Metal Ion Levels in Young, Active Patients Receiving a Modular, Dual Mobility Total Hip Arthroplasty.

BACKGROUND: Dual mobility total hip arthroplasty (THA) components improve stability, yet use of a modular cobalt alloy acetabular liner may be associated with metal ion release. This study's purpose was to measure blood metal ion levels in young, active patients receiving a dual mobility THA prosthesis. METHODS: This is a prospective study of young, active patients undergoing primary THA. Twenty-six patients received a 22-mm cobalt alloy (n = 10) or a 28-mm ceramic (n = 16) femoral head, a modular cobalt chrome acetabular liner, with a highly cross-linked polyethylene insert (dual mobility). Seventeen control patients received a 32-mm cobalt alloy (n = 6), oxidized zirconium (n = 5), or ceramic (n = 6) femoral head and polyethylene acetabular liner (conventional). All patients received a cementless, titanium femoral stem. Blood metal ion levels (µg/L) were measured preoperatively and at 1 year postoperatively. RESULTS: No difference was present for age or body mass index (P = .5 and .9). At 1 year postoperatively, mean cobalt levels were greater in the dual mobility cohort (0.23 ± 0.39 vs 0.15 ± 0.07, P < .001). Four patients in the dual mobility cohort had a cobalt level outside the reference range (0.03-0.29), with values from 0.34 to 1.81 µg/L. One patient in the conventional cohort had a cobalt level outside the reference range with a value of 0.39 µg/L. CONCLUSION: The presence and clinical significance of increased cobalt levels in 4 patients with the use of a modular dual mobility prosthesis demonstrates the necessity of continued surveillance.

Development of Plain Language Supplemental Materials for the Biobank Informed Consent Process.

The US Department of Health and Human Services addresses clear communication in the informed consent process as part of the Notice of Proposed Rulemaking for revisions to the Common Rule. However, prior research has shown that participants may not fully comprehend research studies despite completion of an informed consent process. Our main goal was to provide plain language information about donation processes to a cancer biobank to supplement an informed consent form. We developed and conducted cognitive testing with supplemental brochures that clearly communicated information about three different models for consent (notice, broad and study-specific) to future use of biospecimens. During the brochure development process, we conducted qualitative, semi-structured, individual, in-person cognitive interviews among 14 women to examine participants' perceptions of the brochures. Each participant provided feedback regarding the understandability, graphics and layout, and cultural appropriateness of the brochures. Our findings demonstrate that these methods may be used to tailor consent form brochures, such as the ones developed here, to other populations. This study therefore adds to our understanding of how best to present content to help women from two different racial groups make informed decisions about participation in a cancer biobank.

Overexpressed Gα13 activates serum response factor through stoichiometric imbalance with Gßγ and mislocalization to the cytoplasm.

Gα13, a heterotrimeric G protein α subunit of the G12/13 subfamily, is an oncogenic driver in multiple cancer types. Unlike other G protein subfamilies that contribute to cancer progression via amino acid substitutions that abolish their deactivating, intrinsic GTPase activity, Gα13 rarely harbors such mutations in tumors and instead appears to stimulate aberrant cell growth via overexpression as a wildtype form. It is not known why this effect is exclusive to the G12/13 subfamily, nor has a mechanism been elucidated for overexpressed Gα13 promoting tumor progression. Using a reporter gene assay for serum response factor (SRF)-mediated transcription in HEK293 cells, we found that transiently expressed, wildtype Gα13 generates a robust SRF signal, approximately half the amplitude observed for GTPase-defective Gα13. When epitope-tagged, wildtype Gα13 was titrated upward in cells, a sharp increase in SRF stimulation was observed coincident with a "spillover" of Gα13 from membrane-associated to a soluble fraction. Overexpressing G protein ß and γ subunits caused both a decrease in this signal and a shift of wildtype Gα13 back to the membranous fraction, suggesting that stoichiometric imbalance in the αßγ heterotrimer results in aberrant subcellular localization and signalling by overexpressed Gα13. We also examined the acylation requirements of wildtype Gα13 for signalling to SRF. Similar to GTPase-defective Gα13, S-palmitoylation of the wildtype α subunit was necessary for SRF activation but could be replaced functionally by an engineered site for N-terminal myristoylation. However, a key difference was observed between wildtype and GTPase-defective Gα13: whereas the latter protein lacking palmitoylation sites was rescued in its SRF signalling by either an engineered polybasic sequence or a C-terminal isoprenylation site, these motifs failed to restore signalling by wildtype, non-palmitoylated Gα13. These findings illuminate several components of the mechanism in which overexpressed, wildtype Gα13 contributes to growth and tumorigenic signalling, and reveal greater stringency in its requirements for post-translational modification in comparison to GTPase-defective Gα13.

Implementation of ultrasound after central venous catheter insertion: A qualitative study in early adopters.

BACKGROUND: The adoption rate of point of care ultrasound (POCUS) for the confirmation of central venous catheter (CVC) positioning and exclusion of post procedure pneumothorax is low despite advantages in workflow compared to traditional chest X-ray (CXR). To explore why, we convened focus groups to address barriers and facilitators of implementation for POCUS guided CVC confirmation and de-implementation of post-procedure CXR. METHODS: We conducted focus groups with emergency medicine and critical care providers to discuss current practices in POCUS for CVC confirmation. The semi-structured focus group interview guide was informed by the Consolidated Framework for Implementation Research (CFIR). We performed qualitative content analysis of the resulting transcripts using a consensual qualitative research approach (NVivo software), aiming to identify priority categories that describe the barriers and facilitators of POCUS guided CVC confirmation. RESULTS: The coding dictionary of barriers and facilitators consisted of 21 codes from the focus group discussions. Our qualitative analysis revealed that 12 codes emerged spontaneously (inductively) within the focus group discussions and aligned directly to CFIR constructs. Common barriers included provider influences (e.g. knowledge and beliefs about POCUS for CVC confirmation), external network (e.g. societal guidelines, ancillary staff, and consultants), and inertia (habit or reflexive processes). Common facilitators included ultrasound protocol advantage and champions. Time and provider outcomes (cognitive offload, ownership, and independence) emerged as early barriers but late facilitators. CONCLUSION: Our qualitative analysis demonstrates real and perceived barriers against implementation of POCUS for CVC position confirmation and pneumothorax exclusion. Our findings discovered organizational and personal constructs that will inform development of multifaceted strategies toward implementation of POCUS after CVC insertion.

Listener Age and Gender Diversity: Effects on Voice-based Perception of Gender.

OBJECTIVE: An important clinical outcome of voice masculinization treatments in transmasculine speakers is voice-based perception of gender. Rigorous assessments of voice treatment that utilize ratings of perception of gender typically do not control for demographic characteristics of the listeners. The objective of the present study was to determine the effect of listeners' age and gender diversity on voice-based judgments of speaker gender. METHODS: Speech stimuli were produced by a single transmasculine individual over approximately one year of hormone replacement therapy, during which he experienced significant changes in his voice. Three groups of listeners rated speech stimuli on a visual analog scale with anchors ranging from "definitely male" to "guessing male" to "guessing female" to "definitely female." Listener groups were N = 10 cisgender young adults, N = 10 cisgender older adults, and N = 10 gender diverse individuals. RESULTS: All groups rated the speaker as consistently female through week 14 of hormone replacement therapy and consistently male after week 28. Mean responses of the three groups of listeners were highly correlated (Pearson's correlations all r > 0.97). CONCLUSION: Given reasonable group sizes, average ratings of gender perception of a transmasculine speaker are not highly influenced by varying listener age and gender minority status.

Auditory-Motor Perturbations of Voice Fundamental Frequency: Feedback Delay and Amplification.

Purpose Gradual and sudden perturbations of vocal fundamental frequency (f o), also known as adaptive and reflexive f o perturbations, are techniques to study the influence of auditory feedback on voice f o control mechanisms. Previous vocal f o perturbations have incorporated varied setup-specific feedback delays and amplifications. Here, we investigated the effects of feedback delays (10-100 ms) and amplifications on both adaptive and reflexive f o perturbation paradigms, encapsulating the variability in equipment-specific delays (3-45 ms) and amplifications utilized in previous experiments. Method Responses to adaptive and reflexive f o perturbations were recorded in 24 typical speakers for four delay conditions (10, 40, 70, and 100 ms) or three amplification conditions (-10, +5, and +10 dB relative to microphone) in a counterbalanced order. Repeated-measures analyses of variance were carried out on the magnitude of f o responses to determine the effect of feedback condition. Results There was a statistically significant effect of the level of auditory feedback amplification on the response magnitude during adaptive f o perturbations, driven by the difference between +10- and -10-dB amplification conditions (hold phase difference: M = 38.3 cents, SD = 51.2 cents; after-effect phase: M = 66.1 cents, SD = 84.6 cents). No other statistically significant effects of condition were found for either paradigm. Conclusions Experimental equipment delays below 100 ms in behavioral paradigms do not affect the results of f o perturbation paradigms. As there is no statistically significant difference between the response magnitudes elicited by +5- and +10-dB auditory amplification conditions, this study is a confirmation that an auditory feedback amplification of +5 dB relative to microphone is sufficient to elicit robust compensatory responses for f o perturbation paradigms.

Influence of donor C3 allotype on late renal-transplantation outcome.

BACKGROUND: The complement system has a critical role in both the innate and the adaptive immune responses. In humans, C3 exists as two main allotypes, F (fast) and S (slow), which are known to affect the incidence of inflammatory disease. We conducted a study to address the influence of these alleles on late renal-graft outcome. METHODS: We determined the C3 allotypes of 662 pairs of adult kidney donors and recipients from 1993 through 2002 and then related C3F/S polymorphism status to demographic and clinical outcome data. The median length of follow-up was 3.3 years. RESULTS: Analysis of 513 pairs of white donors and recipients identified 113 C3S/S recipients of a C3S/F or a C3F/F kidney and 179 C3S/S recipients of a C3S/S kidney. Graft survival was significantly better with a C3F/F or C3F/S donor allotype than a C3S/S allotype (P=0.05). The hazard ratio for graft loss of C3S/S kidneys, as compared with C3F/F or C3F/S kidneys, was 2.21 (95 percent confidence interval, 1.04 to 4.72; P=0.04). The graft function of C3F/F or C3F/S donor kidneys was significantly better than that of C3S/S donor kidneys (P<0.001). The effect of the C3F allele was specific to recipients who did not themselves possess this allele. Multivariate analysis excluded effects of other factors known to influence graft outcome. CONCLUSIONS: Expression of C3 alleles by donor renal cells appears to have a differential effect on late graft outcome. Among white C3S/S recipients, receipt of a C3F/F or C3F/S donor kidney, rather than a C3S/S donor kidney, is associated with a significantly better long-term outcome. These findings suggest that the two alleles have functional differences.

Giving Voice to Black Men: Guidance for Increasing the Likelihood of Having a Usual Source of Care.

Black men suffer inequalities in health and health-care outcomes relative to other racial/ethnic groups, requiring well-informed efforts for health promotion. Fewer Black men have a usual source of health care, which may be a contributor to these disparities. Increasing access to and the likelihood of a usual source of care among Black men are important to address health and health-care disparities. In this focus group study, we sought to better understand how Black men think about primary care and usual sources of care. A total of six focus groups were conducted with N = 25 men. Groups were a mix of men with and without a usual source of care. Several themes were identified through analysis of the data regarding factors that contribute to Black men going to the doctor. Themes identified in the data analysis included Lack of Health Insurance as a Barrier to Establishing Usual Source of Care; Family Promoting Health Care Use; Relationship With Doctor, Trust, and Empowerment; Age and Maturity in Health Promotion; and Positive Tone of Messaging. Future research should explore if similar findings are obtained among men in different regions of the United States or between Black men of different backgrounds. Taking a step beyond this research, specifically, future research can also examine the impact of particular health messages/messaging on Black men's health-care-seeking behaviors.

Mechanisms of disease: the complement system in renal injury--new ways of looking at an old foe.

The fact that the complement system is activated during immune-complex glomerular disease has been known for nearly 50 years. Detection of complement deposition in the glomerulus using immunochemistry has become an important element of the histological analysis of renal biopsies, and is key to the diagnosis of many types of glomerulonephritis. In recent years it has become evident that complement activation is involved in the pathogenesis of other types of renal disease; complement activation is implicated in transplant injury, atypical hemolytic uremic syndrome and progressive tubulointerstitial fibrosis. Emergence of this evidence has provided insight into how these diseases develop, and has yielded useful diagnostic tools and potential targets for therapeutic intervention. Clinicians have, by using plasma-based therapies, unknowingly treated abnormalities of the complement system in renal patients for many years. Advances in antibody and protein technologies have led to the development of complement inhibitors that have been used in phase III clinical studies. More-specific agents and applications are likely to be developed over the coming years and are discussed in this Review.

Child abduction murder: an analysis of the effect of time and distance separation between murder incident sites on solvability.

Empirical studies of child abduction murder investigations are lacking. Accordingly, an empirical analysis of the effect of time and distance relationships on case solvability in child abduction murders (N=735) was conducted. The murders occurred across the United States from 1968 to 2002. Murder incident components examined were: victim last seen site, initial contact site, murder site, and body recovery site. Time and distance intervals between component pairings were also examined. Descriptive, bivariate, and multivariate analyses were performed to determine if information relating to time and distance intervals between components were critical solvability factors. Results show that information about time and distance increases case solvability. Results also demonstrate that time and distance relationships contribute uniquely to case solvability in murders of abducted children. Findings also indicate that additional factors such as type of forensic evidence, investigative resources, or actions by first responders, may be critical to case solvability.

Diagnosing and managing cutaneous pigmented lesions: primary care physicians versus dermatologists.

BACKGROUND: Primary care physicians (PCPs) are often expected to screen for melanomas and refer patients with suspicious pigmented lesions to dermatologists. OBJECTIVE: To assess whether there is a difference between dermatologists and PCPs in accurately diagnosing melanoma and appropriately managing (based on decisions to refer/biopsy) suspicious pigmented lesions. DESIGN, PARTICIPANTS: A survey based on a random sample of 30 photographs of pigmented lesions with known pathology was administered to 101 dermatologists and 115 PCPs from October 2001 to January 2003. MEASUREMENTS: Likelihoods that a photographed lesion was melanoma and that the lesion should be biopsied/referred were scored on a 1 to 10 scale. Accuracy of melanoma diagnosis and appropriateness of pigmented lesion management were compared between dermatologists and PCPs by using the areas under (AUC) the receiver operating characteristic (ROC) curves. RESULTS: Dermatologists were superior to PCPs in diagnosing melanomas (AUC 0.89 vs 0.80, P<.001) and appropriately managing pigmented lesions (AUC .84 vs 0.76, P<.001). PCPs who tended to biopsy lesions themselves did better at managing pigmented lesions than PCPs who did not perform biopsies. Dermatology training during residency did not significantly improve the diagnostic accuracy of PCPs nor their management of pigmented lesions. CONCLUSIONS: Dermatologists have both better diagnostic accuracy and ability to manage pigmented lesions than PCPs. Yet, there is a shortage of dermatologists to meet the demand of accurate melanoma screening. More innovative strategies are needed to better train PCPs and enhance skin cancer screening.

Roles of Occupational Therapists in Theater, Past and Present.

The impetus to deploy occupational therapy (OT) assets into theaters of operation lies in the occupational therapist's ability to evaluate the effect of physical and/or behavioral symptoms on functional performance and effectively develop individualized interventions. Occupational therapy utilization has been robust during 14 years of continuous deployments in Iraq and Afghanistan. Occupational therapy's indoctrinated role in combat is solely with the combat and operational stress control missions, however, the skills and capabilities of this profession have demonstrated efficacy in other specializations, including concussion care. The effectiveness of OT interventions is demonstrated with improved return to duty (RTD) rates for casualties suffering with combat and operational stress reactions where OT was a major component of a restoration and reconditioning program. As well, postconcussion RTD rates have been linked to the broad skill sets inherent in OT that allow casualties to remain in theater from the point of injury to complete recovery and RTD.

Systematic assessment of the influence of complement gene polymorphisms on kidney transplant outcome.

The importance of the innate immune system, including complement, in causing transplant injury and augmenting adaptive immune responses is increasingly recognized. Therefore variability in graft outcome may in part be due to genetic polymorphism in genes encoding proteins of the immune system. This study assessed the relationship between single nucleotide polymorphisms (SNPs) in complement genes and outcome after transplantation. Analysis was performed on two patient cohorts of 650 and 520 transplant recipients. 505 tagged SNPs in 47 genes were typed in both donor and recipient. The relationships between SNPs and graft survival, serum creatinine, delayed graft function and acute rejection were analyzed. One recipient SNP in the gene encoding mannose binding lectin was associated with graft outcome after correction for analysis of multiple SNPs (p=6.41 × 10(-5)). When further correction was applied to account for analysis of the effect of SNPs in both donor and recipient this lost significance. Despite association p values of <0.001 no SNP was significantly associated with clinical phenotypes after Bonferroni correction. In conclusion, the variability seen in transplant outcome in this patient cohort cannot be explained by variation in complement genes. If causal genetic effects exist in these genes, they are too small to be detected by this study.

Differences in preferences for models of consent for biobanks between Black and White women.

Biobanks are essential resources, and participation by individuals from diverse groups is needed. Various models of consent have been proposed for secondary research use of biospecimens, differing in level of donor control and information received. Data are needed regarding participant preferences for models of consent, particularly among minorities. We conducted qualitative semi-structured interviews with 60 women to examine their attitudes about different models of consent. Recruitment was stratified by race (Black/White) and prior biobank participation (yes/no). Two coders independently coded interview transcripts. Qualitative thematic analysis was conducted using NVivo 10. The majority of Black and White participants preferred "broad" consent (i.e., blanket permission for secondary research use of biospecimens), and the second most preferred model for both groups was "study-specific" consent (i.e., consent for each future research study). The qualitative analysis showed that participants selected their most preferred model for 3 major reasons: having enough information, having control over their sample, and being asked for permission. Least preferred was notice model (i.e., participants notified that biospecimens may be used in future research). Attitudes toward models of consent differed somewhat by race and prior biobank participation. Participants preferred models of consent for secondary research use of biospecimens that provided them with both specific and general information, control over their biospecimens, and asked them to give permission for use. Our findings suggest that it will be important for researchers to provide information about future uses of biospecimens to the extent possible and have an explicit permission step for secondary research use.

Child abduction murder: the impact of forensic evidence on solvability.

This study examined 733 child abduction murders (CAMs) occurring from 1968 to 2002 to explore the influence of forensic evidence on case solvability in CAM investigations. It was hypothesized that the presence of forensic evidence connecting the offender to the crime would enhance case solvability in murder investigations of abducted children. This study examined the impact of CAM of different types of forensic evidence and the impact of the summed total of forensic evidence items on case solvability by controlling for victim age, victim race, victim gender, and victim-offender relationship. Time and distance theoretical predictors were also included. Binomial logistic regression models were used to determine whether forensic evidence was a critical solvability factor in murder investigations of abducted children. This research indicated that, while forensic evidence increased case solvability, the impact of forensic evidence on solvability was not as important as other solvability factors examined.