Antibodies expand the scope of angiotensin receptor pharmacology.

G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue and cellular levels. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized. Here, using protein engineering, pharmacological assays and structural studies, we develop maternally selective heavy-chain-only antibody ('nanobody') antagonists against the angiotensin II type I receptor and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to angiotensin II type I receptor with specific small-molecule antagonists and demonstrate that ligand selectivity can be readily tuned. Our work illustrates that antibody fragments can exhibit rich and evolvable pharmacology, attesting to their potential as next-generation GPCR modulators.

Impact of Telemedicine on Access to Care for Rural Transgender and Gender-Diverse Youth.

OBJECTIVE: To explore the impact of telemedicine on access to gender-affirming care for rural transgender and gender diverse youth. STUDY DESIGN: A retrospective analysis of data drawn from the electronic medical records of a clinic that provides approximately 10 000 adolescent and young adult visits per year and serves patients seeking gender health care. The no-show rate was examined as a proxy for access to care due to anticipated challenges with recruiting a representative sample of a historically marginalized population. Logistic regression with generalized estimating equations was conducted to model the association between the odds of a no-show visit and covariates of interest. RESULTS: Telemedicine visits, rural home address, gender health visits, longer travel time, and being younger than 18 years old were associated with lower odds of a no-show in univariate models (n = 17 928 visits). In the adjusted model, the OR of no-shows for gender health visits was 0.56 (95% CI 0.42-0.74), adjusting for rurality, telemedicine, age (< or >18 years), and travel time to the clinic. CONCLUSIONS: In this study, telemedicine was associated with reduced no-shows overall, and especially for rural, transgender and gender diverse youth, and patients who hold both identities. Although the no-show rate does not fully capture barriers to access, these findings provide insight into how this vulnerable population may benefit from expanded access to telemedicine for rural individuals whose communities may lack providers with the skills to serve this population.

Progesterone therapy for prevention of recurrent spontaneous preterm birth in a minority patient population: a retrospective study.

BACKGROUND: Preterm birth is a leading cause of infant morbidity and mortality worldwide. The burden of prematurity underscores the need for effective risk reduction strategies. The purpose of this study is to evaluate the efficacy of progesterone therapy, both intramuscular 17-α-hydroxyprogesterone caproate (IM 17-OHPC) and vaginal progesterone, in the prevention of recurrent spontaneous preterm birth (sPTB). The co-primary outcomes included: recurrent spontaneous PTB < 37 and < 34 weeks' gestation. METHODS: This retrospective cohort study included 637 pregnant patients that delivered at any of the three hospitals within the Los Angeles County healthcare system between October 2015 and June 2021. We compared frequencies of measured variables between each of the progesterone treated groups to no treatment using Pearson chi-squared tests and independent t-tests for categorical and continuous variables, respectively. We estimated crude and adjusted associations between each specific treatment (versus no treatment) and primary outcomes using logistic regression. RESULTS: Recurrent sPTB < 37 weeks' gestation occurred in 22.3% (n = 64) of those in the no treatment group, 29.1% (n = 86, p = .077) in the 17-OHPC group, and 14.3% (n = 6, p = 0.325) in the vaginal progesterone group. Recurrent sPTB < 34 weeks' gestation was 6.6% (n = 19) in the no treatment group, 11.8% (n = 35, p = .043) in the 17-OHPC group, and 7.1% (n = 3, p = 1) in the vaginal progesterone group. Among all participants, neither 17-OHPC nor vaginal progesterone was significantly associated with a reduction in recurrent sPTB at any time point. Among those with a short cervix, IM 17-OHPC was positively associated with recurrent sPTB < 37 weeks' gestation (aOR 5.61; 95% CI 1.16, 42.9). CONCLUSIONS: Progesterone therapy of any type did not reduce the risk of recurrent sPTB < 34 or < 37 weeks' gestation compared to no progesterone therapy.

Assessing the efficacy of magnesium oxide and riboflavin as preventative treatment of migraines in pregnancy.

PURPOSE: The purpose of this study is to assess the efficacy of magnesium oxide (MgO) alone and, secondarily, MgO plus riboflavin as preventive treatment of migraines in pregnancy. We hypothesize that MgO alone will be effective for the majority of patients and, when clinically indicated, the addition of riboflavin will result in further benefit. METHODS: This was a retrospective cohort study of pregnant patients treated for migraines between 2015 and 2020. We evaluated pre-/post-differences in the following primary outcomes: migraine frequency, severity, and duration. Secondary outcomes included associated migraine symptoms. RESULTS: Of 203 total patients, 117 received MgO alone and 86 received MgO plus riboflavin. There were no significant differences in baseline demographics between the two groups. There was a statistically significant decrease in migraine frequency, severity, and duration in the groups receiving MgO alone and MgO plus riboflavin (p < 0.01 for all). In total, 154 patients reported migraine-associated symptoms, of which 119 (77%) improved after treatment, 18 (12%) did not improve, and 17 (11%) patients' data were missing. The MgO plus riboflavin group had a lower gestational age at treatment initiation and was more likely to receive treatment prior to pregnancy (p < 0.01). Significant differences were observed for several baseline migraine symptoms, including photophobia, phonophobia, nausea, and vomiting, which were more common in the group receiving MgO plus riboflavin (p < 0.05 for all). CONCLUSION: Migraine frequency, severity, and duration all decreased with MgO alone and MgO plus riboflavin in this pregnancy cohort. Associated symptoms also significantly decreased for both groups.

Rapid changes in coastal ocean microbiomes uncoupled with shifts in environmental variables.

Disturbances, here defined as events that directly alter microbial community composition, are commonly studied in host-associated and engineered systems. In spite of global change both altering environmental averages and increasing extreme events, there has been relatively little research into the causes, persistence and population-level impacts of disturbance in the dynamic coastal ocean. Here, we utilize 3 years of observations from a coastal time series to identify disturbances based on the largest week-over-week changes in the microbiome (i.e. identifying disturbance as events that alter the community composition). In general, these microbiome disturbances were not clearly linked to specific environmental factors and responsive taxa largely differed, aside from SAR11, which generally declined. However, several disturbance metagenomes identified increased phage-associated genes, suggesting that unexplained community shifts might be caused by increased mortality. Furthermore, a category 1 hurricane, the only event that would likely be classified a priori as an environmental disturbance, was not an outlier in microbiome composition, but did enhance a bloom in seasonally abundant phytoplankton. Thus, as extreme environmental changes intensify, assumptions of what constitutes a disturbance should be re-examined in the context of ecological history and microbiome responses.

Sex-related differences in pattern of ethanol drinking under the intermittent-access model and its impact on exploratory and anxiety-like behavior in Long-Evans rats.

BACKGROUND: While men in the United States consume more alcohol than women, rates of drinking are converging. Nevertheless, females remain underrepresented in preclinical alcohol research. Here, we examined rats' sex-related differences in patterns of ethanol (EtOH) drinking and the effects of this drinking on exploratory and anxiety-like behavior. METHODS: Adult male and female Long-Evans rats were given 20% ethanol under the intermittent-access two-bottle-choice paradigm. Their intake was measured daily for the first 7 weeks. During the eighth week, intake was measured over the 24 h of daily access. During the ninth week, they, along with EtOH-naive controls, were tested prior to daily access in a novel chamber, light-dark box, and hole board apparatus. During the tenth week, blood ethanol concentration (BEC) was assessed after 30 to 40 min of access. RESULTS: Females overall demonstrated higher ethanol intake and preference across all access weeks than males, although only half of females drank significantly more than males. Across 24 h of daily access, both sexes had their highest intake in the first 30 min and their lowest in the middle of the light phase of the light/dark cycle. Despite their greater ethanol intake, females did not show significantly different BECs than males. In behavioral tests, females showed less vertical time in a novel activity chamber, more movement between chambers in a light-dark box, and more nose pokes in a hole-board apparatus than males. While a history of ethanol drinking led to a trend for lower vertical time in the activity chamber and greater chamber entries in the light-dark box, the effects were not sex-dependent. CONCLUSIONS: These results suggest that female and male rats could both be tested for acute effects of ethanol after 30 min of daily access, but that nuanced considerations are needed in the design of these experiments and the interpretation of their findings.

Anesthesiologist Age and Sex Influence Patient Perceptions of Physician Competence.

BACKGROUND: Uncovering patients' biases toward characteristics of anesthesiologists may inform ways to improve the patient-anesthesiologist relationship. The authors previously demonstrated that patients prefer anesthesiologists displaying confident body language, but did not detect a sex bias. The effect of anesthesiologists' age on patient perceptions has not been studied. In this follow-up study, it was hypothesized that patients would prefer older-appearing anesthesiologists over younger-appearing anesthesiologists and male over female anesthesiologists. METHODS: Three hundred adult, English-speaking patients were recruited in the Preanesthesia Evaluation and Testing Center. Patients were randomized (150 per group) to view a set of four videos in random order. Each 90-s video featured an older female, older male, younger female, or younger male anesthesiologist reciting the same script describing general anesthesia. Patients ranked each anesthesiologist on confidence, intelligence, and likelihood of choosing the anesthesiologist to care for their family member. Patients also chose the one anesthesiologist who seemed most like a leader. RESULTS: Three hundred patients watched the videos and completed the questionnaire. Among patients younger than age 65 yr, the older anesthesiologists had greater odds of being ranked more confident (odds ratio, 1.92; 95% CI, 1.41 to 2.64; P < 0.001) and more intelligent (odds ratio, 2.24; 95% CI, 1.62 to 3.11; P < 0.001), and had greater odds of being considered a leader (odds ratio, 2.62; 95% CI, 1.72 to 4.00; P < 0.001) when compared with younger anesthesiologists. The preference for older anesthesiologists was not observed in patients age 65 and older. Female anesthesiologists had greater odds of being ranked more confident (odds ratio, 1.46; 95% CI, 1.13 to 1.87; P = 0.003) and more likely to be chosen to care for one's family member (odds ratio, 1.80; 95% CI, 1.40 to 2.31; P < 0.001) compared with male anesthesiologists. The ranking preference for female anesthesiologists on these two measures was observed among white patients and not among nonwhite patients. CONCLUSIONS: Patients preferred older anesthesiologists on the measures of confidence, intelligence, and leadership. Patients also preferred female anesthesiologists on the measures of confidence and likelihood of choosing the anesthesiologist to care for one's family member.

Effects of pituitary adenylate cyclase-activating polypeptide isoforms in nucleus accumbens subregions on ethanol drinking.

While limited research has implicated the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in problematic alcohol use, the brain regions and isoforms involved in this effect remain to be determined. One region that has been found both to exhibit PACAP binding and, separately, to be involved in ethanol drinking is the nucleus accumbens (NAc). Thus, this study sought to characterize the effect of the PACAP isoforms in the NAc on ethanol drinking under the intermittent-access two-bottle-choice paradigm, in male and female Long-Evans rats. With microinjection into the medial NAc shell, PACAP-27 but not PACAP-38 was found to dose-dependently reduce binge-like ethanol drinking. In contrast, the PACAP receptor antagonist, PACAP (6-27), but not PACAP (6-38), enhanced ethanol drinking. This effect of PACAP was substance specific, as neither isoform in the NAc shell affected binge-like sucrose drinking. It was also anatomically specific, as PACAP-38 rather than PACAP-27 suppressed ethanol drinking when injected into the NAc core, and PACAP-27 instead enhanced drinking when injected into the caudal third of the medial NAc shell. Finally, while PACAP-38 in the NAc shell affected stress-related exploratory behavior, reducing time spent in the light chamber of a light-dark box, PACAP-27 did not significantly affect behavior in a light-dark box or open field. Together, these results, showing that PACAP-27 in the NAc shell attenuates binge-like ethanol drinking without affecting select stress-related behaviors, suggest that compounds related to this PACAP isoform should be investigated as potential novel therapeutics for the treatment of alcohol use disorder.

Narrative frames as choice over structure of American Indian sexual and reproductive health consequences of historical trauma.

Emerging evidence suggests that the historical trauma associated with settler colonialism affects the sexual and reproductive health (SRH) of American Indian (AI) communities today. This article examines how one AI community narratively frames the influence of historical trauma within the context of community-based participatory research (CBPR) and the implications of this framing for health behaviours, internalized oppression, SRH outcomes, and future CBPR interventions. We found that AIs framed the SRH consequences of historical trauma with renderings that favoured personal choice over structural explanations. Our findings suggest future interventions could: (1) include educational components on historical trauma and the continued role settler colonialism plays in structural violence against AI bodies and communities; and (2) recognize the role that the individualized logic of westernized/white culture may play in the erasure of traditional collectivist AI culture, internalized oppression, and SRH.

Rational Ligand Design Enables pH Control over Aqueous Iron Magnetostructural Dynamics and Relaxometric Properties.

Complexes of Fe3+ engage in rich aqueous solution speciation chemistry in which discrete molecules can react with solvent water to form multinuclear µ-oxo and µ-hydroxide bridged species. Here we demonstrate how pH- and concentration-dependent equilibration between monomeric and µ-oxo-bridged dimeric Fe3+ complexes can be controlled through judicious ligand design. We purposed this chemistry to develop a first-in-class Fe3+-based MR imaging probe, Fe-PyCy2AI, that undergoes relaxivity change via pH-mediated control of monomer vs dimer speciation. The monomeric complex exists in a S = 5/2 configuration capable of inducing efficient T1-relaxation, whereas the antiferromagnetically coupled dimeric complex is a much weaker relaxation agent. The mechanisms underpinning the pH dependence on relaxivity were interrogated by using a combination of pH potentiometry, 1H and 17O relaxometry, electronic absorption spectroscopy, bulk magnetic susceptibility, electron paramagnetic resonance spectroscopy, and X-ray crystallography measurements. Taken together, the data demonstrate that PyCy2AI forms a ternary complex with high-spin Fe3+ and a rapidly exchanging water coligand, [Fe(PyCy2AI)(H2O)]+ (ML), which can deprotonate to form the high-spin complex [Fe(PyCy2AI)(OH)] (ML(OH)). Under titration conditions of 7 mM Fe complex, water coligand deprotonation occurs with an apparent pKa 6.46. Complex ML(OH) dimerizes to form the antiferromagnetically coupled dimeric complex [(Fe(PyCy2AI))2O] ((ML)2O) with an association constant (Ka) of 5.3 ± 2.2 mM-1. The relaxivity of the monomeric complexes are between 7- and 18-fold greater than the antiferromagnetically coupled dimer at applied field strengths ranging between 1.4 and 11.7 T. ML(OH) and (ML)2O interconvert rapidly within the pH 6.0-7.4 range that is relevant to human pathophysiology, resulting in substantial observed relaxivity change. Controlling Fe3+ µ-oxo bridging interactions through rational ligand design and in response to local chemical environment offers a robust mechanism for biochemically responsive MR signal modulation.

A Canadian-wide perspective on the essential conditions for taking a comprehensive school health approach.

BACKGROUND: The primary purpose of this research was to explore Comprehensive School Health (CSH) stakeholders' perceptions of the essential conditions for taking a CSH approach in other contexts across Canada. The secondary purpose was to examine the need for and development of an evaluative tool or resource to assess the implementation of the essential conditions. METHODS: Data were generated through individual semi-structured interviews (n = 38) and small group interviews (n = 3) with 45 participants across Canada involved in implementing policies or programs which take a CSH approach. Interviews were subjected to content analysis. RESULTS: There was positive support for the essential conditions and results indicated the essential conditions are relevant across Canada. Findings revealed the necessity for a new essential condition that reflected support and leadership from the school district and/or provincial/territorial governing bodies. Modifications to the description of each of the essential conditions were also suggested to provide clarity. Results also indicated that an evaluative tool that was concise, meaningful, and provided immediate feedback would be useful to school communities to establish readiness, assess, and improve ongoing implementation of CSH approaches. CONCLUSIONS: This research contributes to the evidence-base of CSH by providing school communities across Canada with a set of refined and understandable essential conditions that support successful implementation. Further, the development of an evaluation tool will support school health champions, researchers, and policymakers in the optimization and implementation of policies or programs which take a CSH approach, ultimately supporting healthier school communities across the country.

Electrocardiographic left atrial abnormality in patients presenting with ischemic stroke.

BACKGROUND: P wave indices represent electrocardiographic marker of left atrial pathology. We hypothesized that P wave would be more abnormal in patients presenting with ischemic stroke than a comparable group without ischemic stroke. METHODS: We compared P wave terminal force in V1 (PTFV1) between patients admitted with ischemic stroke (case) and patients followed in cardiology clinic (control) at a single medical center. Using logistic regression models, we tested for an association between abnormal PTFV1 (> 4000 µV ms) and ischemic stroke. We also defined several optimal cut-off values of PTFV1 using a LOESS plot and estimated odds ratio of ischemic stroke when moving from one cut-point level to the next higher-level. RESULTS: A total of 297 patients (case 147, control 150) were included. PTFV1 was higher in patients with vs. those without ischemic stroke (median 4620 vs 3994 µV ms; p=0.006). PTFV1 was similar between cardioembolic/cryptogenic and other stroke subtypes. In multivariable analyses adjusting for sex, obesity, age, and hypertension, the association between abnormal PTFV1 and ischemic stroke ceased to be significant (OR 1.53 [0.95, 2.50], p=0.083). Increase to the next cutoff level of PTFV1 (900, 2000, 3000, 4000, 5000, and 6000 µV ms) was associated with 18% increase in odds of having ischemic stroke (vs. no ischemic stroke) (OR 1.18 [1.02, 1.36], p=0.026). CONCLUSION: Patients presenting with acute ischemic stroke are more likely to have abnormal PTFV1. These findings from a real-world clinical setting support the results of cohort studies that left atrial pathology manifested as abnormal PTFV1 is associated with ischemic stroke.

Influence of Sex and Body Language on Patient Perceptions of Anesthesiologists.

BACKGROUND: Patient perception of physician competence is important. The role of body language and physician sex on patient perceptions has not been investigated. The authors hypothesized that patients perceive anesthesiologists displaying confident body language as more competent and that patients would prefer male anesthesiologists. METHODS: Two hundred adult patients presenting to the Preanesthesia Evaluation and Testing Center at the University of Virginia Health System were recruited to participate using consecutive sampling. Patients viewed four 90-s videos in random order. Each video featured a male or female actor displaying confident, high-power poses or unconfident, low-power poses. Each actor recited the same script describing general anesthesia. Patients were randomized (100 per group) to view one of two sets of videos to account for any actor preferences. Participants ranked each actor anesthesiologist on perceived confidence, intelligence, and likelihood of choosing that anesthesiologist to care for their family member. Participants also chose the one actor anesthesiologist who seemed most like a leader. RESULTS: Two hundred patients watched the videos and completed the questionnaire. Actor anesthesiologists displaying confident, high-power body language had greater odds of being ranked as more confident (odds ratio, 2.27; 95% CI, 1.76 to 2.92; P < 0.0001), more intelligent (odds ratio, 1.69; 95% CI, 1.13 to 2.18; P < 0.0001), more likely chosen to care for one's family member (odds ratio, 2.34; 95% CI, 1.82 to 3.02; P < 0.0001), and more likely to be considered a leader (odds ratio, 2.60; 95% CI, 1.86 to 3.65; P < 0.0001). Actor anesthesiologist sex was not associated with ranking for any response measures. CONCLUSIONS: Patients perceive anesthesiologists displaying confident body language as more confident, more intelligent, more like a leader, and are more likely to choose that anesthesiologist to care for their family member. Differences in patient perceptions based on sex of the anesthesiologist were not detected.

Neurotensin in the posterior thalamic paraventricular nucleus: inhibitor of pharmacologically relevant ethanol drinking.

Individuals prone to ethanol overconsumption may have preexisting neurochemical disturbances that contribute to their vulnerability. This study examined the paraventricular nucleus of the thalamus (PVT), a limbic structure recently shown to participate in ethanol intake. To identify individuals prone to ethanol overconsumption, we tested Long-Evans rats in behavioral paradigms and found high levels of vertical time (rearing behavior) in a novel activity chamber to be a consistent predictor of subsequent excessive 20 percent ethanol drinking under the intermittent access model. Examining neurochemicals in the PVT, we found before ethanol exposure that prone rats with high rearing, compared with non-prone rats, had significantly lower levels of neurotensin (NTS) mRNA and peptide in the posterior (pPVT) but not anterior (aPVT) subregion of the PVT. Our additional finding that ethanol intake has no significant impact on either rearing or NTS levels indicates that these measures, which are different in prone rats before ethanol consumption, remain stable after ethanol consumption. The possibility that NTS directly controls ethanol drinking is supported by our finding that NTS administration specifically suppresses ethanol drinking when injected into the pPVT but not aPVT, with this effect occurring exclusively in higher drinkers that presumably have lower endogenous levels of NTS. Further, an NTS antagonist in the pPVT augments intake in lower drinkers with presumably more endogenous NTS, while NTS in the pPVT inhibits novelty-induced rearing that predicts excessive drinking. Together, these results provide strong evidence that low endogenous levels of NTS in the pPVT contribute to an increased propensity toward excessive ethanol drinking.

Pituitary Adenylate Cyclase-Activating Polypeptide-27 (PACAP-27) in the Thalamic Paraventricular Nucleus Is Stimulated by Ethanol Drinking.

BACKGROUND: The paraventricular nucleus of the thalamus (PVT) is a limbic brain structure that affects ethanol (EtOH) drinking, but the neurochemicals transcribed in this nucleus that may participate in this behavior have yet to be fully characterized. The neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), is known to be transcribed in other limbic areas and to be involved in many of the same behaviors as the PVT itself, possibly including EtOH drinking. It exists in 2 isoforms, PACAP-38 and PACAP-27, with the former expressed at higher levels in most brain regions. The purpose of this study was to characterize PACAP in the PVT and to assess its response to EtOH drinking. METHODS: First, EtOH-naïve, Sprague Dawley rats were examined using quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry, to characterize PACAP mRNA and peptide throughout the rostrocaudal axis of the PVT. Next, EtOH-naïve, vGLUT2-GFP transgenic mice were examined using immunohistochemistry, to identify the neurochemical phenotype of the PACAPergic cells in the PVT. Finally, Long Evans rats were trained to drink 20% EtOH under the intermittent-access paradigm and then examined with PCR and immunohistochemistry, to determine the effects of EtOH on endogenous PACAP in the PVT. RESULTS: Gene expression of PACAP was detected across the entire PVT, denser in the posterior than the anterior portion of this nucleus. The protein isoform, PACAP-27, was present in a high percentage of cell bodies in the PVT, again particularly in the posterior portion, while PACAP-38 was instead dense in fibers. All PACAP-27+ cells colabeled with glutamate, which itself was identified in the majority of PVT cells. EtOH drinking led to an increase in PACAP gene expression and in levels of PACAP-27 in individual cells of the PVT. CONCLUSIONS: This study characterizes the PVT neuropeptide, PACAP, and its understudied protein isoform, PACAP-27, and demonstrates that it is involved in pharmacologically relevant EtOH drinking. This indicates that PACAP-27 should be further investigated for its possible role in EtOH drinking.

Operative and Oncologic Outcomes in 9861 Patients with Operable Breast Cancer: Single-Institution Analysis of Breast Conservation with Oncoplastic Reconstruction.

BACKGROUND: Oncoplastic reconstruction is an approach that enables patients with locally advanced or adversely located tumors to undergo breast conserving surgery (BCS). The objectives were to identify the use of BCS with oncoplastic reconstruction (BCS + R) and determine the operative and oncologic outcomes compared with other breast surgical procedures for breast cancer. METHODS: This retrospective cohort study interrogated a single institution's prospectively maintained databases to identify patients who underwent surgery for breast cancer between 2007 and 2014. Surgeries were categorized as BCS, BCS + R, total mastectomy (TM), or TM with immediate reconstruction (TM + R). Demographic and clinicopathologic characteristics and postoperative complications were analyzed. RESULTS: There were 10,607 operations performed for 9861 patients. Median follow-up was 3.4 years (range, 0-9.1 years). The use of BCS + R had a nearly fourfold increase in the percentage of all breast cancer surgeries during the study period; 75 % of patients who underwent BCS + R had a T1 or T2 tumor. There was no difference in the use of BCS + R compared with BCS for any quadrant of the breast except the lower outer quadrant (11.1 vs. 6.8 %; p < .0001). BCS + R had a lower rate of seroma formation (13.4 vs. 18 %; p = .002) and positive or close margins compared with BCS (5.8 vs. 8.3 %; p = .04). There was no difference in overall survival or recurrence-free survival when comparing BCS and BCS + R. CONCLUSIONS: Patients undergoing BCS + R are not disadvantaged in terms of complications and short-term (3-year) outcomes compared with BCS patients or patients who underwent TM.

Exploring the process of capacity-building among community-based health promotion workers in Alberta, Canada.

Community capacity-building is a central element to health promotion. While capacity-building features, domains and relationships to program sustainability have been well examined, information on the process of capacity-building as experienced by practitioners is needed. This study examined this process as experienced by coordinators working within a community-based chronic disease prevention project implemented in four communities in Alberta (Canada) from 2005-2010 using a case study approach with a mixed-method design. Data collection involved semi-structured interviews, a focus group and program documents tracking coordinator activity. Qualitative analysis followed the constant comparative method using open, axial and selective coding. Quantitative data were analyzed for frequency of major activity distribution. Capacity-building process involves distinct stages of networking, information exchange, partnering, prioritizing, planning/implementing and supporting/ sustaining. Stages are incremental though not always linear. Contextual factors exert a great influence on the process. Implications for research, practice and policy are discussed.