two larger planets are likely a mini-Neptune and a super-Earth, with radii of and , respectively. The predicted radial velocity signals from these planets are between 0.4 and 2 m s−1, achievable with modern precision RV spectrographs. Because the target star is bright (V = 11.2) and has relatively low-amplitude stellar variability for a young star (2-6 mmag), EPIC 247589423 hosts the best known planets in a young open cluster for precise radial velocity follow-up, enabling a robust test of earlier claims that young planets are less dense than their older counterparts.
The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region ...by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse--which today is reflected by shorter, older ancestry tracts--consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse--reflected by longer, younger tracts--is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub-continental source populations with far greater resolution than previously thought, even when limited pre-Columbian Caribbean haplotypes have survived.
In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 ...infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008-0.05; estimated odds ratios of 0.53-0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection.
ClinicalTrials.gov NCT00223080.
The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B and E) was previously shown to have a 31.2% efficacy rate. ...Plasma specimens from vaccine and placebo recipients were used in an extensive set of assays to identify correlates of HIV-1 infection risk. Of six primary variables that were studied, only one displayed a significant inverse correlation with risk of infection: the antibody (Ab) response to a fusion protein containing the V1 and V2 regions of gp120 (gp70-V1V2). This finding prompted a thorough examination of the results generated with the complete panel of 13 assays measuring various V2 Abs in the stored plasma used in the initial pilot studies and those used in the subsequent case-control study. The studies revealed that the ALVAC-HIV/AIDSVAX vaccine induced V2-specific Abs that cross-react with multiple HIV-1 subgroups and recognize both conformational and linear epitopes. The conformational epitope was present on gp70-V1V2, while the predominant linear V2 epitope mapped to residues 165-178, immediately N-terminal to the putative α4β7 binding motif in the mid-loop region of V2. Odds ratios (ORs) were calculated to compare the risk of infection with data from 12 V2 assays, and in 11 of these, the ORs were ≤1, reaching statistical significance for two of the variables: Ab responses to gp70-V1V2 and to overlapping V2 linear peptides. It remains to be determined whether anti-V2 Ab responses were directly responsible for the reduced infection rate in RV144 and whether anti-V2 Abs will prove to be important with other candidate HIV vaccines that show efficacy, however, the results support continued dissection of Ab responses to the V2 region which may illuminate mechanisms of protection from HIV-1 infection and may facilitate the development of an effective HIV-1 vaccine.
Background Debate exists within the surgical education community about whether 5 years is sufficient time to train a general surgeon, whether graduating chief residents are confident in their skills, ...why residents choose to do fellowships, and the scope of general surgery practice today. Study Design In May 2013, a 16-question online survey was sent to every general surgery program director in the United States for dissemination to each graduating chief resident (CR). Results Of the 297 surveys returned, 76% of CRs trained at university programs, 81% trained at 5-year programs, and 28% were going directly into general surgery practice. The 77% of CRs who had done >950 cases were significantly more comfortable than those who had done less (p < 0.0001). Only a few CRs were uncomfortable performing a laparoscopic colectomy (7%) or a colonoscopy (6%), and 80% were comfortable being on call at a Level I trauma center. Compared with other procedures, CRs were most uncomfortable with open common bile duct explorations (27%), pancreaticoduodenectomies (38%), hepatic lobectomies (48%), and esophagectomies (60%) (p < 0.00001). Of those going into fellowships, 67% said they truly had an interest in that specialty and only 7% said it was because they were not confident in their surgical skills. Conclusions Current graduates of general surgery residencies appear to be confident in their skills, including care of the trauma patient. Fellowships are being chosen primarily because of an interest in the subspecialty. General surgery residency no longer provides adequate training in esophageal or hepatopancreatobiliary surgery.
Whether mechanically unfolded fibronectin (Fn) is present within native extracellular matrix fibrils is controversial. Fn extensibility under the influence of cell traction forces has been proposed ...to originate either from the force-induced lengthening of an initially compact, folded quaternary structure as is found in solution (quaternary structure model, where the dimeric arms of Fn cross each other), or from the force-induced unfolding of type III modules (unfolding model). Clarification of this issue is central to our understanding of the structural arrangement of Fn within fibrils, the mechanism of fibrillogenesis, and whether cryptic sites, which are exposed by partial protein unfolding, can be exposed by cell-derived force. In order to differentiate between these two models, two fluorescence resonance energy transfer schemes to label plasma Fn were applied, with sensitivity to either compact-to-extended conformation (arm separation) without loss of secondary structure or compact-to-unfolded conformation. Fluorescence resonance energy transfer studies revealed that a significant fraction of fibrillar Fn within a three-dimensional human fibroblast matrix is partially unfolded. Complete relaxation of Fn fibrils led to a refolding of Fn. The compactly folded quaternary structure with crossed Fn arms, however, was never detected within extracellular matrix fibrils. We conclude that the resting state of Fn fibrils does not contain Fn molecules with crossed-over arms, and that the several-fold extensibility of Fn fibrils involves the unfolding of type III modules. This could imply that Fn might play a significant role in mechanotransduction processes.
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