A Good Place to Do Time? Detailing the Construction of Symbolic Social Boundaries in Correctional Boot Camps.

Drawing on qualitative interviews with 51 incarcerated adult men and nine correctional officers in a Western Canadian prison system, we ask why some incarcerated people find it appealing to be placed on correctional boot camp units and what such appeals tell us about broader conditions of incarceration. Participants on three boot camp units drew on narratives relating to (a) extrinsic benefits, (b) discipline and structure, (c) teamwork and positive relationships, and (d) an opportunity for self-improvement to construct symbolic boundaries between "normal" units and boot camps, as well as their former self and their transformed current self. By drawing symbolic boundaries between the past and present and between other units and their boot camp unit, our participants create narratives that allow them to partially mitigate some pains of imprisonment.

Peristalsis prevents ureteral dilation.

PURPOSE: The etiology of ureteral dilation in primary nonrefluxing, nonobstructing megaureters is still not well understood. Impaired ureteral peristalsis has been theorized as one of the contributing factors. However, ureteral peristalsis and its "normal" function is not well defined. In this study, using mathematical modeling techniques, we aim to better understand how ureteral peristalsis works. This is the first model to consider clinically observed, back-and-forth, cyclic wall longitudinal motion during peristalsis. We hypothesize that dysfunctional ureteral peristalsis, caused by insufficient peristaltic amplitudes (e.g., circular muscle dysfunction) and/or lack of ureteral wall longitudinal motion (e.g., longitudinal muscle dysfunction), promotes peristaltic reflux (i.e., retrograde flow of urine during an episode of peristalsis) and may result in urinary stasis, urine accumulation, and consequent dilation. METHODS: Based on lubrication theory in fluid mechanics, we developed a two-dimensional (planar) model of ureteral peristalsis. In doing so, we treated ureteral peristalsis as an infinite train of sinusoidal waves. We then analyzed antegrade and retrograde flows in the ureter under different bladder-kidney differential pressure and peristalsis conditions. RESULTS: There is a minimum peristaltic amplitude required to prevent peristaltic reflux. Ureteral wall longitudinal motion decreases this minimum required amplitude, increasing the nonrefluxing range of peristaltic amplitudes. As an example, for a normal bladder-kidney differential pressure of 5 cmH2 O, ureteral wall longitudinal motion increases nonrefluxing range of peristaltic amplitude by 65%. Additionally, ureteral wall longitudinal motion decreases refluxing volumetric flow rates. For a similar normal bladder pressure example of 5 cmH2 O, refluxing volumetric flow rate decreases by a factor of 18. Finally, elevated bladder pressure, not only increases the required peristaltic amplitude for reflux prevention but it increases maximum refluxing volumetric flow rates. For the case without wall longitudinal motion, as bladder-kidney differential pressure increases from 5 to 40 cmH2 O, minimum required peristaltic amplitude to prevent reflux increases by 40% while the maximum refluxing volumetric flow rate increases by approximately 100%. CONCLUSION: The results presented in this study show how abnormal ureteral peristalsis, caused by the absence of wall longitudinal motion and/or lack of sufficient peristaltic amplitudes, facilitates peristaltic reflux and retrograde flow. We theorize that this retrograde flow can lead to urinary stasis and urine accumulation in the ureters, resulting in ureteral dilation seen on imaging studies and elevated infection risk. Our results also show how chronically elevated bladder pressures are more susceptible to such refluxing conditions that could lead to ureteral dilation.

The Floating Signifier of 'Safety': Correctional Officer Perspectives on COVID-19 Restrictions, Legitimacy and Prison Order.

The COVID-19 pandemic continues to affect prisons internationally. Existing research focuses on infection data, meaning we do not fully understand how COVID-19 shapes frontline prison dynamics. We draw on qualitative interviews with 21 Canadian federal correctional officers, exploring how the pandemic impacted prison management. Officers suggested inconsistent messaging around COVID-19 protocols reduced institutional and officers' self-legitimacy, fracturing trust relationships with incarcerated people. Furthermore, officers suggest that personal protective equipment such as gowns and face shields took on multiple meanings. We use Lévi-Strauss' floating signifier concept to analyse how individual definitions of 'safety' informed day-to-day prison routines. We conclude by arguing that legitimacy deficits and contested definitions of 'safety' will continue to create uncertainty, impacting prison operations going forward.

Pressure Measurement in a Bladder Phantom Using Contrast-Enhanced Ultrasonography-A Path to a Catheter-Free Voiding Cystometrogram.

OBJECTIVES: The long-term goal of this study is to investigate the efficacy of a novel, ultrasound-based technique called subharmonic-aided pressure estimation (SHAPE) to measure bladder pressure as a part of a cystometrogram (CMG) in a urodynamic test (ie, pressure-flow study). SHAPE is based on the principle that subharmonic emissions from ultrasound contrast microbubbles (MBs) decrease linearly with an increase in ambient pressure. We hypothesize that, using the SHAPE technique, we can measure voiding bladder pressure catheter-free. This is of importance because the CMG catheter, due to its space-occupying property and non-physiological effects, can undermine the reliability of the test during voiding and cause misdiagnosis. In this study, we tested this hypothesis and optimized the protocol in a controlled benchtop environment. MATERIALS AND METHODS: A bladder phantom was designed and built, capable of simulating clinically relevant bladder pressures. Laboratory-made lipid-shelled MBs (similar in composition to the commercial agent, DEFINITY) was diluted in 0.9% normal saline and infused into the bladder phantom using the CMG infusion system. A typical simulated CMG consists of 1 filling and 4 post-filling events. During CMG events, the bladder phantom is pressurized multiple times at different clinically relevant levels (small, medium, and large) to simulate bladder pressures. Simultaneous with pressurization, MB subharmonic signal was acquired. For each event, the change in MB subharmonic amplitude was correlated linearly with the change in bladder phantom pressure, and the SHAPE conversion factor (slope of the linear fit) was determined. In doing so, a specific signal processing technique (based on a small temporal window) was used to account for time-decay of MB subharmonic signal during a simulated CMG. RESULTS: A strong inverse linear relationship was found to exist between SHAPE and bladder phantom pressures for each of the CMG filling and post-filling events ( r2> 0.9, root mean square error < 0.3 dB, standard error <0.01 dB, and P < 0.001). SHAPE showed a transient behavior in measuring bladder phantom pressure. The SHAPE conversion factor (in dB/cm H 2 O) varied between filling and post-filling events, as well as by post-filling time. The magnitude of the SHAPE conversion factor tended to increase immediately after filling and then decreases with time. CONCLUSIONS: Microbubble subharmonic emission is an excellent indicator of bladder phantom pressure variation. The strong correlation between SHAPE signal and bladder phantom pressure is indicative of the applicability of this method in measuring bladder pressure during a CMG. Our results suggest that different SHAPE conversion factors may be needed for different events during a CMG (ie, at different time points of a CMG). These findings will help us better protocolize this method for introduction into human subjects and allow us to take the next step toward developing a catheter-free voiding CMG using SHAPE.

"I have to be a man for my son": The narrative uses of fatherhood in prison.

Research on incarcerated fathers tends to accentuate the harmful familial consequences of parental incarceration and discuss how having children might prompt incarcerated fathers to desist from crime. Less attention has focused on how narratives of fatherhood shape the day-to-day dynamics of incarceration. Drawing on 93 qualitative interviews with incarcerated fathers in Western Canada, we focus specifically on our participants' parenting narratives. Such narratives are significant interventions in the world, allowing incarcerated fathers to frame their identities in particular ways while simultaneously shaping personal behaviour. Our research, 1. Identifies important fatherhood narratives provided by our participants, and 2. Details how such narratives operate in prison, allowing our participants to advance personal agendas that are themselves related to the dynamics of incarceration. In doing so, we provide insights into incarcerated fathers' situations and advance criminological efforts to appreciate how different actors entangled in the criminal justice system conceive, manage, and narrate their situation.

Ultrasound Contrast Stability for Urinary Bladder Pressure Measurement.

The goal of this study was to evaluate ultrasound contrast microbubbles (MB) stability during a typical cystometrogram (CMG) for bladder pressure measurement application using the subharmonic-aided pressure estimation technique. A detailed study of MB stability was required given two unique characteristics of this application: first, bulk infusion of MBs into the bladder through the CMG infusion system, and second, duration of a typical CMG which may last up to 30 min. To do so, a series of size measurement and contrast-enhanced ultrasound imaging studies under different conditions were performed and the effects of variables that we hypothesized have an effect on MB stability, namely, i) IV bag air headspace, ii) MB dilution factor, and iii) CMG infusion system were investigated. The results verified that air volume in intravenous (IV) bag headspace was not enough to have a significant effect on MB stability during a CMG. We also showed that higher MB dosage results in a more stable condition. Finally, the results indicated that the CMG infusion system adversely affects MB stability. In summary, to ensure MB stability during the entire duration of a CMG, lower filling rates (limited by estimated bladder capacity in clinical applications) and/or higher MB dosage (limited by FDA regulations and shadowing artifact) and/or the consideration of alternative catheter design may be needed.

Transparency practices at the FDA: A barrier to global health.

Data sharing among regulators must be "business as usual".

Hydroxycarbamide treatment reduces transcranial Doppler velocity in the absence of transfusion support in children with sickle cell anaemia, elevated transcranial Doppler velocity, and cerebral vasculopathy: the EXTEND trial.

EXpanding Treatment for Existing Neurological Disease (EXTEND) investigated whether hydroxycarbamide lowers transcranial Doppler (TCD) velocities in Jamaican children with sickle cell anaemia (SCA) and elevated TCD velocity with or without previous stroke. Forty-three children (age 2-17 years) with baseline maximum time-averaged mean velocity (TAMV) ≥ 170 cm/s were stratified into three risk categories based on treatment status and stroke history: Group 1 (no history of stroke, on hydroxycarbamide, n = 12); and Groups 2 (no stroke, no hydroxycarbamide, n = 21) and 3 (previous stroke, no hydroxycarbamide, n = 10). Open-label hydroxycarbamide at 20 mg/kg/day was commenced, with escalation to maximum tolerated dose (MTD) based on mild marrow suppression (average dose 25·4 ± 4·5 mg/kg/day). TCD was performed every six months with brain magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) at baseline and after 18-months of hydroxycarbamide. The maximum TAMV decreased significantly compared to baseline (24 ± 30 cm/s, P < 0·0001), with similar declines in all groups. Clinical stroke occurred in five children, one in Group 1, none in Group 2, and four in Group 3, P = 0·0032, comparing group incidence rates. Brain MRI/MRA was stable in children without clinical stroke. EXTEND documents the feasibility and benefits of hydroxycarbamide at MTD to lower TCD velocities and reduce stroke risk in children with SCA and no history of primary stroke in low-resource settings without transfusion management.

The 5:1 rule overestimates the needed tunnel length during ureteral reimplantation.

AIMS: Paquin asserts that in order for ureterovesical junctions (UVJs) to prevent reflux, the ureteral tunnel length-to-diameter ratio needs to be 5:1. We hypothesize that the surgical implementation of this observation results in an overestimation of the needed length-to-diameter ratio to prevent vesicoureteral reflux. METHODS: With finite elements, we model the urine storage phase of the bladder under nonlinear conditions. In the reference state, the bladder is assumed to be a sphere with an oblique straight elliptical hole as the UVJ. Broad parametric studies on different length-to-diameter ratios are performed as the bladder volume increases from 10% to 110% capacity. RESULTS: The capability of the UVJ to prevent reflux during storage depends on its length-to-diameter ratio. UVJs with larger length-to-diameter ratios lengthen and narrow as the bladder volume increases, causing the closure of the UVJ and rise in its flow resistance. Our model shows that the UVJ length-to-diameter ratio decreases as the bladder volume increases. The 5:1 ratio implemented at 80% capacity-approximate volume or bladder wall stretch during ureteroneocystostomy (UNC)-corresponds to 7:1 at the reference state-used by Paquin. The 5:1 ratio implemented at the reference state corresponds to 3:1 at 80% capacity. CONCLUSIONS: Our modeling results are consistent with Paquin's original observation on the significance of the UVJ length-to-diameter ratio in preventing reflux. They, however, indicate that the surgical implementation of this rule during UNC results in an overestimation of the requisite tunnel length-to-diameter ratio to prevent reflux. They also suggest that the UVJ closure is due to the bladder wall deformation rather than the pressure.

Ureterovesical junction deformation during urine storage in the bladder and the effect on vesicoureteral reflux.

The motivation behind this study is to understand how ureterovesical junction (UVJ) deformation during urine storage in the bladder affects vesicoureteral reflux (VUR), when urine flows backward from the bladder toward the kidneys. Using nonlinear, large deformation finite element simulations, the deformation of the bladder wall during urine storage is modeled in this study. The bladder wall is assumed to be a homogeneous, isotropic, hyperelastic spherical shell with a finite thickness. The UVJ is defined as a straight elliptical cylindrical hole through the bladder wall at the reference configuration before inflation. Broad parametric studies on different UVJ configurations are performed as the bladder inner surface stretches by a factor of 2.2 from an initial radius corresponding to bladder volumes of 10% to slightly over physiologic capacity. For each considered UVJ configuration, a simple fluid analysis of the tunnel flow resistance compares different bladder inner surface stretch ratios. Our model shows that the deformation of the UVJ depends on its orientation with respect to the bladder wall radial and circumferential directions. We show that as the UVJ insertion angle increases, the UVJ cross section decreases and its tunnel length increases during urine storage causing the closure of the UVJ and a rise in its flow resistance. The modeling results indicate that UVJ closure could be explained by bladder wall deformation rather than the local differential pressure. Our findings are consistent with the accepted primary anti-reflux mechanism of the UVJ being dependent on the tunnel length-to-diameter ratio and consequently the UVJ insertion angle.

Marital status and outcomes in patients with cardiovascular disease.

The national burden of cardiovascular disease (CVD) continues to impose significant risk of morbidity, mortality and increased costs. While traditional risk factors have been well-established, the evolving role of non-traditional risk factors, including socioeconomic and psychosocial factors, is increasingly being recognized. Several studies have acknowledged an association between marital status and the presence of CVD and its associated adverse outcomes. Across multiple U.S. and international cohorts, patients who are unmarried, including those who are divorced, separated, widowed, or never married, have an increased rate of adverse cardiovascular events when compared to their married counterparts. Some studies suggest that marriage may have a more protective role for men compared to women. Furthermore, dissatisfaction in a marriage and marriage quality have significant impact on cardiovascular risk. Psychosocial and socioeconomic factors, as well as other acute stressors, may contribute to the association between marital status and CVD outcomes, but the underlying mechanisms are not completely clear. Further investigation is required to identify potential targets for intervention and to determine whether more aggressive targeting of standard anti-atherosclerotic therapies can favorably impact CVD risk in unmarried patients.

Enhanced Selection of Candidates for Same-Day and Outpatient Total Knee Arthroplasty.

BACKGROUND: Medicare removed total knee arthroplasty (TKA) from its inpatient-only list and private insurers created ambulatory surgical codes; these changes bring about logistical challenges for TKA episode planning. We identified preoperatively determined factors associated with hospital length of stay for (1) same-day discharge (SDD) and (2) inpatient TKA defined by Medicare's 2-midnight rule benchmark. METHODS: We retrospectively reviewed 325 consecutive unilateral primary TKAs performed on patients completing the Perioperative Surgical Home preoperative optimization pathway within a single hospital system. Stepwise logistic regression modeling was performed to identify preoperatively determined factors associated with (1) SDD and (2) inpatient TKA. We compared these models' ability to discern the length of stay category to the Risk Assessment and Prediction Tool (RAPT) score alone. RESULTS: The cohort included 32 (10%) SDD, 189 (58%) next-day discharges, and 104 (32%) inpatients. Lower body mass index (BMI; odds ratio [OR], 0.92; 95% CI, 0.85-0.1.0; P = .04) and fewer self-reported allergies (OR, 0.66; 95% CI, 0.46-0.95; P = .03) were associated with SDD. The SDD model outperformed the RAPT alone (C-statistic, 0.73 vs 0.52; P < .01). Older age (OR, 0.96; P = .04), higher BMI (OR, 0.93; P 0.01), lower RAPT score (OR, 1.2; P = .04), and later surgery start time (OR, 0.80; P < .01) were associated with inpatient discharge. The inpatient model outperformed the RAPT alone (C-statistic, 0.74 vs 0.62; P < .01). CONCLUSION: We identified preoperatively determined factors associated with (1) SDD as BMI and allergies and (2) inpatient TKA as age, BMI, RAPT score, and surgery start time. Hospitals, providers, patients, families, and payers can use this information for TKA episode planning.

Socioeconomic Status and Cardiovascular Outcomes: Challenges and Interventions.

Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD). Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors. In addition, disparities based on sex have been shown in several studies. Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors. Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes. Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs. Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas. Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging. Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk. We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment.

Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03).

PURPOSE: Aromatase inhibitors are the most commonly prescribed adjuvant endocrine therapy for hormone-dependent early breast cancer in postmenopausal women. Among Canadian Cancer Trials Group MA.27 participants, anastrozole and exemestane had comparable 5-year event-free survival. This companion study examined differences in patient-reported treatment-related symptoms (TRS) and health-related quality of life (HRQL) among postmenopausal women randomized to anastrozole or exemestane. METHODS: MA.27 participants (N = 686, of 7576) randomized to 5 years of anastrozole (1 mg/day, n = 371, Arm A) or exemestane (25 mg/day, n = 315, Arm E) completed the 56-item Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) questionnaire to assess TRS and HRQL. The FACT-ES was completed at baseline, 3, 6, 12, and 24 months. RESULTS: No significant differences in FACT-ES median scores measuring TRS and HRQL were observed between treatment arms at any time point. Change in TRS from baseline was statistically significant at 3, 6, 12, and 24 months. HRQL was stable over time in both arms. Greater TRS burden was associated with poorer HRQL (coefficient = 0.57, p < 0.001). Twenty percent of patients discontinued AI therapy by month 24 and 32% discontinued AIs at 4 years. In both arms, patients reporting more side effect bother prior to initiating study treatment had a higher risk of discontinuing treatment before completing protocol therapy (hazard ratio [HR] 1.29, 95% CI 1.08-1.55, p = 0.01). CONCLUSIONS: TRS and HRQL were comparable between anastrozole and exemestane. TRS negatively affect HRQL. Women who report being bothered by treatment side effects prior to initiating an AI are at increased risk for early treatment discontinuation.

Natural Approaches in Diabetes Management: A Review of Diet, Exercise, and Natural Products.

Diabetes mellitus (DM) is a highly prevalent condition that causes significant morbidity and mortality in the United States and worldwide. Conventional therapies include lifestyle modification, oral pharmacological agents, and subcutaneous insulin. Emerging data suggest that natural approaches to the treatment of DM may help supplement current therapies for further glycemic control. Herein, we review the evidence of several natural modalities for DM treatment. We describe the pathophysiology of diabetes and its complications, provide an overview of current pharmacologic treatments, and finally, discuss natural approaches to diabetes management. Specifically, we will describe on the utility of diet, physical activity, and common natural products in the treatment of DM and focus on recent, high-quality studies. Adverse effects and potential interactions of each therapy will be highlighted where applicable.

Marital Status and Outcomes in Patients With Cardiovascular Disease.

BACKGROUND: Being unmarried is associated with decreased survival in the general population. Whether married, divorced, separated, widowed, or never-married status affects outcomes in patients with cardiovascular disease has not been well characterized. METHODS AND RESULTS: A prospective cohort (inception period 2003-2015) of 6051 patients (mean age 63 years, 64% male, 23% black) undergoing cardiac catheterization for suspected or confirmed coronary artery disease was followed for a median of 3.7 years (interquartile range: 1.7-6.7 years). Marital status was stratified as married (n=4088) versus unmarried (n=1963), which included those who were never married (n=451), divorced or separated (n=842), or widowed (n=670). The relationship between marital status and primary outcome of cardiovascular death and myocardial infarction was examined using Cox regression models adjusted for clinical characteristics. There were 1085 (18%) deaths from all causes, 688 (11%) cardiovascular-related deaths, and 272 (4.5%) incident myocardial infarction events. Compared with married participants, being unmarried was associated with higher risk of all-cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI], 1.06-1.47), cardiovascular death (HR: 1.45; 95% CI, 1.18-1.78), and cardiovascular death or myocardial infarction (HR: 1.52; 95% CI, 1.27-1.83). Compared with married participants, the increase in cardiovascular death or myocardial infarction was similar for the participants who were divorced or separated (HR: 1.41; 95% CI, 1.10-1.81), widowed (HR: 1.71; 95% CI, 1.32-2.20), or never married (HR: 1.40; 95% CI, 0.97-2.03). The findings persisted after adjustment for medications and other socioeconomic factors. CONCLUSIONS: Marital status is independently associated with cardiovascular outcomes in patients with or at high risk of cardiovascular disease, with higher mortality in the unmarried population. The mechanisms responsible for this increased risk require further study.

Psychobiography: Theory and method.

Psychobiography is best understood as a branch of applied personality science in which experimental findings are used to explore the lives and personalities of public figures, from artists to politicians. This article introduces the field, addresses questions commonly raised about it, and explores, among other subjects, what psychobiographical research might offer to the field of psychology. Two recent model psychobiographies are described in detail-McAdams's (2010) profile of George W. Bush and Kasser's (2013) analysis of John Lennon-both of which are oriented scientifically and rooted in experimentally derived concepts. Lastly, criteria for evaluating psychobiographical studies are summarized, as well as attributes of effective psychobiography that tend to include the components of fact, fit, and function. (PsycINFO Database Record

Cardiovascular disease risk reduction in diabetes through conventional and natural approaches.

Type 2 diabetes mellitus (DM) is a significant cause of premature complications and mortality in patients with cardiovascular disease (CVD). In addition to lifestyle modifications, conventional treatment of DM consists of oral hypoglycemic agents, insulin sensitizers, and subcutaneous insulin. In diabetic individuals with or at risk for CVD, aspirin and statin therapy reduce CVD morbidity and mortality. Several natural or herbal supplements have shown potential benefit in patients with CVD and DM. We provide an overview of the current guidelines for treatment of DM and CVD. We then review the literature to describe the efficacy of natural approaches to CVD risk reduction in diabetic patients, with a focus on physical activity, dietary modification, and natural/herbal supplements. Activity and diet improve cardiovascular outcomes in patients with CVD and DM. Natural and herbal supplements have potential for benefit but require further research to determine their efficacy and safety.

Comprehensive Cardiovascular Risk Reduction and Cardiac Rehabilitation in Diabetes and the Metabolic Syndrome.

The epidemic of obesity has contributed to a growing burden of metabolic syndrome (MetS) and diabetes mellitus (DM) worldwide. MetS is defined as central obesity along with associated factors such as hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, and hypertension. MetS and DM are associated with significant cardiovascular morbidity and mortality. Healthy behavioural modification is the cornerstone for reducing the atherosclerotic cardiovascular disease burden in this population. Comprehensive, multidisciplinary cardiac rehabilitation (CR) programs reduce mortality and hospitalizations in patients with MetS and DM. Despite this benefit, patients with MetS and DM are less likely to attend and complete CR because of numerous barriers. Implementation of innovative CR delivery models might improve utilization of CR and cardiovascular outcomes in this high-risk population.