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Carpal giant cell tumor of bone spanning multiple bones is a rare condition. We present a case of a man in his fifth decade with wrist pain who was found to have giant cell tumor of bone involving his capitate and hamate bones. This condition was successfully treated with intralesional curettage, argon beam coagulation, chemical cauterization and a cemented limited carpal fusion with satisfactory outcomes and no recurrence at 1-year postoperative follow-up.

PURPOSE: Unplanned excisions are defined as excisions of malignant tumors performed without preoperative cross-sectional imaging or diagnostic biopsy, frequently resulting in residual disease and re-excision secondary to positive surgical margins. The purpose of this study was to compare the relative morbidity of planned versus unplanned upper-extremity sarcoma excisions. METHODS: A single tertiary referral hospital pathology database was queried from January 2015 through 2022 for primary upper-extremity sarcomas (forearm, wrist, hand, and finger). Demographics, tumor features, survival characteristics, and outcomes were retrospectively reviewed. RESULTS: Forty-two upper-extremity sarcoma patients were identified, two-thirds of whom had unplanned excisions. Those with unplanned excisions were more likely to be female (relative risk [RR]: 1.9; P = .002), undergo initial excision at a nonsarcoma center (RR: 14.0; P < .001), have masses distal to the forearm (RR: 1.6; P = .02), and have smaller masses (4.8 vs 7.4 cm, P = .03). 71.4% of tumors were high grade, and 60.7% less than 5 cm in size.Unplanned excisions had positive margins in 96.4% of cases and were more likely to undergo re-excision (odds ratio [OR]: 20.0; P = .001), more total resections (2.7 vs 1.4, P = .009), sacrifice of neurovascular structures (OR: 6.1; P = .04), adjuvant radiation therapy (OR: 4.5; P = .05), adjuvant systemic therapy (OR: 10.9; P = .03), or experience a complication (OR: 17.6; P = .002) at an average of 38.0 months of follow-up.Nearly half of all unplanned excision patients developed a local recurrence or metastatic disease. Six patients required an amputation versus one in the planned cohort (P = .17), and 26.5% of patients died at an average of 32.5 months from presentation. CONCLUSIONS: Distal upper-extremity sarcoma excisions are frequently unplanned, with high rates of morbidity compared with planned excisions. Surgeons should have a low threshold for cross-sectional imaging and core needle biopsy of atypical lesions, irrespective of size, with referral to a sarcoma center. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

ObjectiveWe aimed to evaluate the difference in 30-day outcomes after surgical management of proximal humerus fractures (PHFs) between patients with and without chronic liver disease as defined by a MELD score greater than 10.DesignThis was a retrospective database review.SettingAll centers participating in the American College of Surgeons National Surgical Quality Improvement Program database were included.Patients/participantsPatients with proximal humerus fractures who (1) underwent ORIF, HA, or SA and (2) had calculable MELD scores were included.InterventionOpen reduction and internal fixation, hemiarthroplasty, or shoulder arthroplasty was used for treatment.Main outcome measurementsThirty-day complications, mortality, readmission, and reoperation rates were measured.ResultsOf the total 1732 PHF patients identified, 300 had a MELD score higher than 10. After propensity matching by significant covariates, MELD score higher than 10 was found to be significantly associated with higher rates of 30-day mortality, 30-day readmission, transfusion within 72 hours, and systemic complications. Among patients with a MELD score higher than 10, treatment with SA or HA instead of ORIF was associated with a higher rate of transfusion and longer operative time. There were no significant differences between treatment cohorts regarding mortality, reoperation, readmission, or complications.ConclusionsA MELD score higher than 10 is associated with higher risk of surgical complications, transfusion, and death in patients undergoing surgery for proximal humerus fractures. Among patients with a MELD score higher than 10, ORIF was associated with a lower transfusion rate and shorter operative time than arthroplasty or hemiarthroplasty.Level of evidencePrognostic Level III.

BACKGROUND: End-stage renal disease (ESRD) and renal transplant (RT) patients are known to have more perioperative and postoperative complications after arthroplasty surgeries when compared to patients without. We hypothesize that RT patients undergoing shoulder arthroplasty (SA) have fewer systemic and surgical complications when compared to ESRD patients undergoing SA. METHODS: This was a retrospective review from the PearlDiver Patient Record Database. International Classification of Diseases and Current Procedural Terminology codes were used to identify patients who had undergone primary total and reverse shoulder arthroplasty, respectively, and subsequent surgical revisions. Unadjusted univariate analysis of patient demographics, Charlson Cormorbidty Index, and surgical complications at 90 days, 1 year, and 2 years after was performed using chi-squared testing. Multivariate logistic regression analyses were subsequently performed for systemic complications and prosthesis outcomes at all time points. RESULTS: Of 1191 patients with ESRD or previous RT and who underwent either total shoulder arthroplasty or reverse total shoulder arthroplasty, 1042 (87.5%) had ESRD and 149 (12.5%) had a previous RT. ESRD SA patients were more likely to have hypertension, liver disease, coronary artery disease, and hypothyroidism. Interestingly no statistical significance was found in multivariate analysis for systemic complications at 90 days, nor for surgical complications at the 90-day, 1-year, or 2-year mark between ESRD and RT cohorts. CONCLUSION: SAs have comparable outcomes in ESRD and RT patients. The differing conclusions among studies might be partially accounted for by the demographic differences and comorbidities between these 2 patient populations. Providers should continue to provide appropriate counseling concerning risks, benefits, and timing of SA for these patients.

Background: Indications for reverse total shoulder arthroplasty (RTSA) have been expanding. In addition to degenerative joint disease (DJD), RTSA is now being used to treat proximal humerus fractures (PHF). The purpose of this study was to compare postoperative complications in RTSA performed for DJD versus PHF. Methods: A retrospective analysis of the PearlDiver National Database was performed. International Classification of Diseases 10 codes were used to identify RTSA patients from 2015-2018 and separate them into DJD and PHF cohorts. Demographics, comorbidities, and hospital data were identified and compared using a two-sample t-test and chi-squared test. Systemic complications at 90 days and surgical complications at 90 days, 1 year, and 2 years were compared using multivariable logistic regression. Results: Fifteen thousand six hundred seventy eight patients (92.6% DJD, 7.4% PHF) were identified. PHF patients were more likely to be older (70.3 vs. 69.7 years, P = .026), female (83.5% vs. 62.2%, P < .001), and have more medical comorbidities (Charlson Comorbidity Index 3.42 vs. 3.17, P = .006) than DJD patients. After controlling for patient factors, PHF patients were more likely than DJD patients to develop urinary tract infection (odds ratio [OR] 1.65, P < .001), deep vein thrombosis (OR 1.76, P = .024), and hematoma (OR 3.83, P < .001) within 90 days of RTSA. At 90 days, 1 year, and 2 years postoperatively, RTSA for PHF patients were also more likely than RTSA for DJD patients to sustain a periprosthetic fracture (OR 2.57, P < .001) and instability (OR 2.02, P < .001). Conclusions: Patients with DJD and PHF undergoing RTSA represent different patient populations with distinct postoperative clinical outcomes. RTSA for PHF has inferior outcomes, which is significant in an era of bundled payments.

Abstract On both normative and pragmatic grounds, I make a case for “decent jobs” over the current discourse around “good jobs.” I define decent jobs as ones that reflect sustained worker influence over the terms and conditions of work. Making decent jobs necessarily entails groups of workers capable of engaging strategically with firms and governments. Where will these groups come from? Changes in technology, the structure of production, and boundaries of the firm all point to profound difficulties in sustaining collective action centered on workplace relationships and identities. Networks of workers organized around mutual aid show some promise, but connecting these groups to concerted action on the shop floor implies numerous organizational and governance challenges.

IntroductionThe most common surgical options for geriatric proximal humerus fractures are open reduction and internal fixation (ORIF), hemiarthroplasty (HA), and reverse total shoulder arthroplasty. We used a longitudinal inpatient discharge database to determine the cumulative incidence of conversion to arthroplasty after ORIF of geriatric proximal humerus fractures. The rates of short-term complications and all-cause reoperation were also compared.Patients and methodsAll patients 65 or older who sustained a proximal humerus fracture and underwent either ORIF, HA, or shoulder arthroplasty (SA) as an inpatient from 2000 through 2017 were identified. Survival analysis was performed with ORIF conversion to arthroplasty and all-cause reoperation as the endpoints of interest. Rates of 30-day readmission and short-term complications were compared. Trends in procedure choice and outcomes over the study period were analyzed.ResultsA total of 27 102 geriatric patients that underwent inpatient surgical management of proximal humerus fractures were identified. Among geriatric patients undergoing ORIF, the cumulative incidence of conversion to arthroplasty within 10 years was 8.2%. The 10-year cumulative incidence of all-cause reoperation was 12.1% for ORIF patients and less than 4% for both HA and SA patients. Female sex was associated with increased risk of ORIF conversion and younger age was associated with higher all-cause reoperation. ORIF was associated with higher 30-day readmission and short-term complication rates. Over the study period, the proportion of patients treated with ORIF or SA increased while the proportion of patients treated with HA decreased. Short-term complication rates were similar between arthroplasty and ORIF patients in the later cohort (2015-2017).ConclusionThe 10-year cumulative incidence of conversion to arthroplasty for geriatric patients undergoing proximal humerus ORIF as an inpatient was found to be 8.2%. All-cause reoperations, short-term complications, and 30-day readmissions were all significantly lower among patients undergoing arthroplasty, but the difference in complication rate between arthroplasty and ORIF was attenuated in more recent years. Younger age was a risk factor for reoperation and female sex was associated with increased risk of requiring conversion to arthroplasty after ORIF.

There is an urgent need to develop new therapies for colorectal cancer that has metastasized to the liver and, more fundamentally, to develop improved preclinical platforms of colorectal cancer liver metastases (CRCLM) to screen therapies for efficacy. To this end, we developed a multi-well perfusable bioreactor capable of monitoring CRCLM patient-derived organoid response to a chemotherapeutic gradient. CRCLM patient-derived organoids were cultured in the multi-well bioreactor for 7 days and the subsequently established gradient in 5-fluorouracil (5-FU) concentration resulted in a lower IC50 in the region near the perfusion channel versus the region far from the channel. We compared behaviour of organoids in this platform to two commonly used PDO culture models: organoids in media and organoids in a static (no perfusion) hydrogel. The bioreactor IC50 values were significantly higher than IC50 values for organoids cultured in media whereas only the IC50 for organoids far from the channel were significantly different than organoids cultured in the static hydrogel condition. Using finite element simulations, we showed that the total dose delivered, calculated using area under the curve (AUC) was similar between platforms, however normalized viability was lower for the organoid in media condition than in the static gel and bioreactor. Our results highlight the utility of our multi-well bioreactor for studying organoid response to chemical gradients and demonstrate that comparing drug response across these different platforms is nontrivial.

In this article we examine the relation between variation theory and Maria Montessori’s didactic theory. Montessori believed that training and sharpening of the child’s senses are crucial for their continued learning; she therefore developed specific sensorial materials to be used in Montessori preschools for such a purpose. As noted by interpreters of Montessori education, a key principle in this material, as well as in variation theory, is the use of variation and invariance. However, in this article, lessons in two different areas than the training of the senses are analysed from a variation-theoretical perspective on learning; these lessons originate from Montessori’s own writings and from extracts from Montessori training courses. The result shows that a systematic use of variation and invariance can be seen as a more fundamental part of Montessori’s didactic theory and is not only applied in the sensorial training. The article will offer theoretical concepts useful when explaining why lessons in various areas should be presented in the way they are described.

On 6 May 2022, 70 years after Maria Montessori’s death, Stockholm University and the Department of Education and Didactics organized an international Montessori symposium. The idea was to present a breadth of research on Maria Montessori. The symposium dealt with Maria Montessori in the interwar period, an analysis of the history of ideas. Another presentation suggested possible research models to study this large field. The symposium also presented interpretations of Montessori’s writings that point her out as a visionary and pioneer in education for a sustainable world. An additional research area addressed was the potential of neuroscience to examine the effects of teaching theory and learning in Montessori education. Finally, this report describes a study on whether Montessori-inspired education compared to traditional education stands up in areas of socio-economic disadvantage.

BACKGROUND: Renal osteodystrophy predisposes renal disease patients to fracture. Proximal humerus fractures (PHFs) frequently undergo open reduction internal fixation (ORIF); however, the effect of renal disease on outcomes is unknown. METHODS: A retrospective review of the Nationwide Readmissions Database used International Classification of Diseases, 9th Revision, codes to identify patients who underwent ORIF for closed PHF from 2010 to 2014 with no renal disease, predialysis chronic renal disease (CRD), and end-stage renal disease (ESRD). RESULTS: A total of 85,433 patients were identified, including 5498 (6.4%) CRD and 636 (0.7%) ESRD. CRD and ESRD patients had increased age, comorbidities, and rates of Medicare insurance. After adjusting for differences, CRD and ESRD patients were at increased risk of any complication (odds ratio [OR] 2.48, 1.66), blood transfusion (OR 1.85, 3.31), respiratory complications (OR 1.14, 1.59), acute renal failure (OR 4.80, 1.67), systemic infection (OR 2.00, 3.14), surgical site infection (OR 1.52, 3.87), longer length of stay (7.1 and 12.9 days vs. 5.9 days), and higher cost ($21,669 and $35,413 vs. $20,394) during index hospitalization, as well as surgical site infection (OR 1.43, 3.03) and readmission (OR 1.61, 3.69) within 90 days of discharge, respectively, compared with no renal disease patients. During index hospitalization, CRD patients also had increased risk for periprosthetic fracture (OR 4.97) and cardiac complications (OR 1.47), whereas ESRD patients had increased risk of mortality (OR 5.79), wound complication (2.67), and deep vein thrombosis (OR 16.70). CONCLUSION: These findings suggest renal patients are at increased risk for complications after PHF ORIF, highlighting the importance of close perioperative monitoring and appropriate patient selection in this population, including strong consideration of nonoperative management.

This article reports on a study in which, for five weeks, the English lessons of two classes of 11--12 year olds in Sweden were based on Roald Dahl's "Fantastic Mr Fox." To promote the learners' engagement with the text, support understanding, and facilitate incidental vocabulary acquisition, a range of language-focused tasks were designed within the framework of the Storyline approach. In Storyline, a fictive world is created in the classroom. The story develops when learners, working in the same small groups, collaborate on open so-called key questions, which structure the Storyline, introduce happenings and problems, and link with the syllabus. Another characteristic is the integration of practical and theoretical subject content. Learners' art work and texts are displayed on a frieze, or walls of the classroom, creating a visual record of the developing story. The study also investigated the influence on learning of the book's illustrations, and the learners' own drawings. The majority of the learners made gains in vocabulary, as evidenced in pre- and post-tests, writing and speaking tasks. While some learners had never thought about illustrations and drawings as a support, for many, both of these were found to be helpful.

The theory of Montessori education has been interpreted by some researchers to be vaguely formulated. However, as shown in previous research, Maria Montessori's didactic approach to teaching and learning mathematics is fully consistent with variation theory and the theory of embodiment. Dr. Montessori used the theoretical concept of "isolation of quality," which means that the learning objects have to be kept identical except for one variable, which has to differ to be perceptible. This concept is in alignment with variation theory, which emphasizes variation as a necessary condition for learners to discern aspects of an object of learning. The other theory applied in this article is the theory of embodiment: important cognitive functions are fundamentally grounded in action that is concordant with Dr. Montessori's view that mind and movement are parts of the same entity. This article reports on a qualitative single-case study with a formative intention in which we investigated the significance of being acquainted with variation theory and the theory of embodiment when working with Montessori material. The study analyzes a teacher's mathematics presentations with the Montessori material and the children's work with this material, using Epistemological Move Analysis, which focuses on how the teacher directs children's learning. The analysis was shared with the teacher to support her awareness of the ways teaching can be developed from a variation and embodiment theoretical perspective. Results show that the teacher's awareness of why a specific learning object must be treated in accordance with variation theory and embodiment seems to promote a more constructive and effective way to direct children's learning.

ABSTRACT Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female FVB/N mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.IMPORTANCEHuman papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.

BackgroundAs primary total knee arthroplasty volume continues to increase, so will the number of revision total knee arthroplasty (rTKA) procedures. The purpose of this study is to provide an updated perspective on the incidence, indications, and financial burden of rTKA in the United States.Material and methodsThis was a retrospective epidemiologic analysis using the National Inpatient Sample. International Classification of Diseases ninth and tenth revision codes were used to identify patients who underwent rTKA and create cohorts based on rTKA indications from 2012 to 2019. National and regional trends for length of stay, cost, and discharge location were evaluated.ResultsA total of 505,160 rTKA procedures were identified. The annual number of rTKA procedures increased by 29.6% over the study period (56,490 to 73,205). The top 3 indications for rTKA were aseptic loosening (23.1%), periprosthetic joint infection (PJI) (20.4%), and instability (11.0%). Over the study period, the proportion of patients discharged to skilled nursing facility decreased from 31.7% to 24.1% (P < .001). Hospital length of stay decreased from 4.0 days in 2012 to 3.8 days in 2019 (P < .001). Hospital costs increased by $1300 from $25,730 to $27,077 (P < .001). The proportion of rTKA cases performed at urban academic centers increased (52.1% to 74.3%, P < .001) while that at urban nonacademic centers decreased (39.0% to 19.2%, P < .001).ConclusionThe top 3 indications for rTKA were aseptic loosening, PJI, and instability, with PJI becoming the most common indication in 2019. These cases are increasingly being performed at urban academic centers and away from urban nonacademic centers.Level of evidence3 (Retrospective cohort study).

The COVID-19 pandemic and ensuing social distancing requirements resulted in an abrupt transition in the provision of most mental healthcare to telehealth; yet it was, at first, unclear whether patients' emotional expressions - of great import to the success of many psychodynamic therapies - could be facilitated using teletherapy. This article first presents a targeted literature review focused on emotional expressions in psychotherapy and implementing psychodynamic therapy over telehealth and then describes our clinical experience transitioning a psychodynamically-informed, evidence-based, and experiential group treatment for chronic pain, emotional awareness and expression therapy (EAET), to video telehealth at VA Greater Los Angeles Healthcare System. We discuss barriers we encountered in our implementation of EAET over video telehealth but also illustrate the ultimate success of the approach using verbatim excerpts from our therapeutic work, which aim to demonstrate the potential to facilitate powerful emotional expressions over video telehealth when conducting a psychodynamically-informed treatment. We examine the possible applications for video telehealth to maintain emotionally focused, psychodynamic psychotherapy administration and enhance its teaching and training. Although we describe limitations of our specific approach, ultimately, our experience supports the potential efficacy of experiential, emotion-focused psychodynamic therapies in a telehealth setting.

Background: End-stage renal disease (ESRD) and renal transplant (RT) patients are known to have more perioperative and postoperative complications after arthroplasty surgeries when compared to patients without. We hypothesize that RT patients undergoing shoulder arthroplasty (SA) have fewer systemic and surgical complications when compared to ESRD patients undergoing SA. Methods: This was a retrospective review from the PearlDiver Patient Record Database. International Classification of Diseases and Current Procedural Terminology codes were used to identify patients who had undergone primary total and reverse shoulder arthroplasty, respectively, and subsequent surgical revisions. Unadjusted univariate analysis of patient demographics, Charlson Cormorbidty Index, and surgical complications at 90 days, 1 year, and 2 years after was performed using chi-squared testing. Multivariate logistic regression analyses were subsequently performed for systemic complications and prosthesis outcomes at all time points. Results: Of 1191 patients with ESRD or previous RT and who underwent either total shoulder arthroplasty or reverse total shoulder arthroplasty, 1042 (87.5%) had ESRD and 149 (12.5%) had a previous RT. ESRD SA patients were more likely to have hypertension, liver disease, coronary artery disease, and hypothyroidism. Interestingly no statistical significance was found in multivariate analysis for systemic complications at 90 days, nor for surgical complications at the 90-day, 1-year, or 2-year mark between ESRD and RT cohorts. Conclusion: SAs have comparable outcomes in ESRD and RT patients. The differing conclusions among studies might be partially accounted for by the demographic differences and comorbidities between these 2 patient populations. Providers should continue to provide appropriate counseling concerning risks, benefits, and timing of SA for these patients.

Abstract The increasing concentration of CO2 in the atmosphere and its impact on the climate are matters of significant concern. Extensive research is being conducted on molecular catalysts to electrochemically reduce CO2 into valuable products to disrupt the unidirectional carbon flow. This study compares two manganese bipyridine catalysts, tailored with four or two benzylic diethylamine groups in the secondary coordination sphere. Either of these amine‐bearing scaffolds positioned close to the Mn center serves as effective proton relays to facilitate the formation of the corresponding Mn hydride intermediate. Alongside competitive H2 evolution, the reaction of this crucial intermediate with CO2 leads to formate. Our findings underscore the pronounced influence of external Brønsted acids on product selectivity. Notably, when employing the catalyst bearing four amine groups, the HCOO−/H2 ratio varies from 81 : 3 with 1.0 M iPrOH to 16 : 64 with 1.0 M PhOH, while the Mn complex adorned with two amine pendant groups consistently favors HCOO−, irrespective of the utilized proton sources. Infrared spectroelectrochemistry and density‐functional theory calculations unveil distinct disparities in the reactivity of the Mn hydrides toward CO2 due to the change of ligand bulkiness in the two cases. This work substantiates the importance of modulating spatial accessibility while modifying the second sphere encompassing molecular catalysts.

The aim of this article is to understand how Montessori education, according to Maria Montessori, will enable 6--12-year-olds to meet future challenges and to care for and contribute to the wellbeing of society and the planet as a whole. This article reports on a qualitative content analysis of four books written by Maria Montessori. The analysis shows how the structure in Montessori´s curriculum for these ages lays the foundation to cultivate an understanding of the interdependence of living and non-living elements in the ecosystem and the collective responsibility for human coexistence. Further, the analysis shows how children are provided with an emotional tie to the universal approach she advocates and opportunities to develop a sense of empowerment. The topicality of Montessori education is discussed in relation to different teaching traditions. We argue that Montessori education constitutes a concrete example of a teaching tradition whose democratic mission is evident.

Abstract. Objective:. We aimed to evaluate the difference in 30-day outcomes after surgical management of proximal humerus fractures (PHFs) between patients with and without chronic liver disease as defined by a MELD score greater than 10. Design:. This was a retrospective database review. Setting:. All centers participating in the American College of Surgeons National Surgical Quality Improvement Program database were included. Patients/Participants:. Patients with proximal humerus fractures who (1) underwent ORIF, HA, or SA and (2) had calculable MELD scores were included. Intervention:. Open reduction and internal fixation, hemiarthroplasty, or shoulder arthroplasty was used for treatment. Main outcome measurements:. Thirty-day complications, mortality, readmission, and reoperation rates were measured. Results:. Of the total 1732 PHF patients identified, 300 had a MELD score higher than 10. After propensity matching by significant covariates, MELD score higher than 10 was found to be significantly associated with higher rates of 30-day mortality, 30-day readmission, transfusion within 72 hours, and systemic complications. Among patients with a MELD score higher than 10, treatment with SA or HA instead of ORIF was associated with a higher rate of transfusion and longer operative time. There were no significant differences between treatment cohorts regarding mortality, reoperation, readmission, or complications. Conclusions:. A MELD score higher than 10 is associated with higher risk of surgical complications, transfusion, and death in patients undergoing surgery for proximal humerus fractures. Among patients with a MELD score higher than 10, ORIF was associated with a lower transfusion rate and shorter operative time than arthroplasty or hemiarthroplasty. Level of Evidence:. Prognostic Level III.

Abstract Alcohols are one of the most common organic compound classes among natural and synthetic products. Thus, methods for direct removal of C−OH groups without the need for wasteful pre‐functionalization are of great synthetic interest to unlock the full synthetic potential of the compound class. Herein, electroreductive C−OH bond activation and subsequent deoxygenative C−H and C−C bond formation of benzylic and propargylic alcohols are demonstrated along with mechanistic insights. Experimental and theoretical studies indicate that the reductive C−OH bond cleavage furnishes an open shell intermediate that undergoes a radical‐polar crossover to the corresponding carbanion that subsequently undergoes protonation to furnish alkane products. Furthermore, we demonstrate that the carbanion can be trapped with CO2 to form arylacetic acids. The cathodic transformations are efficiently balanced by the anodic oxidation of sub‐stoichiometric borohydride additives, a strategy that serves as a highly attractive alternative to the use of sacrificial metal anodes.

ABSTRACT HIV-1 virion production is inefficient in cells derived from mice and other rodents reflecting cell-intrinsic defects to interactions between the HIV-1 auxiliary proteins Tat and Rev and host dependency factors CCNT1 (Cyclin T1) and XPO1 (exportin-1, also known as CRM1), respectively. In human cells, Tat binds CCNT1 to enhance viral RNA transcription and Rev recruits XPO1 to mediate the nuclear export of intron-containing viral RNA. In mouse cells, Tat’s interactions with CCNT1 are inefficient, mapped to a single species-specific residue Y261 instead of C261 in humans. Rev interacts poorly with murine XPO1, mapped to a trio of amino acids T411/V412/S414 instead of P411/M412/F414 in humans. To determine if these discrete species-specific regions of otherwise conserved housekeeping proteins represent viable targets for inhibiting HIV-1 replication in humans, herein, we employed CRISPR/Cas9 to recode the relevant regions of CCNT1 and XPO1 in human CD4+ T cells. While efforts to modify XPO1 were inconclusive, we generated isogenic CCNT1.C261Y cell lines exhibiting remarkable resistance to HIV-1 Tat, exhibiting near total inactivation of viral gene expression for all X4- and R5-tropic HIV-1 strains tested, as well as the more distantly related primate lentiviruses HIV-2 and SIVagm. Induction of viral reactivation using latency reversal agents (LRAs) was also restricted in CCNT1.C261Y cells. These studies validate a minor and naturally occurring, species-specific difference in a conserved human host factor as a compelling potential target for achieving broad-acting cell-intrinsic resistance to HIV’s post-integration phases. Importance Unlike humans, mice are unable to support HIV-1 infection. This is due, in part, to a constellation of defined minor, species-specific differences in conserved host proteins needed for viral gene expression. Here, we used precision CRISPR/Cas9 gene editing to engineer a “mousified” version of one such host protein, cyclin T1 (CCNT1), in human T cells. CCNT1 is essential for efficient HIV-1 transcription, making it an intriguing target for gene-based inactivation of virus replication. We show that isogenic cell lines engineered to encode CCNT1 bearing a single mouse-informed amino acid change (tyrosine in place of cysteine at position 261) exhibit potent, durable, and broad-spectrum resistance to HIV-1 and other pathogenic lentiviruses, and with no discernible impact on host cell biology. These results provide proof of concept for targeting CCNT1 in the context of one or more functional HIV-1 cure strategies.

BackgroundAnterior lumbar interbody fusion (ALIF) is commonly utilized in lumbar degenerative pathologies. Standalone ALIF (ST-ALIF) systems were developed to avoid added morbidity, surgical time, and cost of anterior and posterior fusion (APF). Controversy exists in the literature about which of these two techniques yields superior clinical and radiographic outcomes, and few studies have directly compared them. This study seeks to compare ST-ALIF and APF in terms of sagittal correction and surgical complications.MethodsNinty-two consecutive ALIF cases performed from 2013-2018 were retrospectively reviewed and separated into 2 groups. Radiographic measurements were performed on pre- and post-operative radiographs, including segmental lordosis (SL), lumbar lordosis (LL), and pelvic incidence-lumbar lordosis mismatch (PI-LL). Surgical complications were determined. Statistical analysis was performed using chi-square test of homogeneity, Fisher's exact test, and independent sample t-test. Comparisons between groups were deemed statistically significant at the P

OBJECTIVE:Current guidelines recommend initiation of venous thromboembolism (VTE) chemoprophylaxis within 72 hours of spinal cord injury (SCI). This study investigated the safety and efficacy of chemoprophylaxis within 24 hours of surgery for SCI. METHODS:A retrospective review of 97 consecutive patients who underwent surgery for acute traumatic SCI at a single level 1 trauma center from 2013-2018 was performed. VTE/postoperative bleeding rates during hospitalization, demographics, medical/surgical complications, drain output, length of stay, and disposition were obtained. Chi-square with odds ratios (ORs), 1-way analysis of variance, and logistic regression were performed to establish significant differences between groups. RESULTS:Seventy-nine patients were included, 49 received chemoprophylaxis within 24 hours and 20 within 24-72 hours. Cohort characteristics included an average age of 51.8 years, 77.2% male, 62.0% cervical, and 35.4% thoracic SCIs. Using the American Spinal Injury Association Impairment Scale (AIS), 39.2% were AIS-A injuries, 19.0% AIS-B, 25.3% AIS-C, and 16.5% AIS-D. Unfractionated heparin was administered in 88.6% of patients and 11.4% received low molecular weight heparin. Chemoprophylaxis within 24 hours of surgery was associated with a lower rate of VTE (6.1% vs. 35.0%; OR, 0.121; 95% confidence interval [CI], 0.027-0.535) and deep vein thrombosis (4.1% vs. 30.0%; OR, 0.099; 95% CI, 0.018-0.548) versus 24-72 hours. Pulmonary embolism rates were not significantly different (6.1% vs. 5.0%, p = 1.0). There were no postoperative bleeding complications and no significant difference in drain output between cohorts. CONCLUSION:Early VTE chemoprophylaxis is effective with lower VTE rates when initiated within 24 hours of surgery for SCI and is safe with no observed postoperative bleeding complications.

Novel dual-ionic imidazolium salts are shown to display excellent catalytic activity for cycloaddition of carbon dioxide and epoxides under room temperature and atmospheric pressure (0.1 MPa) without any solvent and co-catalyst leading to 96.1% product yield. It can be reused five times to keep the product yield over 90%. These intriguing results are attributed to a new reaction mechanism, which is supported by theoretical calculations along with the measurements of 13C NMR spectrum and Fourier transform infrared spectroscopy (FT-IR). The excellent catalytic activity can be traced to a CO2-philic group along with an electrophilic hydrogen atom. Our work shows that incorporation of CO2-philic group is an feasible pathway to develop the new efficient ionic liquids.

Introduction The most common surgical options for geriatric proximal humerus fractures are open reduction and internal fixation (ORIF), hemiarthroplasty (HA), and reverse total shoulder arthroplasty. We used a longitudinal inpatient discharge database to determine the cumulative incidence of conversion to arthroplasty after ORIF of geriatric proximal humerus fractures. The rates of short-term complications and all-cause reoperation were also compared. Patients and Methods All patients 65 or older who sustained a proximal humerus fracture and underwent either ORIF, HA, or shoulder arthroplasty (SA) as an inpatient from 2000 through 2017 were identified. Survival analysis was performed with ORIF conversion to arthroplasty and all-cause reoperation as the endpoints of interest. Rates of 30-day readmission and short-term complications were compared. Trends in procedure choice and outcomes over the study period were analyzed. Results A total of 27 102 geriatric patients that underwent inpatient surgical management of proximal humerus fractures were identified. Among geriatric patients undergoing ORIF, the cumulative incidence of conversion to arthroplasty within 10 years was 8.2%. The 10-year cumulative incidence of all-cause reoperation was 12.1% for ORIF patients and less than 4% for both HA and SA patients. Female sex was associated with increased risk of ORIF conversion and younger age was associated with higher all-cause reoperation. ORIF was associated with higher 30-day readmission and short-term complication rates. Over the study period, the proportion of patients treated with ORIF or SA increased while the proportion of patients treated with HA decreased. Short-term complication rates were similar between arthroplasty and ORIF patients in the later cohort (2015-2017). Conclusion The 10-year cumulative incidence of conversion to arthroplasty for geriatric patients undergoing proximal humerus ORIF as an inpatient was found to be 8.2%. All-cause reoperations, short-term complications, and 30-day readmissions were all significantly lower among patients undergoing arthroplasty, but the difference in complication rate between arthroplasty and ORIF was attenuated in more recent years. Younger age was a risk factor for reoperation and female sex was associated with increased risk of requiring conversion to arthroplasty after ORIF.

HIV-1 spreads efficiently through direct cell-to-cell transmission at virological synapses (VSs) formed by interactions between HIV-1 envelope proteins (Env) on the surface of infected cells and CD4 receptors on uninfected target cells. Env-CD4 interactions bring the infected and uninfected cellular membranes into close proximity and induce transport of viral and cellular factors to the VS for efficient virion assembly and HIV-1 transmission. Using novel, cell-specific stable isotope labeling and quantitative mass spectrometric proteomics, we identified extensive changes in the levels and phosphorylation states of proteins in HIV-1 infected producer cells upon mixing with CD4+ target cells under conditions inducing VS formation. These coculture-induced alterations involved multiple cellular pathways including transcription, TCR signaling and, unexpectedly, cell cycle regulation, and were dominated by Env-dependent responses. We confirmed the proteomic results using inhibitors targeting regulatory kinases and phosphatases in selected pathways identified by our proteomic analysis. Strikingly, inhibiting the key mitotic regulator Aurora kinase B (AURKB) in HIV-1 infected cells significantly increased HIV activity in cell-to-cell fusion and transmission but had little effect on cell-free infection. Consistent with this, we found that AURKB regulates the fusogenic activity of HIV-1 Env. In the Jurkat T cell line and primary T cells, HIV-1 Env:CD4 interaction also dramatically induced cell cycle-independent AURKB relocalization to the centromere, and this signaling required the long (150 aa) cytoplasmic C-terminal domain (CTD) of Env. These results imply that cytoplasmic/plasma membrane AURKB restricts HIV-1 envelope fusion, and that this restriction is overcome by Env CTD-induced AURKB relocalization. Taken together, our data reveal a new signaling pathway regulating HIV-1 cell-to-cell transmission and potential new avenues for therapeutic intervention through targeting the Env CTD and AURKB activity.

Background: Renal osteodystrophy predisposes renal disease patients to fracture. Proximal humerus fractures (PHFs) frequently undergo open reduction internal fixation (ORIF); however, the effect of renal disease on outcomes is unknown. Methods: A retrospective review of the Nationwide Readmissions Database used International Classification of Diseases, 9th Revision, codes to identify patients who underwent ORIF for closed PHF from 2010 to 2014 with no renal disease, predialysis chronic renal disease (CRD), and end-stage renal disease (ESRD). Results: A total of 85,433 patients were identified, including 5498 (6.4%) CRD and 636 (0.7%) ESRD. CRD and ESRD patients had increased age, comorbidities, and rates of Medicare insurance. After adjusting for differences, CRD and ESRD patients were at increased risk of any complication (odds ratio [OR] 2.48, 1.66), blood transfusion (OR 1.85, 3.31), respiratory complications (OR 1.14, 1.59), acute renal failure (OR 4.80, 1.67), systemic infection (OR 2.00, 3.14), surgical site infection (OR 1.52, 3.87), longer length of stay (7.1 and 12.9 days vs. 5.9 days), and higher cost ($21,669 and $35,413 vs. $20,394) during index hospitalization, as well as surgical site infection (OR 1.43, 3.03) and readmission (OR 1.61, 3.69) within 90 days of discharge, respectively, compared with no renal disease patients. During index hospitalization, CRD patients also had increased risk for periprosthetic fracture (OR 4.97) and cardiac complications (OR 1.47), whereas ESRD patients had increased risk of mortality (OR 5.79), wound complication (2.67), and deep vein thrombosis (OR 16.70). Conclusion: These findings suggest renal patients are at increased risk for complications after PHF ORIF, highlighting the importance of close perioperative monitoring and appropriate patient selection in this population, including strong consideration of nonoperative management.

There is an urgent need to develop new therapies for colorectal cancer that has metastasized to the liver and, more fundamentally, to develop improved preclinical platforms of colorectal cancer liver metastases (CRCLM) to screen therapies for efficacy. To this end, we developed a multi-well perfusable bioreactor capable of monitoring CRCLM patient-derived organoid response to a chemotherapeutic gradient. CRCLM patient-derived organoids were cultured in the multi-well bioreactor for 7 days and the subsequently established gradient in 5-fluorouracil (5-FU) concentration resulted in a lower IC50 in the region near the perfusion channel versus the region far from the channel. We compared behaviour of organoids in this platform to two commonly used PDO culture models: organoids in media and organoids in a static (no perfusion) hydrogel. The bioreactor IC50 values were significantly higher than IC50 values for organoids cultured in media whereas only the IC50 for organoids far from the channel were significantly different than organoids cultured in the static hydrogel condition. Using finite element simulations, we showed that the total dose delivered, calculated using area under the curve (AUC) was similar between platforms, however normalized viability was lower for the organoid in media condition than in the static gel and bioreactor. Our results highlight the utility of our multi-well bioreactor for studying organoid response to chemical gradients and demonstrate that comparing drug response across these different platforms is nontrivial.

Machine learning tools have proven useful across biological disciplines, allowing researchers to draw conclusions from large datasets, and opening up new opportunities for interpreting complex and heterogeneous biological data. Alongside the rapid growth of machine learning, there have also been growing pains: some models that appear to perform well have later been revealed to rely on features of the data that are artifactual or biased; this feeds into the general criticism that machine learning models are designed to optimize model performance over the creation of new biological insights. A natural question arises: how do we develop machine learning models that are inherently interpretable or explainable? In this manuscript, we describe the SWIF(r) reliability score (SRS), a method building on the SWIF(r) generative framework that reflects the trustworthiness of the classification of a specific instance. The concept of the reliability score has the potential to generalize to other machine learning methods. We demonstrate the utility of the SRS when faced with common challenges in machine learning including: 1) an unknown class present in testing data that was not present in training data, 2) systemic mismatch between training and testing data, and 3) instances of testing data that have missing values for some attributes. We explore these applications of the SRS using a range of biological datasets, from agricultural data on seed morphology, to 22 quantitative traits in the UK Biobank, and population genetic simulations and 1000 Genomes Project data. With each of these examples, we demonstrate how the SRS can allow researchers to interrogate their data and training approach thoroughly, and to pair their domain-specific knowledge with powerful machine-learning frameworks. We also compare the SRS to related tools for outlier and novelty detection, and find that it has comparable performance, with the advantage of being able to operate when some data are missing. The SRS, and the broader discussion of interpretable scientific machine learning, will aid researchers in the biological machine learning space as they seek to harness the power of machine learning without sacrificing rigor and biological insight.

This study focused on understanding how college student educators use The Student Affairs Professional Facebook group. Through descriptive and qualitative analysis of posts, shares, comments, and interactions, this study identifies central topics and issues discussed over a 14-month period. This research shows how college student educators use this Facebook group to share professional development, offer learning/training resources, disseminate graduate education information, to offer/solicit advice, engage in dialogue regarding equity/social justice/inclusion, support colleagues, and share humor/stories.

Summary: Neurons make converging and diverging synaptic connections with distinct partner types. Whether synapses involving separate partners demonstrate similar or distinct structural motifs is not yet well understood. We thus used serial electron microscopy in mouse retina to map output synapses of cone bipolar cells (CBCs) and compare their structural arrangements across bipolar types and postsynaptic partners. Three presynaptic configurations emerge—single-ribbon, ribbonless, and multiribbon synapses. Each CBC type exploits these arrangements in a unique combination, a feature also found among rabbit ON CBCs. Though most synapses are dyads, monads and triads are also seen. Altogether, mouse CBCs exhibit at least six motifs, and each CBC type uses these in a stereotypic pattern. Moreover, synapses between CBCs and particular partner types appear biased toward certain motifs. Our observations reveal synaptic strategies that diversify the output within and across CBC types, potentially shaping the distinct functions of retinal microcircuits.

The item count technique (ICT-MLE) regression model for survey list experiments depends on assumptions about responses at the extremes (choosing no or all items on the list). Existing list experiment best practices aim to minimize strategic misrepresentation in ways that virtually guarantee that a tiny number of respondents appear in the extrema. Under such conditions both the “no liars” identification assumption and the computational strategy used to estimate the ICT-MLE become difficult to sustain. I report the results of Monte Carlo experiments examining the sensitivity of the ICT-MLE and simple difference-in-means estimators to survey design choices and small amounts of non-strategic respondent error. I show that, compared to the difference in means, the performance of the ICT-MLE depends on list design. Both estimators are sensitive to measurement error, but the problems are more severe for the ICT-MLE as a direct consequence of the no liars assumption. These problems become extreme as the number of treatment-group respondents choosing all the items on the list decreases. I document that such problems can arise in real-world applications, provide guidance for applied work, and suggest directions for further research.

This article reports on a study in which, for five weeks, the English lessons of two classes of 11–12 year olds in Sweden were based on Roald Dahl’s Fantastic Mr Fox. To promote the learners’ engagement with the text, support understanding, and facilitate incidental vocabulary acquisition, a range of language-focused tasks were designed within the framework of the Storyline approach. In Storyline, a fictive world is created in the classroom. The story develops when learners, working in the same small groups, collaborate on open so-called key questions, which structure the Storyline, introduce happenings and problems, and link with the syllabus. Another characteristic is the integration of practical and theoretical subject content. Learners’ art work and texts are displayed on a frieze, or walls of the classroom, creating a visual record of the developing story. The study also investigated the influence on learning of the book’s illustrations, and the learners’ own drawings. The majority of the learners made gains in vocabulary, as evidenced in pre- and post-tests, writing and speaking tasks. While some learners had never thought about illustrations and drawings as a support, for many, both of these were found to be helpful.

Several recent studies link rising income inequality in the United States to the global financial crisis, arguing that US politicians did not respond to growing inequality with fiscal redistribution. Instead, Americans saved less and borrowed more to maintain relative consumption in the face of widening economic disparities. This article proposes a theory in which fiscal redistribution dampens the willingness of citizens to borrow to fund current consumption. A key implication is that pretax inequality will be more tightly linked with credit in less redistributive countries. The long-run partisan composition of government is, in turn, a key determinant of redistributive effort. Examining a panel of eighteen OECD democracies, the authors find that countries with limited histories of left-wing participation in government are significantly more likely see credit expansion as prefisc inequality grows compared to those in which the political left has been more influential.

Several recent studies link rising income inequality in the United States to the global financial crisis, arguing that US politicians did not respond to growing inequality with fiscal redistribution. Instead, Americans saved less and borrowed more to maintain relative consumption in the face of widening economic disparities. This article proposes a theory in which fiscal redistribution dampens the willingness of citizens to borrow to fund current consumption. A key implication is that pretax inequality will be more tightly linked with credit in less redistributive countries. The long-run partisan composition of government is, in turn, a key determinant of redistributive effort. Examining a panel of eighteen OECD democracies, the authors find that countries with limited histories of left-wing participation in government are significantly more likely see credit expansion as prefisc inequality grows compared to those in which the political left has been more influential.

A conformationally flexible template for the meta-C-H olefination of benzoic acids was designed through both experimental and computational efforts. The newly designed template favors a silver-palladium heterodimer low barrier transition state, and demonstrates that it is feasible to lengthen templates so as to achieve meta-selectivity when the distance between the functional handle of the native substrate and target C-H bond decreases. Analysis of the ortho-, meta-, and para-C-H cleavage transition states determined that the new template conformation optimizes the interaction between the nitrile and palladium-silver dimer in the meta-transition state, enabling palladium to cleave meta-C-H bonds with moderate-to-good yields and generally high regioselectivity. Regioselectivity is governed exclusively by the template, and kinetic experiments reveal that there is a 4-fold increase in rate in the presence of monoprotected amino acid ligands. Using a Boltzmann distribution of all accessible C-H activation transition states, it is possible to computationally predict meta-selectivity in a number of investigated templates with reasonable accuracy. Structural and distortion energies reported may be used for the further development of templates for meta-C-H activation of hitherto unexplored arene substrates.

Decades of research across several disciplines have produced substantial evidence that labor unions, on balance, reduce economic disparities. But unions are complicated, multifaceted organizations straddling markets and politics. Much of their equality-promoting influence occurs through their ability to reduce class-based inequity in politics and public policy. Declining unionization across much of the developed world is eroding workers’ bargaining power. Reduced economic leverage puts pressure on union solidarity and weakens labor-based political movements. Important research design problems and significant heterogeneity across unions, regions, countries, and time imply a continued need for more work.

Overcoming the reluctance of teenage learners to speak in the language classroom is a challenge for many teachers. This article reports on a study in which 60 Swedish pupils, aged 15-16, took part in a Storyline project based on a young adult fantasy novel. In the Storyline approach, a fictive world is created when learners, taking on the roles of characters in a story, collaborate on tasks to develop the story. A?key feature is that the learners work in the same small groups for much of the time. During the six-week period of this study, these learners used English in a variety of speaking and writing tasks. The project showed a number of benefits, the most important of which were an increase in their motivation to speak English and enhanced self-confidence through doing so.

Developing efficient molecular water oxidation catalysts for artificial photosynthesis is a challenging task. Here the authors introduce a ruthenium based complex with negatively charged sulfonate groups to effectively drive water oxidation under both acidic and neutral conditions.

Objectives: The objective of this review of reviews was to identify the potentially modifiable barriers and facilitators to physical activity in people with a musculoskeletal condition to influence intervention development. Study design: A rapid review of reviews. Methods: The Cochrane library and PubMed Central were searched for reviews using pre-defined search terms and relevant synonyms for “physical activity”, “barriers” or “facilitators”, and “musculoskeletal condition”. The identified reviews were screened for inclusion by the principal investigator in line with recognised streamlining approaches for a rapid review. Only review papers investigating the barriers and facilitators to physical activity in adults with a musculoskeletal condition were included. A team of seven assessed the included reviews for identification of the barriers and facilitators to physical activity coded using the COM-B model of behaviour. Results: 503 reviews were identified with 12 included for analysis across a mix of conditions and designs (n = 2: qualitative; n = 6: quantitative; n = 4 mixed). A multitude of interrelated factors were identified across the COM-B components. The most prevalent factors included disease symptoms and physical function (physical capability), knowledge of the specific benefits of physical activity and knowing what to do (psychological capability), the accessibility of facilities and individualised programming (physical opportunity), tailored advice from healthcare professionals and peer support (social opportunity), beliefs about the benefits or harms of being active (reflective motivation) and having the self-efficacy to be active and experiencing positive emotions (automatic motivation). Conclusions: This review of reviews identified the complex nature of physical activity in people living with a musculoskeletal condition. The identified barriers and facilitators should be considered by intervention designers when developing behaviour change interventions for this population group.