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Implant migration is a predictor of arthroplasty survivorship. It is crucial to monitor the migration of novel hip prostheses within premarket clinical investigations. RSA is the gold standard method, but requires calibrated radiographs using specialised equipment. A commercial computed tomography micromotion analysis solution is a promising alternative but is not yet available for use with monobloc ceramic implants. This study aimed to develop and validate a CT-based spatial analysis (CTSA) method for use with ceramic implants. A phantom study was undertaken to assess accuracy and precision. A ceramic hip resurfacing arthroplasty (HRA) and 20 tantalum beads were implanted into a synthetic hip model and mounted onto a 6-degree of freedom motion stage. The hip was repeatedly scanned with a low dose CT protocol, with imposed micromovements. Data were interrogated using a semiautomated technique. The effective radiation dose for each scan was estimated to be 0.25 mSv. For the head implant, precision ranged between 0.11 and 0.28 mm for translations and 0.34°–0.42° for rotations. For the cup implant, precision ranged between 0.08 and 0.11 mm and 0.19° and 0.42°. For the head, accuracy ranged between 0.04 and 0.18 mm for translations and 0.28°–0.46° for rotations. For the cup, accuracy ranged between 0.04 and 0.08 mm and 0.17° and 0.43°. This in vitro study demonstrates that low dose CTSA of a ceramic HRA is similar in accuracy to RSA. CT is ubiquitous, and this method may be an alternative to RSA to measure prosthesis migration.

This paper presents the results of the electrical conductivity measurements of sand–clay mixtures that were formed of three types of sands and five pure clays and prepared with water of low salinity. The results show that an increase in clay content results in an increase in the overall electrical conductivity. Moreover, a direct or inverse relationship between the overall soil electrical conductivity (σ T) and porosity (n) is observed depending on whether the water conductivity (σw) is higher or lower than the clay particle surface conductivity (σ s). Common predictive models for electrical conductivity were developed for sands and clayey sands with a clay content of less than 20%. This research extended these studies to include clays, sandy clays and clayey sands to show that it is possible to predict the electrical conductivity of a soil from its composition and fabric.

Most adults return to smoking after enforced tobacco abstinence when incarcerated in US prisons. Little is known about the specific relapse triggers on reentry. This study examines situational, affective, and motivational antecedents of return to smoking immediately after release from a tobacco-free prison.Assessments were administered before release and 1 and 7 days after release to 190 incarcerated adults who were smokers before incarceration. Those reporting smoking within 7 days after release were asked about circumstances surrounding their first cigarette.Two-thirds reported smoking in the 7 days after release (76% of those in the first day) with the first cigarette smoked 21 hours after release on average. Smoking occurred more quickly for women than men and for those who planned to smoke after release ( P values from 0.05 to 0.001). Forty-one percent of participants smoked while waiting for a ride or on the way home, 68% were given their first cigarette, 28% reported first smoking when reuniting with others, 42% first smoked with smokers, and 26% first smoked as celebration. The moods most reported before smoking were happy (60%) or excited (41.5%). Factors reported that could have prevented smoking were avoiding other smokers (27%), avoiding stress (16%), not drinking/using drugs (12%), and not having access to cigarettes (11%).High rates of return to smoking occurred rapidly when around other smokers, using other substances, and in a positive mood. Interventions that focus specifically on these factors and can be immediately accessed upon release are required to help sustain people's desired abstinence.

Background Ovarian cancer patients frequently develop chemotherapy resistance, limiting treatment options. We have previously shown that individuality in fibroblast growth factor 1 (FGF1) expression influences survival and chemotherapy response. Methods We used MTT assays to assess chemosensitivity to cisplatin and carboplatin following shRNA-mediated knockdown or heterologous over-expression of FGF1 (quantified by qRT-PCR and immunoblot analysis), and in combination with the FGFR inhibitors AZD4547 and SU5402, the ATM inhibitor KU55933 and DNA-PK inhibitor NU7026. Immunofluorescence microscopy was used to quantify the FGF1-dependent timecourse of replication protein A (RPA) and γH2AX foci formation. Results Pharmacological inhibition of FGF signalling reversed drug resistance in immortalised cell lines and in primary cell lines from drug-resistant ovarian cancer patients, while FGF1 over-expression induced resistance. Ataxia telangiectasia mutated (ATM) phosphorylation, but not DNA adduct formation was FGF1 dependent, following cisplatin or carboplatin challenge. Combining platinum drugs with the ATM inhibitor KU55933, but not with the DNA-PK inhibitor NU7026 re-sensitised resistant cells. FGF1 expression influenced the timecourse of damage-induced RPA and γH2AX nuclear foci formation. Conclusion Drug resistance arises from FGF1-mediated differential activation of high-fidelity homologous recombination DNA damage repair. FGFR and ATM inhibitors reverse platinum drug resistance, highlighting novel combination chemotherapy approaches for future clinical trial evaluation.

Results from this large, multicenter study suggest that patients with a confirmed ciprofloxacin, moxifloxacin, or levofloxacin hypersensitivity reaction are likely to tolerate other fluoroquinolones. Avoiding different fluoroquinolones in patients labeled with a ciprofloxacin, moxifloxacin, or levofloxacin allergy may not always be mandatory.

Inflammation and oxidative stress in pancreatic islets amplify the appearance of various posttranslational modifications to self-proteins. In this study, we identified a select group of carbonylated islet proteins arising before the onset of hyperglycemia in NOD mice. Of interest, we identified carbonyl modification of the prolyl-4-hydroxylase β subunit (P4Hb) that is responsible for proinsulin folding and trafficking as an autoantigen in both human and murine type 1 diabetes. We found that carbonylated P4Hb is amplified in stressed islets coincident with decreased glucose-stimulated insulin secretion and altered proinsulin-to-insulin ratios. Autoantibodies against P4Hb were detected in prediabetic NOD mice and in early human type 1 diabetes prior to the onset of anti-insulin autoimmunity. Moreover, we identify autoreactive CD4+ T-cell responses toward carbonyl-P4Hb epitopes in the circulation of patients with type 1 diabetes. Our studies provide mechanistic insight into the pathways of proinsulin metabolism and in creating autoantigenic forms of insulin in type 1 diabetes.

OBJECTIVE To determine whether silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) or laparoscopic sleeve gastrectomy (LSG) produces superior diabetes remission at 5 years. RESEARCH DESIGN AND METHODS In a single-center, double-blind trial, 114 adults with type 2 diabetes and BMI 35–65 kg/m2 were randomly assigned to SR-LRYGB or LSG (1:1; stratified by age-group, BMI group, ethnicity, diabetes duration, and insulin therapy) using a web-based service. Diabetes and other metabolic medications were adjusted according to a prespecified protocol. The primary outcome was diabetes remission assessed at 5 years, defined by HbA1c RESULTS Diabetes remission after SR-LRYGB versus LSG occurred in 25 (47%) of 53 vs. 18 (33%) of 55 patients (adjusted odds ratios 4.5 [95% CI 1.6, 15.5; P = 0.009] and 4.2 [1.3, 13.4; P = 0.015] in the intention-to-treat analysis). Percent body weight loss was greater after SR-LRYGB than after LSG (absolute difference 10.7%; 95% CI 7.3, 14.0; P < 0.001). Improvements in cardiometabolic risk factors were similar, but HDL cholesterol increased more after SR-LRYGB. Early and late complications were similar in both groups. General health and physical functioning improved after both types of surgery, with greater improvement in physical functioning after SR-LRYGB. People of Māori or Pacific ethnicity (26%) had lower incidence of diabetes remission than those of New Zealand European or other ethnicities (2 of 25 vs. 41 of 83; P < 0.001). CONCLUSIONS SR-LRYGB provided superior diabetes remission and weight loss compared with LSG at 5 years, with similar low risks of complications.

The spontaneous L-isoaspartate protein modification has been observed to negatively affect protein function. However, this modification can be reversed in many proteins in reactions initiated by the protein-L-isoaspartyl (D-aspartyl) O-methyltransferase (PCMT1). It has been hypothesized that an additional mechanism exists in which L-isoaspartate-damaged proteins are recognized and proteolytically degraded. Herein, we describe the protein-L-isoaspartate O-methyltransferase domain-containing protein 1 (PCMTD1) as a putative E3 ubiquitin ligase substrate adaptor protein. The N-terminal domain of PCMTD1 contains L-isoaspartate and AdoMet binding motifs similar to those in PCMT1. This protein also has a C-terminal domain containing SOCS-box ubiquitin ligase recruitment motifs found in substrate receptor proteins of the Cullin-RING E3 ubiquitin ligases. We demonstrate specific PCMTD1 binding to the canonical methyltransferase cofactor S-adenosylmethionine (AdoMet). Strikingly, while PCMTD1 is able to bind AdoMet, it does not demonstrate any L-isoaspartyl methyltransferase activity under the conditions tested here. However, this protein is able to associate with the Cullin-RING proteins Elongins B and C and Cul5 in vitro and in human cells. The previously uncharacterized PCMTD1 protein may therefore provide an alternate maintenance pathway for modified proteins in mammalian cells by acting as an E3 ubiquitin ligase adaptor protein.

BackgroundThe objectives of this study were to describe the changing epidemiology of gram-negative infective endocarditis (GNIE) and to identify factors associated with treatment failure and death.MethodsAdult patients with GNIE were included if they met modified Duke criteria for definitive infective endocarditis (IE) between April 2010 and December 2021. Patients were identified using Boolean search terms. Clinical failure was a defined as a composite of all-cause 42-day mortality or microbiologic failure. All analyses were performed using Stata, version 15.1.ResultsOne-hundred twenty-three patients were included. The most common pathogens were Serratia spp. (43%), Pseudomonas aeruginosa (21%), and Klebsiella spp. (14%). Fifty-two percent of cases were among persons who injection drugs (PWID; n = 64), for whom Serratia spp. (70%) was the most common cause of GNIE. Overall, patients infected with P. aeruginosa had higher microbiologic failure rates than other patients (23% vs 6%; P = .004). Patients who received combination therapy (n = 53) had comparable median lengths of stay (23 vs 19.5 days; P = .412), microbiologic failure rates (11.3% vs 7.1%; P = .528), clinical failure rates (18.9% vs 22.9%; P = .592), and 90-day mortality rates (13.2% vs 25.7%; P = .088) as those treated with monotherapy. After applying stepwise logistic regression, male gender, Pitt Bacteremia Score, and not receiving surgical intervention despite a surgical indication were associated with clinical failure.ConclusionsThis is the first study to identify Serratia spp. as the most common etiology of GNIE, which was particularly true among PWID. Microbiologic failures occurred most commonly among P. aeruginosa, and use of combination antimicrobial therapy did not improve clinical outcomes.

BACKGROUND Despite male youth taking more sexual risks that lead to unwanted partner pregnancy and/or sexually transmitted infections (STIs), research evaluating interventions for risky sex has focused almost exclusively on adolescent and adult females. With STIs among male youth on the rise, behavioral interventions that target risky sex among male youth are needed. PURPOSE A randomized controlled pilot study was conducted to examine the feasibility and acceptability of two manualized behavioral interventions for sexually active male youth. METHODS Sexually active at-risk male youth (N = 27) were recruited and randomized to receive one session of motivational interviewing (MI) or didactic educational counseling (DEC). Assessment interviews were conducted prior to and 3 months following the intervention session. RESULTS Support for the feasibility and acceptability of delivering behavioral interventions to reduce risky sexual behaviors among at-risk male youth was found. Compared to participants in DEC at follow-up, participants in MI reported having significantly fewer sexual encounters with casual partners, used substances at the time of sex significantly less often with all partners and casual partners, and reported fewer incidents of using substances at the time of sex without a condom with all partners. Conversely, participants who received MI used substances at the time of sex with main partners and used substances at the time of sex without a condom more often with main partners at follow-up compared to participants who received DEC. CONCLUSIONS Results of the pilot study support conducting a larger randomized controlled trial to examine treatment effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cellular metabolism generates molecular damage affecting all levels of biological organization. Accumulation of this damage over time is thought to play a central role in the aging process, but damage manifests in diverse molecular forms complicating its assessment. Insufficient attention has been paid to date to the role of molecular damage in aging-related phenotypes, particularly in humans, in part because of the difficulty in measuring its various forms. Recently, omics approaches have been developed that begin to address this challenge, because they are able to assess a sizeable proportion of age-related damage at the level of small molecules, proteins, RNA, DNA, organelles and cells. This review describes the concept of molecular damage in aging and discusses its diverse aspects from theoretical models to experimental approaches. Measurement of multiple types of damage enables studies of the role of damage in human aging outcomes and lays a foundation for testing interventions to reduce the burden of molecular damage, opening new approaches to slowing aging and reducing its consequences.

How does an entrepreneur’s social capital improve small informal business productivity? Although studies have investigated this relationship, we still know little about the underlying theoretical mechanisms driving these findings. Using a unique Zambian Business Survey of 1971 entrepreneurs administered by the World Bank, we find an entrepreneur’s social capital facilitates small business productivity through the mediating channels of firm financing (i.e., credit from suppliers, credit to customers, loans from friends and family) and customer relationships (i.e., more customers). Our findings, thus, identify specific mechanisms that channel social capital toward an informal business’ productivity, which prior studies have overlooked. Small informal businesses are more productive when they build relationships with customers, extend credit to customers, and receive credit from suppliers and friends and family. Using a unique survey of 1,971 Zambian entrepreneurs administered by the World Bank, we observe that belonging to a business or social association enables these businesses to extend credit, receive credit, and build relationships. Our findings provide more specific mechanisms that channel social capital toward an informal business’ productivity, which prior studies have overlooked. Thus, our main policy recommendation is that entrepreneurs, especially from informal businesses and developing contexts, should focus on networking to foster customer and professional relationships and enhance access to capital, which can help foster firm productivity.

Helically chiral boron-chelated dipyrromethene (BODIPY) dyes are known to exhibit solution phase circularly polarized luminescence (CPL), but examples are limited to a few synthetically accessible molecular architectures. We report a B−N chelation, SNAr, Suzuki cross-coupling, B−O chelation cascade reaction for the synthesis of understudied helically chiral, N,N,O,C-boron chelated, “confused” BODIPYs, from readily accessible 3,5-dibromo-BODIPY starting materials. Using this approach we have prepared a series of helically chiral “confused” BODIPYs with variation of the 3,5-subsitutents. Following resolution by chiral HPLC, absolute stereochemistry was assigned through comparison of the experimental and calculated ECD spectra, and solution phase chiroptical properties including CPL were determined (|glum| from 2.1 to 3.7×10−3; BCPL from 11.3 to 27.2).

This article performs the becoming intimacy of a reading (and, later, writing) group who met once a month for 2 years to discuss Deleuze and Guattari’s A Thousand Plateaus. Through this collaborative piece, we explore the question of intimacy as both a form of activism and a mode of inquiry. We ask, “Where is activism as we subvert the hierarchy of academia by meeting as an assemblage of differing perspectives and positions in the university?” Furthermore, we ask, “What does the intimacy that occurred, that is occurring, do for both inquiry and activism?.” This article contains two sets of writing from our monthly meetings that we offered as performative conference texts. We contend that it is affect that brings our theorizing to life, and transfers it meaningfully between each other. We are affected by Deleuze and Guattari, by A Thousand Plateaus, and by how we form linkages with our lives to these bodies. Intimacy is what sustains and gives life to our collective inquiry, without which our affect might be more constrained. The complexity of the becoming of “intimacy as inquiry” becomes twofold, as it is not only a becoming of intimacy, love, and care for those in our assemblage but also a reterritorialization of the act of inquiry. Through the act of disrupting power structures in the group of “We 5,” the act of writing and presenting this work in an academic context pushes against the striated spaces that exist in the academy, that course through the milieu we occupy, and provides the means and necessity for reterritorializing the epistemic space. “Epistemic intimacy,” then, becomes a manifestation of engaging with the inquiry process and embodies an active resistance to the business transaction that the act of inquiry has become in the neoliberal development of the academy.

To decrease opioid overdose mortality, prisons and jails in the US are increasingly offering medications for opioid use disorder (OUD) to incarcerated people. It is unknown how receipt of these medications in a correctional setting affects health services use after release. In this article we analyze changes in postrelease health care use after the implementation of a statewide medications for OUD program in the unified jail and prison system of the Rhode Island Department of Corrections. Using Medicaid claims data, we examined individual health care use in the community before and after receipt of medications for OUD while incarcerated. We found that inpatient admissions did not change, emergency department visits decreased, and both nonacute outpatient services and pharmacy claims increased after people received medications for OUD while incarcerated. There was no change in total health care costs paid by Medicaid. Our findings provide evidence that people's use of health care services paid for by Medicaid did not increase after they started medications for OUD in correctional settings. Given the frequent interaction of people with OUD with the criminal justice system, offering evidence-based treatment of OUD in correctional settings is an important opportunity to initiate addiction treatment.