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Background Anthracycline-related cardiac dysfunction is a recognised consequence of cancer therapies. Here we assess resting cardiac and skeletal muscle energic status as an early mechanistic pathway of myocyte derangement and explore molecular targets of skeletal myocyte metabolism, protein synthesis/degradation and mitochondrial biogenesis signalling. Methods We conducted a prospective, mechanistic, observational, longitudinal study of chemotherapy-naive breast cancer patients undergoing anthracycline-based chemotherapy, compared to a healthy control group. 31P-Magnetic Resonance spectroscopy in cardiac and skeletal muscle (phosphocreatine/gamma adenosine triphosphate (PCr/yATP) and inorganic phosphate/phosphocreatine (Pi/PCr) ratios respectively), cardiac magnetic resonance (CMR) imaging inclusive of T1 and T2 mapping, echocardiography-derived global longitudinal strain function, serum NT-pro-BNP and skeletal muscle biopsies from the right vastus lateralis were assessed before and after 3 cycles of Flurouracil, Epirubicin and Cyclophosphamide followed by 3 cycles of Docetaxel. Statistical significance was set at p Results Twenty-five female breast cancer patients (median age 53 years, range 32–74 years) receiving a mean epirubicin dose 307 mg/m2) and twenty-eight controls (median age 44 years, range 23–65) were recruited. All study assessments in breast cancer patients at pre-chemotherapy stage were comparable to the matched healthy controls. However, following chemotherapy, breast cancer patients demonstrated a small but significant reduction in cardiac function (global longitudinal strain −22.9±3.9 vs −19.1±3.3%, p=0.01 and CMR-derived ejection fraction 65±5 vs 62±4%, p=0.047), a mild increase in CMR-derived indexed left ventricular volumes (end diastolic 65±10 vs 74±11 ml/m2, p=0.014 and end systolic 23±5 vs 28±5 ml/m2, p=0.01) as well as an increase in left ventricular T1 and T2-mapping (1289±29 vs 1321±31 ms, p=0.004 and 50±4 vs 55±7 ms, p=0.027, respectively) and serum NT-Pro-BNP (49±25 vs 108±84 pg/m, p=0.008). After epirubicin, there was significant reduction in cardiac PCr/yATP ratio (2.0±0.7 vs 1.2±0.6, p=0.007) and a significant increase in skeletal muscle Pi/PCr ratio (0.13±0.04 vs 0.22±0.2, p=0.008) – Figure 1. Following chemotherapy, there was significant upregulation of skeletal myocyte protein synthesis (mammalian target of rapamycin, 0.44±0.4 vs 0.53±0.2, p Conclusion Contemporary doses of epirubicin for breast cancer result in significant reduction of cardiac and skeletal muscle high energy 31P-metabolism alongside skeletal myocellular alterations of protein synthesis and metabolic regulation pathways. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Tenovus ScotlandNHS Grampian Endowment fund

The present study was designed to test the hypothesis that there was no association between initial opioid prescription size and the likelihood of refill after elective primary total knee (TKA) and hip arthroplasty (THA).We retrospectively analyzed large national datasets of commercial and Medicare insurance claims to identify a weighted cohort of 120,889 primary total joint arthroplasties (76,900 TKA and 43,989 THA) comprised of opioid-naive patients aged 18 to 75 years who had surgery between January 2015 and November 2019. The primary outcome was refill of any prescription opioid medication within 30 days after discharge, and the primary predictor variable was the total amount of opioid filled in the initial discharge prescription measured in oral morphine equivalents (OMEs). Logistic regressions were used to estimate the likelihood of refill, given a particular prescription size while adjusting for multiple patient factors, including age, sex, comorbidities, and year of surgery.The 30-day refill rate was 59.6% following TKA and 26.1% for THA. Adjusted odds of refill decreased by 2% for every 75 OME (10 tablets of 5 mg oxycodone) increase to the initial prescription size among the THA cohort (adjusted odds ratio [OR] = 0.98; 95% CI 0.97-0.99), and decreased by 3% for the TKA cohort (aOR = 0.97; 95% CI 0.97-0.98).These nationally representative data demonstrated that larger initial opioid prescription size was associated with small but clinically insignificant decreases in 30-day refill after total joint arthroplasty. This finding should allay concerns about efforts to decrease postsurgical opioid prescribing.

Aim The PREDICT score is used to help define decisions about benefits of chemotherapy in early invasive breast cancer. With a PREDICT score of 5% or more chemotherapy should be considered, 3% to 4% is a borderline decision and less than 3% chemotherapy is not pursued. We set out to compare the PREDICT score to Oncotype Dx recurrence score (RS), which predicts chemotherapy benefit based on 21-gene breast cancer assay. Method Data for patient and tumour characteristics, and treatment choice was collected from electronic patient records of 98 patients who had an RS score done between February 2017-September 2020. This data was then compared to the patients’ PREDICT scores. Results 98 patients were analysed with 2 excluded due to having nodal macro-metastases. Mean patient age was 53 years with an average tumour size of 27mm. 31/96 (32%) patients had a PREDICT score ≥5%, with 21/31 (68%) having a low RS score ( Conclusions 68% of patients in the ≥5% PREDICT group had a low RS score and so have avoided chemotherapy. In the 3-4% group, approximately 1 in 3 tested were shown to have a chemotherapy benefit. In the

Objective Most studies on preoperative opioid use only describe whether or not patients use opioids without characterizing reasons for use. Knowing why patients use opioids can help inform perioperative opioid management. The objective of this study was to explore pain specific reasons for preoperative opioid use prior to total hip and knee arthroplasty (THA and TKA) and their association with persistent use. Methods This is a prospective study of 197 patients undergoing THA (n = 99) or TKA (n = 98) enrolled in the Analgesic Outcomes Study between December 2015 and November 2018. All participants reported preoperative opioid use. Results Reasons for preoperative opioid use were categorized as surgical site pain only (81 [41.1%]); pain in other body areas only (22 [11.2%]); and combined pain (94 [47.7%]). Compared to patients taking opioids for surgical site pain, those with combined reasons for use had 1.24 (P = .40) and 2.28 (P = .16) greater odds of persistent use at 3 and 6 months postoperatively, adjusting for relevant covariates. Conclusions This study provides novel insights into the heterogeneity of reasons for presurgical opioid use in patients undergoing a THA or TKA. One key take away is that not all preoperative opioid use is the same and many patients are taking opioids preoperatively for more than just pain at the surgical site. Combined reasons for use was associated with long-term use, suggesting nonsurgical pain, in part, drives persistent opioid use after surgery. Future directions in perioperative care should focus on pain and non-pain reasons for presurgical opioid use to create tailored postoperative opioid weaning plans.

The purpose of this study was to determine whether male patients taking pre-operative selective alpha-1 adrenergic blocking agents have a lower likelihood of developing post-operative urinary retention (POUR) and a shorter length of hospitalization following lower extremity arthroplasty. A retrospective cohort study was conducted of patients who underwent primary or revision total hip or knee arthroplasty, or unicompartmental knee arthroplasty at an academic institution from January 2002 to May 2014. A cohort of male patients aged 35 and older who were taking a selective alpha-1 blocker prior to surgery (N = 229) were compared with a control group (N = 330) not taking one of these medications. Propensity score–matched logistic regression was performed to isolate the effect of taking a selective alpha-1 blocker on POUR. When evaluating for the outcome of POUR while controlling for age, hypertension, benign prostatic hyperplasia, urinary tract infections, type of anaesthesia, and procedure, those patients taking an alpha-1 blocker had a 12.1% decreased relative risk (95% CI 3.4 to 20.8%; p = 0.007) of developing POUR compared with patients not taking these medications. Mean length of stay was 3.8 days (95% CI 3.6 to 4.1) in the cohort taking selective alpha-1 blockers compared with 4.7 days (95% CI 4.4 to 4.9) for the control cohort. After controlling for known risk factors for the development of POUR, the use of selective alpha-1 blockers pre-operatively reduces the risk of developing urinary retention after lower extremity arthroplasty and is associated with a 1-day decreased length of stay.

OBJECTIVE: Determine preoperative patient characteristics associated with postoperative outpatient opioid use and assess the frequency of postoperative opioid overprescribing. SUMMARY BACKGROUND DATA: Although characteristics associated with inpatient opioid use have been described, the patient factors associated with opioid use after discharge are unknown but could inform the development of individualized approaches to postoperative prescribing. METHODS: We included opioid-naïve patients undergoing hysterectomy, thoracic surgery, and total knee and hip arthroplasty in a single-center prospective observational cohort study. Preoperative phenotyping included self-report measures to assess pain severity, fibromyalgia survey criteria score, pain catastrophizing, depression, anxiety, functional status, fatigue, and sleep disturbance. Our primary outcome measure was self-reported total opioid use in oral morphine equivalents (OMEs). We constructed multivariable linear regression models predicting opioids consumed in the first postoperative month. RESULTS: We enrolled 1,181 patients; 1,001 had complete primary outcome data and 913 had complete phenotype data. Younger age, non-Caucasian race, lack of a college degree, higher anxiety, greater sleep disturbance, heavy alcohol use, current tobacco use, and larger initial opioid prescription size were associated with increased opioid consumption. Median total OMEs prescribed was 600 (equivalent to 120 5-mg hydrocodone pills), while median opioid consumption was 188 OMEs (38 pills). CONCLUSIONS: In this prospective cohort of opioid-naïve patients undergoing major surgery, we found a number of characteristics associated with greater opioid use in the first month after surgery. Future studies should address the use of non-opioid medications and behavioral therapies in the perioperative period for these higher risk patients.

Background Postoperative urinary retention (POUR) is common. Selective alpha-1 adrenergic antagonists, such as tamsulosin, are effective for treating urinary retention. The purpose of this study is to determine whether perioperative prophylactic tamsulosin reduces the incidence of POUR following total hip and knee arthroplasty. Methods Male patients 35 years of age and older undergoing primary total hip or knee arthroplasty at a single center from 2015 to 2018 were eligible for inclusion. Patients were randomized to receive tamsulosin 0.4 mg or placebo daily for 5 days preoperatively, the morning of surgery, and the first postoperative day. The incidence of POUR was determined during the postoperative hospitalization. Results A total of 176 patients were enrolled in the study. Two patients were withdrawn prior to randomization. The remaining 174 were randomized to tamsulosin (n = 87) or placebo (n = 87). After an additional 43 patients were withdrawn prior to surgery, 131 patients completed the study (tamsulosin, n = 64; placebo, n = 67). A total of 42 patients (32.1%) developed POUR, with 18 cases (28.1%) in the tamsulosin group and 24 cases (35.8%) in the placebo group (P = .345), resulting in an odds ratio of 0.701 and a risk difference of 7.69%. Conclusion Prophylactic tamsulosin did not reduce the incidence of POUR after hip and knee arthroplasty compared to placebo. The odds ratio indicates an approximately 30% decreased odds of developing POUR in the tamsulosin group, albeit not statistically significant. Tamsulosin does not appear to be effective as a prophylactic measure for reducing POUR in male hip and knee arthroplasty patients.

Objective To explore the intrinsic role of inhibitor of DNA binding 1 (ID‐1) in rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) and to investigate whether ID‐1 is citrullinated and autoantigenic in RA. Methods RA patient serum ID‐1 levels were measured before and after infliximab treatment. RA FLS were transfected with a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 construct targeting ID‐1 to examine the effects of ID‐1 deletion. RA synovial fluid (SF) and homogenized synovial tissue (ST) were immunoprecipitated for ID‐1 and measured for citrullinated residues using an enzyme‐linked immunosorbent assay and Western blotting. Liquid chromatography tandem mass spectrometry (LC‐MS/MS) was performed on in vitro–citrullinated recombinant human ID‐1 (cit–ID‐1) to localize the sites of citrullination. Normal and RA sera and SF were analyzed by immunodot blotting for anti–citrullinated protein antibodies (ACPAs) to cit–ID‐1. Results RA patient serum ID‐1 levels positively correlated with several disease parameters and were reduced after infliximab treatment. RA FLS displayed reduced growth and a robust increase in interleukin‐6 (IL‐6) and IL‐8 production upon deletion of ID‐1. ID‐1 immunodepletion significantly reduced the levels of citrullinated residues in RA SF, and citrullinated ID‐1 was detected in homogenized RA ST (n = 5 samples; P < 0.05). Immunodot blot analyses revealed ACPAs to cit–ID‐1 but not to native ID‐1, in RA peripheral blood (PB) sera (n = 30 samples; P < 0.001) and SF (n = 18 samples; P < 0.05) but not in normal PB sera. Following analyses of LC‐MS/MS results for citrullination sites and corresponding reactivity in immunodot assays, we determined the critical arginines in ID‐1 for autoantigenicity: R33, R52, and R121. Conclusion Novel roles of ID‐1 in RA include regulation of FLS proliferation and cytokine secretion as well as autoantigenicity following citrullination.

The present cross-sectional study of 230 teachers aimed to test Spilt, Koomen & Thijs's [Educational Psychology Review, 23, 457 (2011)] proposal that teachers' mental representations of their student relationships shape their affective responses to behaviour perceived as problematic. The association between student problematic behaviour and teachers' affective responses was mediated by relational conflict and this indirect effect was lessened by relational closeness. The degree to which teachers' attachment patterns were characterised by compulsive caregiving did not impact on these processes. The present study is consistent with relational theories of teacher wellbeing and argues for relationship-focused reflective practice in teacher training.

Linear Dichroism in Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy is a useful tool for studying molecular orientation and for clarifying spectroscopic assignments. n-Alkane molecules can form single crystals with different polymorphs; orthorhombic and monoclinic in the case of even chain lengths between n-C28H58 and n-C40H82. These polymorphs exhibit different linear dichroism in their NEXAFS spectra; in particular a backbone-oriented transition contributes to the low-energy “C–H” band in the monoclinic polymorph.

CD13, an ectoenzyme on myeloid and stromal cells, also circulates as a shed, soluble protein (sCD13) with powerful chemoattractant, angiogenic, and arthritogenic properties, which require engagement of a G protein-coupled receptor (GPCR). Here we identify the GPCR that mediates sCD13 arthritogenic actions as the bradykinin receptor B1 (B1R). Immunofluorescence and immunoblotting verified high expression of B1R in rheumatoid arthritis (RA) synovial tissue and fibroblast-like synoviocytes (FLSs), and demonstrated binding of sCD13 to B1R. Chemotaxis, and phosphorylation of Erk1/2, induced by sCD13, were inhibited by B1R antagonists. In ex vivo RA synovial tissue organ cultures, a B1R antagonist reduced secretion of inflammatory cytokines. Several mouse arthritis models, including serum transfer, antigen-induced, and local innate immune stimulation arthritis models, were attenuated in Cd13-/- and B1R-/- mice and were alleviated by B1R antagonism. These results establish a CD13/B1R axis in the pathogenesis of inflammatory arthritis and identify B1R as a compelling therapeutic target in RA and potentially other inflammatory diseases.

Severe acute respiratory syndrome coronavirus 2 is the virus that causes coronavirus disease 2019 (COVID-19). COVID-19 is a disease characterized by a range of clinical syndromes including variable degrees of respiratory symptoms from mild respiratory illness and severe interstitial pneumonia to acute respiratory distress syndrome, septic shock, coagulopathies, and multiorgan dysfunction. This virus carries the potential to manifest in a wide range of pulmonary findings and hypoxemias, from mild respiratory symptoms to more severe syndromes, such as acute respiratory distress syndrome. The rapid accumulation of evidence and persistent gaps in knowledge related to the virus presents a host of challenges for clinicians. This creates a complex environment for clinical decision-making.To examine oxygenation strategies in critically ill patients with hypoxia who are hospitalized with COVID-19.These proposed strategies may help to improve the respiratory status and oxygenation of those affected by COVID-19. However, additional high-quality research is needed to provide further evidence for improved respiratory management strategies. Areas of future research should focus on improving understanding of the inflammatory and clotting processes associated with the virus, particularly in the lungs. High-level evidence and randomized controlled trials should target the most effective strategies for improving oxygenation, time requiring mechanical ventilation, and survival for hospitalized patients with COVID-19 presenting with hypoxemia.

Postoperative pain management is particularly challenging in patients using opioids preoperatively, but previous studies have not stratified patients not using opioids at the time of surgery according to history of opioid use. This study was designed to test the hypothesis that history of opioid use among patients not reporting opioid use at the time of surgery was independently associated with new persistent opioid use after surgery.Using prospective perioperative data from the Analgesic Outcomes Study, we assessed outcomes of patients 18 years of age or older who underwent elective surgery between December 2015 and January 2019 and were not using opioids at the time of surgery. Patient self-reported outcome measures were collected on the day of surgery and at 2 weeks, 1 month, and 3 months postoperatively. The primary outcome was new persistent opioid use, defined as continued opioid use 3 months after surgery. The primary explanatory variable was history of opioid use, which was categorized as no history of opioid use, history of non-continuous opioid use, or history of continuous opioid use (defined as daily or almost every day for 3 months or longer). Other covariates included demographics, validated measures (pain, mood), surgery type and approach, comorbidities, and use of tobacco, alcohol, cannabis, and benzodiazepines. Backward stepwise logistic regression models were used to determine patient factors associated with new persistent opioid use and refill after surgery.A total of 1,249 patients not taking opioids preoperatively were included in the study cohort for new persistent opioid use. A total of 54 (4.3%) patients had continued use 3 months after surgery. New persistent opioid use after surgery was independently associated with non-continuous opioid use history (adjusted odds ratio 2.9, [95% confidence interval, 1.21 to 6.94]), continuous opioid use history (adjusted odds ratio 5.0, [95% confidence interval, 1.48 to 16.76]), and moderate to high alcohol use (adjusted odds ratio 2.5, [95% confidence interval, 1.24 to 4.93]). Similarly, opioid prescription refill at 1 month after surgery was independently associated with history of non-continuous opioid use (adjusted odds ratio 1.6, [95% confidence interval, 1.12 to 2.24]), history of continuous opioid use (adjusted odds ratio 2.2, [95% confidence interval, 1.15 to 4.06]), and moderate to high alcohol use (adjusted odds ratio 1.7, [95% confidence interval, 1.18 to 2.48]).Among patients not using opioids preoperatively, a history of opioid use was independently associated with new persistent opioid use after surgery, especially those with a history of continuous opioid use.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 is the virus that causes coronavirus disease 2019 (COVID-19). COVID-19 is a disease characterized by a range of clinical syndromes including variable degrees of respiratory symptoms from mild respiratory illness and severe interstitial pneumonia to acute respiratory distress syndrome, septic shock, coagulopathies, and multiorgan dysfunction. This virus carries the potential to manifest in a wide range of pulmonary findings and hypoxemias, from mild respiratory symptoms to more severe syndromes, such as acute respiratory distress syndrome. The rapid accumulation of evidence and persistent gaps in knowledge related to the virus presents a host of challenges for clinicians. This creates a complex environment for clinical decision-making. OBJECTIVE: To examine oxygenation strategies in critically ill patients with hypoxia who are hospitalized with COVID-19. DISCUSSION: These proposed strategies may help to improve the respiratory status and oxygenation of those affected by COVID-19. However, additional high-quality research is needed to provide further evidence for improved respiratory management strategies. Areas of future research should focus on improving understanding of the inflammatory and clotting processes associated with the virus, particularly in the lungs. High-level evidence and randomized controlled trials should target the most effective strategies for improving oxygenation, time requiring mechanical ventilation, and survival for hospitalized patients with COVID-19 presenting with hypoxemia.

The near edge X-ray absorption fine structure (NEXAFS) spectra of orthorhombic single crystals of n-octacosane (n-C28H58), recorded at room temperature (298 K) and at cryogenic temperatures (93 K),...

Background Depression and anxiety are common comorbidities in chronic pain including osteoarthritis patients undergoing total joint arthroplasty (TJA). What is not clear is whether psychiatric comorbidity precedes the manifestation of painful states or represents a reaction to living with chronic pain and associated functional impairment. The objective of this research was to explore whether decreases in depressive and anxiety symptoms after lower-extremity TJA could be due to postsurgical reductions in pain. Methods We conducted a secondary analysis of data from 1448 TJA patients enrolled in the Analgesics Outcome Study. Patients completed measures of pain intensity, functional status, and depressive and anxiety symptoms preoperatively and at 3 and 6 months postoperatively. Data were analyzed using a structural equation modeling approach. Results We found that improvement in pain and physical function from baseline to 6 months postoperatively was associated with improvement in depression and anxiety symptoms. We also found that a change in overall body pain at 3 months after surgery significantly mediated changes in both the depression and anxiety scores at 6 months after surgery even when controlling for age, sex, baseline body pain, education, opioid use, and type of surgery. Conclusions Presurgical affective symptoms not only have an effect on change in postsurgical pain, whereby lower preoperative scores on depression and anxiety were associated with lower postsurgical pain, but also postsurgical decreases in pain were associated with lower levels of depression and anxiety after surgery. Taking these points into consideration may prove useful in working toward better outcomes for TJA.

The origin of the exceptional stability of molecular glasses grown by physical vapor deposition (PVD) is not well understood. Differences in glass density have been correlated with thermodynamic stability for thin films of N,N'-Bis(3-methylphenyl)-N,N'-diphenylbenzidine (TPD) grown by PVD at specific substrate temperatures below the glass transition temperature. However, the relationship between the internal conformation of glass molecules and the thermodynamic properties of molecular glasses is not well studied. We use carbon 1s near edge x-ray absorption fine structure (NEXAFS) spectroscopy to examine different TPD sample preparations in which differences in the thermodynamic stability of the glass are known. Density functional theory simulations of the NEXAFS spectra of TPD allow us to attribute spectroscopic differences to changes in the internal conformation of the TPD molecule and relate this conformation to the stability of the TPD glass. This provides a direct experimental measurement of the internal conformation of molecules forming an organic glass.

Carbon 1s near edge X-ray absorption fine structure (NEXAFS) and UV–vis spectroscopy are used to examine differences between highly aggregated and poorly aggregated forms of the polymer poly(3-hexylthiophene) (P3HT), based on as-cast and annealed regiorandom and regioregular P3HT samples. UV–vis spectra show characteristic signatures of unaggregated P3HT in regiorandom P3HT, and of H-aggregation in regioregular P3HT samples. Distinct spectroscopic differences, including energy shifts, are observed in the NEXAFS spectra of aggregated P3HT relative to the unaggregated forms. These differences are reproduced with transition-potential density functional theory (TP-DFT) calculations which explore aggregation and molecular conformation. Differences in the NEXAFS spectra of P3HT are assigned to thiophene backbone twisting in the unaggregated forms of P3HT, and to various degrees of chain planarization in aggregated forms of P3HT that also correlate to the exciton bandwidth. These results open up the prospect of ...

NEXAFS spectroscopy has potential for study of packing and order in organic materials but only if intermolecular effects are understood. This work studies how π-π interactions between adjacent unsaturated groups affect their NEXAFS spectra, with a broader goal of building a general understanding of the role of intermolecular effects in NEXAFS spectroscopy. These effects are examined using paracyclophane (PCP) molecules, in which the benzene-benzene separation distance is controlled by varying the length of the alkyl groups separating the benzene rings. NEXAFS spectroscopy and density functional theory (DFT) simulations are used to examine spectroscopic changes related to the strength of these π-π interactions. A characteristic red shift is observed as adjacent benzene rings get closer together. This shift is attributed to Coulombic and orbital interactions between the adjacent benzene rings, mediated through overlapping π/π* orbitals.

Background The Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) has monitored discharge disposition, after total hip and knee arthroplasties, since inception in 2012 and found the standardized risk of extended care facility (ECF) placement to be highly variable between hospitals. Methods The variation in standardized risks of ECF placement among MARCQI member sites was reported to the collaborative. At the May 2, 2014 quarterly meeting, a quality initiative was started, emphasizing the wide variability between hospitals, the contribution of hospital and surgeon to that variability using median odds ratios, and the need for outlier hospitals to initiate quality improvement (QI) processes. Patients from 29 hospitals that were members of MARCQI before the intervention were included in this analysis. We compared standardized risks before and after the intervention in the entire cohort, and for 3 hospitals that implemented institution-specific QI projects. We report changes in ECF placement, length of stay, emergency room visits, and readmissions over time. Results This study includes 31,347 patients before and 20,879 patients after the implementation of the quality initiative. The range in standardized risk dropped from 9.4%-46.1% to 9.4%-32.4% and the average dropped from 23.0% to 19.6%. Three outlier hospitals decreased their absolute risk of ECF placement by 12.2%, 8.9%, and 12.4% after QI, without increases in adverse outcomes. Conclusion Discharge to ECF after primary hip and knee arthroplasties is highly variable and influenced by hospital and surgeon practices. Hospital-level QI measures can decrease ECF admissions.

Accurate sagittal alignment of the femoral component in total knee arthroplasty is crucial for prosthesis longevity, improved function, and patient satisfaction. However, there is variation in the techniques used to attain optimal sagittal femoral component placement in total knee arthroplasty. Femoral component flexion in imageless navigation is based on the mechanical axis rather than the distal femoral anatomy, and there is significant variability in the anatomy of the distal femur. The purpose of this study was to accurately determine the mean distal femoral flexion angle of a representative population and whether variability of the distal femoral flexion angle correlates with race, femur length, or radius of curvature. The mean degree of distal femoral flexion was determined by assessing distal femoral anatomy on computed tomography scans of paired femurs of 1235 patients without evidence of previous fracture, deformity, or surgical implants. The mean±SD distal femoral flexion angle was 2.90°±1.52°, with 80.2% of knees within 3°±2°. Therefore, placing the component in 3° of flexion from the mechanical axis would attain a satisfactory position in most cases. However, further analysis of the patient data revealed 11.4% of Asians, 7.3% of African Americans, and 8.3% of whites had a distal femoral flexion angle greater than 5°. Additionally, the data revealed a moderately strong negative correlation between the distal femoral flexion and the overall radius of curvature of the femur. This preliminary study highlights the need for improved methods for selecting femoral component position in the sagittal plane when using navigation for total knee arthroplasty. [ Orthopedics. 2017; 40(2):102–106.]

Aminopeptidase N/CD13 is expressed by fibroblast-like synoviocytes (FLS) and monocytes (MNs) in inflamed human synovial tissue (ST). This study examined the role of soluble CD13 (sCD13) in angiogenesis, MN migration, phosphorylation of signaling molecules, and induction of arthritis. The contribution of sCD13 was examined in angiogenesis and MN migration using sCD13 and CD13-depleted rheumatoid arthritis (RA) synovial fluids (SFs). An enzymatically inactive mutant CD13 and intact wild-type (WT) CD13 were used to determine whether its enzymatic activity contributes to the arthritis-related functions. CD13-induced phosphorylation of signaling molecules was determined by Western blotting. The effect of sCD13 on cytokine secretion from RA ST and RA FLS was evaluated. sCD13 was injected into C57BL/6 mouse knees to assess its arthritogenicity. sCD13 induced angiogenesis and was a potent chemoattractant for MNs and U937 cells. Inhibitors of Erk1/2, Src, NF-κB, Jnk, and pertussis toxin, a G protein–coupled receptor inhibitor, decreased sCD13-stimulated chemotaxis. CD13-depleted RA SF induced significantly less MN migration than sham-depleted SF, and addition of mutant or WT CD13 to CD13-depleted RA SF equally restored MN migration. sCD13 and recombinant WT or mutant CD13 had similar effects on signaling molecule phosphorylation, indicating that the enzymatic activity of CD13 had no role in these functions. CD13 increased the expression of proinflammatory cytokines by RA FLS, and a CD13 neutralizing Ab inhibited cytokine secretion from RA ST organ culture. Mouse knee joints injected with CD13 exhibited increased circumference and proinflammatory mediator expression. These data support the concept that sCD13 plays a pivotal role in RA and acute inflammatory arthritis.

We report the first detection of a glitch in the radio pulsar PSR J0908$-$4913 (PSR B0906$-$49) during regular timing observations by the Molonglo Observatory Synthesis Telescope (MOST) as part of the UTMOST project., Comment: 2 pages, 1 table

In a series of solid organ transplant (SOT) recipients who underwent a subsequent primary total joint arthroplasty (TJA) procedure, this study aimed to determine: (1) 90-day morbidity and mortality after primary total knee or hip arthroplasty (TKA and THA), (2) overall post-operative infection rates, and (3) how complication and infection rates compared across primary TJA procedure and type of transplant organ. The University of Michigan Health System database was retrospectively searched using current procedural terminology codes for any primary TKA or THA performed at the institution in years 2000–2012 in a patient who previously received a successful SOT at any hospital. The search yielded 44 arthroplasties performed in 29 SOT recipients (average age 54.8 years, average follow-up about 30 months for both groups). No deaths were reported, but 13/27 (48.1%) THA patients and 2/6 (33.3%) TKA patients experienced a total of 29 complications within 90 days of surgery. One patient (3.7%) [1/27 patients, 1/37 joints] underwent revision hip arthroplasty to correct limb length. One THA patient and two TKA patients developed infection requiring revision surgery (3.7% and 33%, respectively). Type of transplant did not affect complication rates (P=0.65), and infection was more common after TKA (P=0.01). A series of SOT recipients demonstrated increased rates of infection and other complications following TJA. Surgical and medical teams should work closely to optimize this population for TJA surgery and minimize peri-operative complications. Level IV, Prognostic Case-Series.

The carbon 1s near edge X-ray absorption fine structure (NEXAFS) spectra of liquid phase n-alkanes have been measured for the first time. Clear trends are observed in the liquid phase spectra as a function of chain length. Specifically, the ‘C-H band’ in the NEXAFS spectra shifts to lower energy as the chain length increases. Characteristic differences between the gas, liquid and solid phase spectra are observed. Differences in the liquid phase n-alkane NEXAFS spectra are examined through molecular dynamics simulations coupled with density functional theory simulations of the NEXAFS spectra.

A cryo scanning transmission X-ray microscope, the cryo-STXM, has been designed and commissioned at the Canadian Light Source synchrotron. The instrument is designed to operate from 100 - 4000 eV (lambda = 12.4 - 0.31 nm). Users can insert a previously frozen sample, through a load lock, and rotate it plus minus 70 degrees in the beam to collect tomographic data sets. The sample can be maintained for extended periods at 92 K primarily to suppress radiation damage, and a pressure on the order of 10-9 Torr to suppress sample contamination. The achieved spatial resolution (30 nm) and spectral resolution (0.1 eV) are similar to other current soft X-ray STXMs, as demonstrated by measurements on known samples and test patterns. The data acquisition efficiency is significantly more favorable for both imaging and tomography. 2D images, 3D tomograms and 4D chemical maps of automotive hydrogen fuel cell thin sections are presented to demonstrate current performance and new capabilities, namely cryo-spectrotomography in the soft X-ray region., 56 pages

We report the detection of a glitch event in the pulsar J1709$-$4429 (also known as B1706$-$44) during regular monitoring observations with the Molonglo Observatory Synthesis Telescope (UTMOST). The glitch was found during timing operations, in which we regularly observe over 400 pulsars with up to daily cadence, while commensally searching for Rotating Radio Transients, pulsars, and FRBs. With a fractional size of $\Delta\nu/\nu \approx 52.4 \times10^{-9}$, the glitch reported here is by far the smallest known for this pulsar, attesting to the efficacy of glitch searches with high cadence using UTMOST., Comment: 3 pages, 1 figure

OBJECTIVES: The present study evaluated the relationship between the 2011 American College of Rheumatology fibromyalgia (FM) survey criteria and quantitative sensory testing (QST). METHODS: Patients with knee osteoarthritis scheduled to undergo knee arthroplasty completed the FM survey criteria and self-report measures assessing clinical symptoms. Patients also underwent a battery of QST procedures at the surgical knee and remote body sites, including pressure algometry, conditioned pain modulation (CPM), and temporal summation (TS). All assessments were completed prior to surgery. FM survey criteria were used to calculate a continuous FM score indicating FM severity. RESULTS: 129 patients were analyzed. Of these, 52.7% were female, 93.8% were Caucasian, and 3.8% met the FM survey criteria for FM classification. Mean age for females (63.57 years) and males (64.74 years) was similar. Females and males differed significantly in nearly every outcome, including FM severity, clinical pain, anxiety, depression, and pressure pain sensitivity. In females, FM scores significantly correlated with pressure pain sensitivity, but not CPM or TS, such that increased sensitivity was associated with greater FM severity at all body sites examined. Additionally, as FM scores increased, the association between pain sensitivity at the surgical knee and that at remote body sites also increased. No relationship between FM score and QST was observed in males. DISCUSSION: We demonstrated an association between diffuse hyperalgesia as measured by QST and FM severity in females with knee osteoarthritis. These results suggest that the FM survey criteria may represent a marker of pain centralization in females with potential utility in clinical decision making.

Background Empirical evidence suggests that the Solihull Approach parenting group, ‘Understanding Your Child's Behaviour’ (UYCB), can improve child behaviour and parental well-being. However, little is known about parents' in-depth experience of participating in the UYCB programme. This study provides an in-depth qualitative evaluation of UYCB, focussing on possible moderating factors and mechanisms of change that may inform programme development. Method Ten parents (eight mothers and two fathers), recruited from seven UYCB groups across two locations, were interviewed within 7 weeks of completing the group and again 10 months later. Data were analysed using interpretative phenomenological analysis. Results Four themes were identified: ‘Two Tiers of Satisfaction’, ‘Development as a Parent’, ‘Improved Self-belief’ and ‘The “Matthew Effect”’. In summary, the majority of parents were immensely satisfied at both completion and follow-up: they valued an experience of containment and social support and perceived improvement in specific child difficulties, their experience of parenting, their confidence and their coping. Most parents appeared to have developed more reflective and empathic parenting styles, with self-reported improved behaviour management. Theoretical material was well received, although some struggled with technical language. Positive outcomes appeared to be maintained, even reinforced, at follow-up, and were associated with having few initial child difficulties, perceiving improvement at completion and persevering with the recommendations. Two participants, whose children had the most severe difficulties, perceived deterioration and felt that the group was insufficient for their level of difficulties. Conclusion Through in-depth analysis of parental experiences, UYCB appears to achieve its aims and communicate well its theoretical principles, although change may also occur through processes common to other group programmes (e.g. social support). Recommendations, stemming from the experiences of these parents, include simplified language, separate groups for parents with complex needs, greater emphasis on the importance of perseverance, and additional support for parents who appear to be struggling to make changes.

The purpose of this study was to determine the reliability of 1 repetition maximum (1RM) split squat (SS) and establish the efficacy of collecting 1RM-SS and 1RM bilateral squat (BLS) data in the same session, for a non-resistance-trained recreationally active population. Fourteen males performed a submaximal familiarization session and 5 testing sessions. After familiarization, the 1RM-SS was tested in the following 3 sessions. In session 4, subjects were tested in both 1RM-SS and 1RM-BLS, with half performing SS then BLS and the remainder BLS then SS. In session 5, the testing order was reversed. Reliability statistics calculated included the following: changes in mean across sessions, coefficient of variation calculated from the typical error (TE) scores (%CV(TE)), and test-retest reliability (intraclass correlation coefficient [ICC]) of 1RM-SS. Statistically significant differences between the mean 1RM-SS in sessions 1 and 2 (2.14 kg, p = 0.001), and sessions 1 and 3 (2.86 kg, p < 0.003) were found, indicating the requirement for an additional familiarization session before 1RM-SS data collection. The %CV(TE) was 2.53% and the ICC was 0.97 for the 1RM-SS protocol. Performing SS before BLS tended to increase the mean 1RM-BLS (+2.1%), although the difference was not significant (p = 0.055). A reliable measure of 1RM-SS can be determined after 1 submaximal and 1 maximal familiarization session in non-resistance-trained recreationally active men. Analysis of the current data suggests that it is appropriate to perform both 1RM-SS and 1RM-BLS tests within the same testing session if 1RM-SS is performed before 1RM-BLS. However, further testing is warranted to firmly establish the effects of 1RM-SS on subsequent 1RM-BLS.

Objective While psychosocial factors have been associated with poorer outcomes after knee and hip arthroplasty, we hypothesized that augmented pain perception, as occurs in conditions such as fibromyalgia, may account for decreased responsiveness to primary knee and hip arthroplasty. Methods A prospective, observational cohort study was conducted. Preoperative phenotyping was conducted using validated questionnaires to assess pain, function, depression, anxiety, and catastrophizing. Participants also completed the 2011 fibromyalgia survey questionnaire, which addresses the widespread body pain and comorbid symptoms associated with characteristics of fibromyalgia. Results Of the 665 participants, 464 were retained 6 months after surgery. Since individuals who met criteria for being classified as having fibromyalgia were expected to respond less favorably, all primary analyses excluded these individuals (6% of the cohort). In the multivariate linear regression model predicting change in knee/hip pain (primary outcome), a higher fibromyalgia survey score was independently predictive of less improvement in pain (estimate −0.25, SE 0.044; P

A new scanning transmission X-ray microscope (STXM) optimized for cryo-spectro-tomography with soft X-rays has been designed, built and commissioned at Canadian Light Source (CLS) beamline 10ID1 (130-2700 eV). It is controlled via a new python-based software package, pySTXM. A liquid N2 goniometer (Gatan 630, -80° to 80°), mounted on a computer controlled (x,y,Theta) tilt stage allows for spectro-tomographic measurements at cryogenic temperatures (-180°C) which reduces radiation damage. The CLS cryo-STXM is unique among the set of soft X-ray STXMs currently installed around the world. Details of the cryo-STXM design and examples of its performance will be presented.

Objective Aminopeptidase N/CD13 (EC 3.4.11.2) is a metalloproteinase expressed by fibroblast-like synoviocytes (FLS). It has been suggested that CD13 can act chemotactically for T cells in rheumatoid arthritis (RA). We undertook this study to measure CD13 in vivo and in vitro in RA samples and to determine whether CD13 could play a role in the homing of T cells to the RA joint. Methods Interleukin-17–treated FLS were used to immunize mice, from which a novel anti-human CD13 monoclonal antibody (mAb), 591.1D7.34, was developed. The mAb 591.1D7.34 and a second anti-CD13 mAb, WM15, were used to develop a novel enzyme-linked immunosorbent assay (ELISA) for CD13, and CD13 enzymatic activity was measured in parallel. Chemotaxis of cytokine-activated T cells was measured by a chemotaxis-under-agarose assay. Results We detected substantial amounts of CD13 in synovial fluid (SF), sera, FLS lysates, and culture supernatants by ELISA, with a significant increase in CD13 in RA SF when compared to osteoarthritis SF. CD13 accounted for most but not all of the CD13-like enzymatic activity in SF. Recombinant human CD13 was chemotactic for cytokine-activated T cells through a G protein–coupled receptor and contributed to the chemotactic properties of SF independently of enzymatic activity. Conclusion CD13 is released from FLS into culture supernatants and is found in SF. CD13 induces chemotaxis of cytokine-activated T cells, a T cell population similar to that found in RA synovium. These data suggest that CD13 could play an important role as a T cell chemoattractant, in a positive feedback loop that contributes to RA synovitis.

Sulfur 1s NEXAFS spectroscopy is sensitive to sulfur speciation; however, the overlapping energy position of the white line in the spectra of thiols and disulfides can be problematic for speciation. We have acquired highly resolved sulfur 1s NEXAFS spectra of a group of disulfides with aliphatic and unsaturated ligand groups. Spectral transitions were assigned by the aid of Improved Virtual Orbital (IVO) ab initio calculations. These results confirm how molecular symmetry and the ligand group can affect the NEXAFS spectra, and show how the NEXAFS spectra of thiols and disulfides can be used for chemical speciation.

High-resolution sulfur 1s NEXAFS spectra of a series of sulfoxides and sulfones have been obtained, and are assigned with the aid of ab initio improved virtual orbital (IVO) calculations. Spectral differences between sulfones and sulfoxides are attributed to the sulfur oxidation state and the energy spacing between unoccupied molecular orbitals. The character of the white line in sulfones depends on the sulfur ligand groups, where an aromatic ligand causes a red shift and a broadening of the white line. These effects can pose challenges for speciation when the white line of sulfones overlaps with that of sulfoxide.

Sulfur plays an important role in the rubber industry as a vulcanizing agent, providing an enhancement in mechanical properties relative to unvulcanized rubber. The sulfur used in industry originates from natural and petroleum sources. Petroleum-based sulfur (PS), usually a by-product from a refinery process, was used as the vulcanizing sulfur in the present work. The chemical structure of PS was characterized and compared to that of a commercial rhombic sulfur (RS) using sulfur K-edge X-ray absorption near-edge structure (XANES) spectroscopy. The results reveal that sulfur K-edge XANES spectroscopy has good sensitivity to the chemical structure of sulfur, and the chemical structures of sulfur in rubbers vulcanized with PS and RS are very similar. Furthermore, different types of rubbers vulcanized with PS or RS exhibit comparable mechanical properties. This work shows that PS can be used to replace RS as a vulcanizing agent for rubber.

Objective To examine the association of adolescent and parent diabetes distress with perceived consequences, dietary self-efficacy, and discrepancies in diabetes family responsibility, in type 1 diabetes (T1D). Methods 203 adolescents with T1D, aged 12–18, and their parents completed self-report questionnaires cross-sectionally. Results Higher HbA1c, greater perceived negative consequences of diabetes, and reduced self-efficacy predicted adolescent diabetes distress. Higher HbA1c predicted parental diabetes distress, as did diabetes family responsibility disagreements when both family members claimed responsibility, and parents' perception of reduced adolescent self-efficacy. Conclusion Dietary self-efficacy and perceived negative consequences of diabetes are important factors to consider in assessing and managing adolescent diabetes distress. Perceptions of family responsibility for self-care tasks and parental confidence in adolescents' self-management have implications for parental diabetes distress. Clinical implications support long-held recommendations of taking a family-perspective of T1D care.

We have quantitatively measured the angle dependence in the Silicon 1s X-ray absorption spectra of strained Si1−xGex thin films prepared by epitaxial growth on Si(1 0 0) substrates, through surface sensitive total electron yield detection. The linear dichroism difference extracted from these angle dependent X-ray absorption spectra is proportional to the degree of strain, as measured separately by Raman spectroscopy. This quantitative relationship provides a means to measure the compressive strain in Si1−xGex thin films. This strain-dependent X-ray absorption spectroscopy has the potential to realize a semiconductor strain metrology through high spatial resolution X-ray spectromicroscopy.