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This article examines the relationship between the development of the labour aristocracy and Lenin’s theory of imperialism, and the impact of both on the political fissure in the European labour movement in the early years of the 20th century. However, given that the labour aristocracy developed much earlier in Britain, the connection between imperialism and the split in socialism is not as clear-cut as it was in other European imperialist countries. The article analyses the composition of the labour aristocracy, accounts for its development in the mid-19th century, and considers the relevance of Lenin’s theory in the British context.

This symposium, held in November 2023, marked the 90th anniversary of the year that the Marx Memorial Library and Workers’ School (MML) was formed in 1933. That was, of course, also the year in which Hitler came to power in Germany. Between March and October 1933, all over Germany, Nazi supporters publicly banned and burned books and writings proscribed as un-German — book burnings that were a symbolic prelude to the systematic persecution of Jews, Marxists, pacifists and politically so-called ‘undesirables’. That context was highly significant for the formation of the MML. The common thread throughout the symposium was fascism: what we can learn from different experiences of fascism and the fight against it. Having defined fascism theoretically, the symposium went on to explore experiences of fascism and popular front strategies in response in India, Germany and France. There are powerful implications for progressive struggles in the contemporary context.

This study aimed to describe how the current practice of peripherally inserted central catheter (PICC) use in hospitalized children aligns with the Michigan Appropriateness Guide for Intravenous Catheters (miniMAGIC) in Children recommendations, explore variation across sites, and describe the population of children who do not receive appropriate PICCs.A retrospective study was conducted at 4 children’s hospitals in the United States. Children with PICCs placed January 2019 to December 2021 were included. Patients in the NICU were excluded. PICCs were categorized using the miniMAGIC in Children classification as inappropriate, uncertain appropriateness and appropriate.Of the 6051 PICCs identified, 9% (n = 550) were categorized as inappropriate, 9% (n = 550) as uncertain appropriateness, and 82% (n = 4951) as appropriate. The number of PICCs trended down over time, but up to 20% of PICCs each year were not appropriate, with significant variation between sites. Within inappropriate or uncertain appropriateness PICCs (n = 1100 PICC in 1079 children), median (interquartile range) patient age was 4 (0–11) years, 54% were male, and the main reason for PICC placement was prolonged antibiotic course (56%, n = 611). The most common admitting services requesting the inappropriate/uncertain appropriateness PICCs were critical care 24%, general pediatrics 22%, and pulmonary 20%. Complications resulting in PICC removal were identified in 6% (n = 70) of inappropriate/uncertain PICCs. The most common complications were dislodgement (3%) and occlusion (2%), with infection and thrombosis rates of 1% (n = 10 and n = 13, respectively).Although the majority of PICCs met appropriateness criteria, a substantial proportion of PICCs were deemed inappropriate or of uncertain appropriateness, illustrating an opportunity for quality improvement.

A review of current writings on women, gender and feminism

Although next-generation per- and polyfluorinated substances (PFAS) were designed and implemented as safer and environmentally degradable alternatives to “forever” legacy PFAS, there is little evidence to support the actual transformation of these compounds and less evidence of the safety of transformed products in the environment. Multiple congeners of one such PFAS alternative, the chloro-perfluoropolyether carboxylates (Cl-PFPECAs), have been found in New Jersey soils surrounding a manufacturing facility. These compounds are ideal candidates for investigating environmental transformation due to the existence of potential reaction centers including a chlorinated carbon and ether linkages. Transformation products of the chemical structures of this class of compounds were predicted based on analogous PFAS transformation pathways documented in peer-reviewed literature. Potential reaction products were used as the basis for high-resolution mass-spectrometric suspect screening of the soils. Suspected transformation products of multiple congeners, the Cl-PFPECAs, including H-PFPECAs, epox-PFPECAs, and diOH-PFPECAs, were tentatively observed in these screenings. Although ether linkages have been hypothesized as potential reaction centers under environmental conditions, to date, no documentation of ether scission has been identified. Despite exhaustive scrutiny of the high-resolution data for our Cl-PFPECA-laden soils, we found no evidence of ether scission.

Touch associated with sleep (sleep-touch; reported physical contact during or shortly before/after sleep) is underexplored as a distinct contributor to affect regulatory processes associated with adult sleep. Given the affect-regulating effects of interpersonal touch, we theorized that among healthy co-sleeping adults, sleep-touch would add to sleep-related effects on affective “resetting,” resulting in the experience of calmer, more regulated states. We studied 210 married heterosexual couples (aged 20–67 years, 79% non-Hispanic white, 13% Latinx) assigned 14 days of twice-daily (morning/evening) sleep/mood diaries. Multilevel daily (within-couple) mediation analyses showed that as hypothesized, more reported sleep-touch was associated with happier/calmer and less angry/irritable morning mood. In turn, happier/calmer mood was associated with greater enjoyment of time with spouse (for both spouses). Sleep-touch also was linked directly to both evening positive spousal events and enjoyment ratings. Sleep-touch was associated indirectly with fewer negative spousal events and less spouse-related stress via less angry/irritable morning mood (both spouses). Further, wives’ sleep-touch was related to happier/calmer husband mood and evening enjoyment; husbands’ sleep-touch was unrelated to wives’ reports. All associations with sleep-touch were present while accounting for subjective sleep quality, prior evening mood, non-sleep-related physical affection, day in study, and weekend versus weekday. We speculate that among relatively healthy satisfied couples, physical touch during and surrounding sleep may add to sleep’s restorative and affect-regulatory functions, suggesting a pathway through which co-sleeping can improve affect regulation and ultimately relationships and health.

This article, based on the author’s Engels Memorial Lecture on 26 November 2020, examines the significance of Friedrich Engels’s seminal work on the origin of the family, the oppression of women and the relationship of both to the development of private property. While accepting his overall analysis and rejecting alternatives, the article questions the application of Engels’s theory to an understanding of the working-class family. It suggests a way in which this lacuna can be remedied from a Marxist perspective.

There has been extensive literature examining the efficacy of exercise interventions in the treatment of depression over the past few decades. However, there is ongoing debate regarding the optimal dosage and the implications of utilising physiotherapists for the management of clinically depressed adults using exercise has not been examined. This review aimed to examine the effectiveness of exercise as a treatment for depression (without comorbidities) and to determine the most effective dosage/mode to treat this population. This review strived to appraise the literature for a potential role for physiotherapists in depression management. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, a search for randomized controlled trials was conducted on the nine databases. All studies were appraised for quality using the Physiotherapy Evidence Database (PEDro) scale and Cochrane Risk of Bias Tool (RoB). Data was manually extracted, and pre- and post-intervention depression scores and program variables were analysed. Of the 5036 papers retrieved, 7 papers met this review’s inclusion criteria. The results of the meta-analysis reveal that exercise as a sole treatment and as an add-on is significantly effective in reducing depressive symptoms. The findings support the use of moderate intensity aerobic exercise for three sessions per week. Exercise was shown to significantly improve depressive symptoms in depressed adults. This review adds to the growing body of evidence regarding the important role of physiotherapists in the treatment of psychiatric disorders in the design and implementation of exercise interventions.

HighlightsThere is a wide variance in neonatal and pediatric vascular access workforce models, training, and competency assessments.Pain control during procedures is critical for children, yet it is not consistently used.Procedural support has shown improved patient outcomes, yet is not standardly used for every distressful procedure.Core standards are needed to ensure proper training and support for the pediatric and neonatal vascular access clinicians.Background:Despite evidence to support best practice in neonatal and pediatric venipuncture delivery and procedural support, there are inconsistencies in practice. To inform future research, education, and workforce innovation, the Association for Vascular Access Pediatric Special Interest Group (PediSIG) developed and undertook a survey to describe the current vascular access practice for clinicians caring for neonatal and pediatric patients.Objective:Describe the current state of workforce models, training, and clinical practices surrounding pediatric and neonatal vascular access.Design:Cross-sectional, electronic survey using convenience sampling.Settings:International clinicians who provide vascular access (peripheral intravenous catheter insertion, venipuncture for blood sampling) for neonatal and pediatric patients.Methods:An electronic survey was developed by the PediSIG. The survey covered workforce models, clinician training and competency, pain relief, procedural support, and device securement. The electronic survey was then distributed to the PediSIG membership and shared among several neonatal/pediatric email lists. Data were analyzed descriptively, with an exploration of association between clinical outcomes, workforce, and training.ResultsThere were 242 responses from 5 countries showing a wide variance of practice. Workforce models showed many different team names and responsibilities along with a variance of personnel and staffing hours. Clinician training was described as 4 hours or less by 44% (n= 69) of respondents. Less than half of the responses (47%; n= 99) reported having a formal procedure to escalate a patient to an expert care and not having a set number of max attempts before escalation. Only two-thirds (n= 115) of respondents said they had a standardized protocol for pain control and procedural support, with only 13% (n= 23) and 15% (n= 27), respectively, self-reporting that they always followed the protocol.ConclusionsThe respondents reported a wide variance in neonatal and pediatric vascular access procedures and the resources used to support this practice. Core standards need to be developed to help guide neonatal and pediatric clinicians and their institutions. The standards should encompass recommendations for workforce models, proper training, competency, insertion guidelines, pain control,

Dora Montefiore and Helen Crawfurd were both foundation members of the Communist Party. They had a long history of activism for many years. Both had played an important part in the women’s suffrage movement and were, in addition, active socialists well before the foundation of the CPGB in 1920. They were socialist feminists, but their contribution prior to 1920 and their role subsequently as active communists has been largely ignored.

Robin Page Arnot’s writings and his own life provide a remarkable insight into socialist and communist politics of the twentieth century. His work as a socialist educator remains to be researched, but this article shows that there is enough to say with certainty that his efforts in the field of Marxist education were pioneering. His reputation as a scholar in the service of the labour movement, in particular on behalf of Britain’s miners, remains unparalleled. His life and work as an active communist over many decades remain as a rich primary source for labour historians.James Klugmann was a leading Marxist scholar, communist educator and activist. He studied at Cambridge and was associated with the famous spy ring; he then worked for the Comintern in Paris, making links with communist students around the world, and as part of the Special Operations Executive during the Second World War. From 1946 to his death in 1977, he worked as a Communist Party official, edited Marxism Today, and wrote the first two volumes of the history of the CPGB; was an outstanding educator associated with the Marx Memorial Library; and a thinker trying to comes to terms with Stalinist crimes, the Cold War, and the new postwar developments and political tendencies.Andrew Rothstein’s role as a communist educator and propagandist is examined from the1920s to the 1980s. The article identifies his special contribution as bringing together an understanding of the revolutionary Bolshevik tradition of Russia and the anti-imperialist tradition of the British working class, and as carrying forward the legacy of his father Theodore within the Social Democratic Federation/British Socialist Party between 1890 and 1920. The article considers his achievement in combining the defence of Marxism as an integral component of Britain’s labour movement and Labour Party with his role as the British spokesperson for the world’s first socialist state from 1920 to the 1960s

•Daily nonrestorative sleep and activity interference are sequentially mediated.•Greater nonrestorative sleep is associated with higher morning pain catastrophizing.•Morning pain catastrophizing significantly predicts afternoon pain severity.•Higher afternoon pain severity is related to greater end-of-day activity interference.•Nonrestorative sleep and catastrophizing also uniquely predict activity interference.

In recent years, an increasing number of polymeric composites incorporating engineered nanomaterials (ENMs) have reached the market. Such nano-enabled products (NEPs) present enhanced performance through improved mechanical, thermal, UV protection, electrical, and gas barrier properties. However, little is known about how environmental weathering impacts ENM release, especially for high-tonnage NEPs like kaolin products, which have not been extensively examined by the scientific community. Here we study the simulated environmental weathering of different polymeric nanocomposites (epoxy, polyamide, polypropylene) filled with organic (multiwalled carbon nanotube, graphene, carbon black) and inorganic (WS2, SiO2, kaolin, Fe2O3, Cu-phthalocyanines) ENMs. Multiple techniques were employed by researchers at three laboratories to extensively evaluate the effect of weathering: ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), optical microscopy, contact angle measurements, gravimetric analysis, analytical ultracentrifugation (AUC), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Raman spectroscopy. This work aimed to elucidate the extent to which weathering protocol (i.e.wet vs.dry) and diverse filler characteristics modulate fragment release and polymer matrix degradation. In doing so, it expanded the established NanoRelease protocol, previously used for analyzing fragment emission, by evaluating two significant additions: (1) simulated weathering with rain events and (2) fractionation of sample leachate prior to analysis. Comparing different composite materials and protocols demonstrated that the polymer matrix is the most significant factor in NEP aging. Wet weathering is more realistic than dry weathering, but dry weathering seems to provide a more controlled release of material over wet. Wet weathering studies could be complicated by leaching, and the addition of a fractionation step can improve the quality of UV-vis measurements.

Per- and polyfluoroalkyl substances (PFAS) are globally distributed and potentially toxic compounds. We report accumulation of chloroperfluoropolyethercarboxylates (Cl-PFPECAs) and perfluorocarboxylates (PFCAs) in vegetation and subsoils in New Jersey. Lower molecular weight Cl-PFPECAs, containing 7–10 fluorinated carbons, and PFCAs containing 3–6 fluorinated carbons were enriched in vegetation relative to surface soils. Subsoils were dominated by lower molecular weight Cl-PFPECAs, a divergence from surface soils. Contrastingly, PFCA homologue profiles in subsoils were similar to surface soils, likely reflecting temporal-use patterns. Accumulation factors (AFs) for vegetation and subsoils decreased with increasing CF2, 6–13 for vegetation and 8–13 in subsoils. In vegetation, for PFCAs having CF2= 3–6, AFs diminished with increasing CF2as a more sensitive function than for longer chains. Considering that PFAS manufacturing has transitioned from long-chain chemistry to short-chain, this elevated vegetative accumulation of short-chain PFAS suggests the potential for unanticipated PFAS exposure levels globally in human and/or wildlife populations. This inverse relationship between AFs and CF2-count in terrestrial vegetation is opposite the positive relationship reported in aquatic vegetation suggesting aquatic food webs may be preferentially enriched in long-chain PFAS. AFs normalized to soil–water concentrations increased with chain length for CF2= 6–13 in vegetation but remained inversely related to chain length for CF2= 3–6, reflecting a fundamental change in vegetation affinity for short chains compared to long.

Herein, we report a case of a 9-yr-old girl who had a 46, XX peripheral karyotype and apparent developmentally normal ovaries. She presented with abdominal pain and a right adnexal mass. No clinical or pathologic evidence of gonadal dysgenesis or undifferentiated gonadal tissue was detected. She underwent right salpingo-oophorectomy with rupture of the tumor at the time of operation due to recent adnexal torsion. The original pathologic diagnosis was gonadoblastoma and mixed germ cell tumor. Most significantly in our study, we identified a rare and novel pathway for the development of malignant mixed germ cell tumor from gonadoblastoma in the absence of identifiable dysgerminoma. The histologically identifiable steps of progression in our case were as follows: (1) residual islands of classic gonadoblastoma, (2) overgrowth by “dissecting” gonadoblastoma composed of transformed germ cells with clear cytoplasm and sex cord elements surrounded by a basement membrane, (3) stromal infiltration by dedifferentiated germ cells with loss of basement membrane, (4) formation of malignant mixed germ cell tumor. The dedifferentiated areas were composed of anaplastic germ cells with amphophilic cytoplasm that gradually replaced the sex cord elements by clonal expansion. Both the original transformed and the anaplastic germ cell components strongly expressed OCT4. We believe that the mixed germ cell tumor arose from the dedifferentiated germ cell component through neoplastic progression. This premise suggests that the germ cell component of “dissecting” gonadoblastoma rarely undergoes anaplastic change in the absence of transition to germinoma and can be the direct precursor of mixed germ cell tumor.

BACKGROUND:Declining liver function is a concerning side effect associated with radiation therapy. Biomarkers of liver toxicity would be useful in personalizing therapy. METHODS:As part of two prospective clinical trials examining adaptive radiation therapy, we collected serum samples from patients receiving liver radiation. We performed a screen of 22 cytokines using a multiplex assay then used ELISA to quantify the cytokines of greatest interest. Subjects were split into screening and validation cohorts. Toxicity was defined as an increase in Child-Pugh score of 2 points or greater within 6 months. Logistic regression models were used to estimate the relationship between our toxicity endpoint and serum cytokine concentrations. RESULTS:Our initial screen (46 subjects, 11 events) identified hepatocyte growth factor (HGF), CD40L (CD154), and eotaxin (CCL11) as potentially predictive of toxicity. We then tested these markers in an expanded patient cohort (104 subjects, 18 events) with a batch correction due to varying age of the samples which confirmed that high HGF and low CD40L were associated with a subsequent decline in liver function following radiation therapy. Multivariate analysis factoring in baseline Child-Pugh score and mean liver radiation dose demonstrated that HGF and CD40L were potentially predictive of toxicity (HGF OR 4.3, P = .009; CD40L OR 0.5 P = .06). Additionally, higher than median baseline HGF levels (1.4 ng/ml) were significantly associated with decreased survival following liver radiation (27.1 vs 14.5 months, P = .03). CONCLUSIONS:Our study identifies high HGF and low CD40L as potential markers of liver toxicity following radiation therapy.

Lamisil (terbinafine) is an effective, widely prescribed antifungal drug that causes rare idiosyncratic hepatotoxicity. The proposed toxic mechanism involves a reactive metabolite, 6,6-dimethyl-2-hepten-4-ynal (TBF-A), formed through three N-dealkylation pathways. We were the first to characterize them using in vitrostudies with human liver microsomes and modeling approaches, yet knowledge of the individual enzymes catalyzing reactions remained unknown. Herein, we employed experimental and computational tools to assess terbinafine metabolism by specific cytochrome P450 isozymes. In vitroinhibitor phenotyping studies revealed six isozymes were involved in one or more N-dealkylation pathways. CYP2C19 and 3A4 contributed to all pathways, and so, we targeted them for steady-state analyses with recombinant isozymes. N-Dealkylation yielding TBF-A directly was catalyzed by CYP2C19 and 3A4 similarly. Nevertheless, CYP2C19 was more efficient than CYP3A4 at N-demethylation and other steps leading to TBF-A. Unlike microsomal reactions, N-denaphthylation was surprisingly efficient for CYP2C19 and 3A4, which was validated by controls. CYP2C19 was the most efficient among all reactions. Nonetheless, CYP3A4 was more selective at steps leading to TBF-A, making it more effective in terbinafine bioactivation based on metabolic split ratios for competing pathways. Model predictions did not extrapolate to quantitative kinetic constants, yet some results for CYP3A4 and CYP2C19 agreed qualitatively with preferred reaction steps and pathways. Clinical data on drug interactions support the CYP3A4 role in terbinafine metabolism, while CYP2C19 remains understudied. Taken together, knowledge of P450s responsible for terbinafine metabolism and TBF-A formation provides a foundation for investigating and mitigating the impact of P450 variations in toxic risks posed to patients.

•HLA-DRB1*15:01and the genetic risk score for MS contributes to early age of onset.•MS genetic risk component does not contribute to other aspects of onset.•Obesity and smoking status modulates MS presentation.

Several studies have analyzed the ice margin behavior of the Quelccaya Ice Cap (QIC), Earth's largest tropical ice cap, through the Holocene. However, continuous integration of new information to produce a more cohesive history of the QIC is necessary. Here, the radiocarbon dates of 33 rooted plant specimens collected in situ along the western ice margin between 2002 and 2018 reveal the timing of its past extent as it advanced during the mid‐Holocene. The most recent evaluation of collected specimens indicates that the QIC margin advanced ∼350 m down the Challpacocha Valley between 7.1 and 4.5 ka BP. Past studies of documented ice extent on the western side of the QIC based on a variety of techniques are compiled to create a more comprehensive history of the QIC's behavior throughout the Holocene. Records of documented ice extent, as well as other proxy records, indicate a climate transition ∼5–7 ka BP that created the proper environmental conditions for the expansion of the QIC. Evidence from nearby valleys indicates that the QIC behaved similarly to the documented ice extent in the Challpacocha Valley in response to Holocene climatic fluctuations. The ability to collect the plant specimens and recent analysis of satellite imagery reveals rapid retreat rates of the western outlet glaciers from 1985 to 2020, leaving the western margin of the QIC at its smallest extent since the mid‐Holocene. The area around the Quelccaya Ice Cap (QIC) is unique as wetland plant samples have been found preserved in their growth positions, buried by past advancing ice, whereas the ice typically removes vegetation and soil in its advance down a valley. Using the 14C dates of these plants, we map a 350‐m advance of the ice margin between 7.1 and 4.5 ka BP. Combined with a variety of previous studies involving different methods and records from ice and lacustrine sediment cores, a larger picture of the QIC's behavior comes into view. A largely accepted global climate shift between ∼7 and 5 ka BP occurred in tandem with the QIC's advance. Although the QIC has fluctuated before, at no time has the western margin receded to the current extent since the mid‐Holocene. This is indicated by the exposure of the plants and current margin retreat rates calculated from satellite imagery (1985–2020). Mid‐Holocene advance of the Quelccaya Ice Cap (QIC) is documented using 14C dating of in situ vegetation exposed during the recent retreatPlant ages of ∼4.5 to ∼7.1 ka BP provide evidence of a mid‐Holocene climate transition and the QIC ice‐margin expansionAnalysis of satellite imagery from 1985 to 2020 documents a recent rapid retreat (∼20 m/yr) of the QIC margin Mid‐Holocene advance of the Quelccaya Ice Cap (QIC) is documented using 14C dating of in situ vegetation exposed during the recent retreat Plant ages of ∼4.5 to ∼7.1 ka BP provide evidence of a mid‐Holocene climate transition and the QIC ice‐margin expansion Analysis of satellite imagery from 1985 to 2020 documents a recent rapid retreat (∼20 m/yr) of the QIC margin

Background:Central-line–associated bloodstream infection (CLABSI) rates have steadily decreased as evidence-based prevention bundles were implemented. Bone marrow transplant (BMT) patients are at increased risk for CLABSI due to immunosuppression, prolonged central-line utilization, and frequent central-line accesses. We assessed the impact of an enhanced prevention bundle on BMT nonmucosal barrier injury CLABSI rates. Methods:The University of Iowa Hospitals & Clinics is an 811-bed academic medical center that houses the only BMT program in Iowa. During October 2018, we added 3 interventions to the ongoing CLABSI prevention bundle in our BMT inpatient unit: (1) a standardized 2-person dressing change team, (2) enhanced quality daily chlorhexidine treatments, and (3) staff and patient line-care stewardship. The bundle included training of nurse champions to execute a team approach to changing central-line dressings. Standard process description and supplies are contained in a cart. In addition, 2 sets of sterile hands and a second person to monitor for breaches in sterile procedure are available. Site disinfection with chlorhexidine scrub and dry time are monitored. Training on quality chlorhexidine bathing includes evaluation of preferred product, application per product instructions for use and protection of the central-line site with a waterproof shoulder length glove. In addition to routine BMT education, staff and patients are instructed on device stewardship during dressing changes. CLABSIs are monitored using NHSN definitions. We performed an interrupted time-series analysis to determine the impact of our enhanced prevention bundle on CLABSI rates in the BMT unit. We used monthly CLABSI rates since January 2017 until the intervention (October 2018) as baseline. Because the BMT changed locations in December 2018, we included both time points in our analysis. For a sensitivity analysis, we assessed the impact of the enhanced prevention bundle in a hematology-oncology unit (March 2019) that did not change locations. Results:During the period preceding bundle implementation, the CLABSI rate was 2.2 per 1,000 central-line days. After the intervention, the rate decreased to 0.6 CLABSI per 1,000 central-line days (P= .03). The move in unit location did not have a significant impact on CLABSI rates (P= .85). CLABSI rates also decreased from 1.6 per 1,000 central-line days to 0 per 1,000 central-line days (P< .01) in the hematology-oncology unit. Conclusions:An enhanced CLABSI prevention bundle was associated with significant decreases in CLABSI rates in 2 high-risk units. Novel infection prevention bundle elements should be considered for special populations when all other evidence-based recommendations have been implemented.Funding:NoneDisclosures:None

Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results1,2, and 1 in 50 experiences drug-induced liver injury3. Since genomic variation contributes to other forms of drug-induced liver injury4,5, we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P=2.3 × 10–8, odds ratio = 8.3, 95% confidence interval = 3.6–19.2). Analysis of an independent cohort of IFN-β-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P=7.6 × 10–5) and alkaline phosphatase (P=4.9 × 10-4). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use.

High-elevation tropical glaciers provide records of past climate from which current changes can be assessed. Comparisons among three ice-core records from tropical mountains on opposite sides of the Pacific Ocean reveal how climatic events are linked through large-scale processes such as El Niño–Southern Oscillation. Two distinctive trans-Pacific events in the mid-fourteenth and late-eighteenth centuries are distinguished by elevated aerosol concentrations in cores from the Peruvian Andes and the Tibetan Himalaya. Today aerosol sources for these areas are enhanced by droughts accompanying El Niñños. In both locations, large-scale atmospheric circulation supports aerosol transport from likely source regions. Oxygen isotopic ratios from the ice cores are significantly linked with tropical Pacific sea-surface temperatures, especially in the NIññÑO3.4 region. The arid periods in the fourteenth and eighteenth centuries reflect droughts that were possibly connected to strong and/or persistent El NiññÑño conditions and Intertropical Convergence Zone migration. These ‘black swans’ are contemporaneous with climate-related population disruptions. Recent warming, particularly at high elevations, is posing a threat to tropical glaciers, many of which have been retreating at unprecedented rates over the last several thousand years. The diminishing ice in these alpine regions endangers water resources for populations in South Asia and South America.

Chest tubes are utilized to evacuate shed blood after left ventricular assist device (LVAD) implantation, however, they can become clogged, leading to retained blood. We implemented a protocol for active tube clearance (ATC) of chest tubes to determine if this might reduce interventions for retained blood. A total of 252 patients underwent LVAD implantation. Seventy-seven patients had conventional chest tube drainage (group 1), whereas 175 patients had ATC (group 2). A univariate and multivariate analysis adjusting for the use of conventional sternotomy (CS) and minimally invasive left thoracotomy (MILT) was performed. Univariate analysis revealed a 65% reduction in re-exploration (43–15%, p< 0.001), and an 82% reduction in delayed sternal closure (DSC; 34–6%, p<0.001). In a sub-analysis of CS only, there continued to be statistically significant 53% reduction in re-exploration (45% vs.21%, p= 0.0011), and a 77% reduction in DSC (35% vs. 8%, p< 0.001) in group 2. Using a logistic regression model adjusting for CS versusMILT, there was a significant reduction in re-exploration (odds ratio [OR] = 0.44 [confidence interval {CI} = 0.23–0.85], p= 0.014) and DSC (OR = 0.20 [CI = 0.08–0.46], p<0.001) in group 2. Actively maintaining chest tube patency after LVAD implantation significantly reduces re-exploration and DSC.

As ventricular-assist devices (VADs) are increasingly employed in heart failure management, a leading cause of mortality, new literature is consistently published on less-invasive implantation techniques. Although early perioperative outcomes have been shown to be favorable with minimally invasive left thoracotomy (LT) approaches compared with conventional sternotomy (CS), studies comparing long-term outcomes are lacking. We set out to evaluate long-term follow up between LT and CS approach. In a single center, retrospective review, data on patients with similar demographic profiles were collected. HeartWare (HVAD) implantation was performed by either CS or LT. Analysis was performed on perioperative adverse outcomes, and 6 month postoperative adverse events. Primary objectives of the study included comparative outcomes of morbidity and mortality between both groups at 180 days postimplantation. Eighty-one (n = 81) bridge to transplant (BTT) patients underwent CS or LT HVAD implantation. Perioperative transfusion (p= 0.04) favored the LT cohort compared with CS, with a median of 6 units and 8 units transfused for each group, respectively. No survival difference was observed between both groups at 6 months postimplantation (p= 0.52). Clinical outcomes at an average of 6 month follow up showed no difference in adverse events, including common postoperative VAD complications such as infection and right heart failure. Miniaturization of LVAD size and improvement in technology has allowed expansion of interest in alternative surgical approaches for HVAD implantation. For BTT patients, no difference in early outcome was observed 6 months after implantation using a left LT versusCS technique.

Cell expansion techniques commonly utilize exogenous factors to increase cell proliferation and create a larger cell population for use in cell-based therapies. One strategy for cartilage regenerative therapies is autologous stem cell expansion and fibroblast growth factor (FGF) supplementation during cell expansion, particularly FGF-2. However, it is unknown whether FGF-10, another FGF implicated in limb and skeletal development, can elicit the same rejuvenation responses in terms of proliferation and differentiation of human synovium-derived stem cells (SDSCs). In this study, we expanded SDSCs in either FGF-2 or FGF-10 for 7 days; a control group had no treatment. FGF-2 and FGF-10 supplementation was also exclusively tested during the differentiation phase. Expanded SDSCs were evaluated for their ability to successfully engage in chondrogenic and osteogenic differentiation. We found that FGF-2 supplementation during proliferation, but not differentiation, was able to increase glycosaminoglycan deposition, pellet size, and chondrogenic gene expression following chondrogenic induction, as well as increased calcium deposition, alkaline phosphatase activity, and expression of vital osteogenic differentiation genes following osteogenic induction. FGF-10 did not elicit a similar preconditioning effect. We also observed changes of both Wnt signals and mitogen-activated protein kinase expression during SDSC chondrogenesis, which occurred in a manner dependent upon the supplementation phase of FGF-2 administration. These results indicated that FGF-2, but not FGF-10, may be supplemented during stem cell expansion to prime cells for successful chondrogenesis and osteogenesis.

Guidelines for performing concomitant procedures (CPs) in patients undergoing continuous flow-left ventricular assist device (CF-LVAD) implantation are unclear. The impact of an increased surgical complexity outside the constraint of landmark clinical trials has not been reported. From May 2004 to December 2013, 614 patients (499 males, 81%) underwent CF-LVAD implant at our institutions. Median age was 57 ± 13 years and 364 (59%) were bridge to transplantation (BTT). Survival and device-related complications were analyzed and stratified based on the surgical intervention. A total of 398 patients (65%) underwent CF-LVAD implantation without CPs. The remaining patients (35%, n = 216) were grouped according to various CPs. Survival was comparable between groups and not influenced by the CP, device type, or indication for implant. Time-to-first device-related adverse event was shorter in patients with CPs. Regression analysis revealed only increased age (p= 0.03), increase in baseline creatinine (p= 0.002), cardiopulmonary bypass time (p= 0.03), and decreased body mass index (p= 0.03) were predictors of mortality, whereas only age (p= 0.006) and prior sternotomy (p= 0.02) were related to adverse device-related events. Performing CPs leads to comparable survival and device-related outcomes after implant. The decision to perform CPs should be balanced with age, preoperative renal dysfunction, and projected complexity of surgery.

The HeartWare ventricular assist device (HVAD) is an implantable continuous-flow centrifugal pump that has allowed the development of sternal-sparing techniques, with the use of alternative outflow strategies. We compared early outcomes for patients bridged with the conventional versusalternative outflow graft strategy. From January 2013 to October 2014, 89 patients with HVAD implantation were identified. Survival was analyzed with Kaplan–Meier methods, and a log-rank test was used to compare outcomes between groups. Thirty patients (34%) had ≥1 previous sternotomy before HVAD implantation. Eight patients (27%) were approached using an alternative outflow graft technique with outflow graft connection to the descending aorta (n = 4, 50%) or left subclavian artery (n = 4, 50%), whereas 22 (73%) were implanted viaa conventional sternotomy approach with the outflow graft to the ascending aorta. Preoperative characteristics (age, Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and Lietz-Miller score) were comparable between groups (all p> 0.05). Median follow-up was 4.7 (2.8–9.3) months of support. Outcomes were comparable between conventional and alternative outflow groups; survival at 6 months was 74% for the conventional group and 83% in the alternative outflow group. An alternative outflow graft strategy can be utilized to support bridged patients with a history of prior sternotomy.

Driveline infections (DLI) are a cause of morbidity after continuous-flow left ventricular assist device (CF-LVAD) implantation. Because driveline trauma contributes to DLI, we assessed whether intraoperative placement of a temporary external anchoring suture (EAS) influenced DLI rate. We analyzed 161 consecutive patients with CF-LVAD (HMII 82; HW 79) implantation. Two groups were defined: placement of EAS (n = 85) or No EAS (n = 76). For NO EAS patients, the driveline was permanently anchored internally to the rectus fascia. Cox proportional analysis was performed to assess the effect of EAS on time to first confirmed DLI. Baseline characteristics were comparable between groups (all p= 0.3). Mean follow-up time was 0.93 years. A total of 18 (11.1%) patients developed confirmed culture positive DLI, with “first infection” rate of 0.13 events/year. Mean time to confirmed DLI was 0.69 years. Driveline infection was less likely (hazard ratio [HR] = 0.28, 0.95 confidence interval [CI] = 0.06–1.25, p= 0.056) to occur in NO EAS (2/18) then in EAS (16/18). Confirmed DLI was comparable between device types (p= 0.3). Multivariable regression adjusted for age, BMI, blood product use, device type, and diabetes showed equivocal effect of EAS (HR = 0.33, 0.95 CI = 0.07–1.54, p= 0.12). Patients with a temporary EAS may have an increased risk of confirmed DLI after device implantation.

The concept of biventricular support with durable centrifugal pumps is evolving, and the surgical strategy and best practice guidelines for implantation of right-sided devices are still unknown. We present optimal strategy for bilateral HeartWare continuous-flow ventricular assist device (HVAD) implantation in a series of four patients. Patients were implanted with the HVAD pumps simultaneously or sequentially. This report offers a perspective on surgical considerations such as right ventricular positioning, implications related to potential risks of obstruction from the tricuspid apparatus, the role if any of downsizing the outflow anastomosis, and considerations for speed adjustments. In this series, one patient died on support and three patients experienced pump thrombosis requiring device revision. All other patients survived until orthotopic heart transplantation, although one of these patients died from perioperative complications, 2 days posttransplantation. Surgical management of patients with medically refractory biventricular heart failure remains challenging and associated with a high incidence of pump thrombosis. Best practice guidelines from experts’ consensus are still needed to address this challenging population.

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Emergency general surgery (EGS) is defined as the urgent assessment and treatment of non-trauma, general surgical emergencies involving adults. Acute surgical emergencies often represent the most common reason for hospital admission with diagnoses, including bowel obstruction and appendicitis. EGS is a growing surgical subspecialty that includes both operative and nonoperative management of acutely ill patients. We sought to assess the burden of nonoperative care in EGS patients at our academic medical center. This study was conducted by retrospective analysis of prospectively collected data from patients entered into the Duke EGS Registry between July 1, 2016 and September 10, 2017. Fifty-six per cent (n = 771) of patients in the Duke EGS Registry (n = 1377) were managed nonoperatively as compared with 44 per cent (n = 606) who were managed operatively. Nonoperative management of disease represents a large subset of EGS and, therefore, needs further investigation to improve processes, outcomes, and standardization of care.