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Objective: We evaluated the efficacy of risk-based, protocol-driven management versus (vs) usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSC) ., Summary Background Data: Major cancer surgery is associated with significant perioperative risks which result in worse long-term outcomes., Methods: Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and co-management vs usual management. The primary study outcome was 30-day rate of DSC. Additional outcomes included complications, adverse events, health care utilization, health-related quality of life (HRQOL), and disease-free and overall survival (DFS and OS)., Results: Between August 2014 and June 2020, 1529 patients were enrolled and randomly allocated to the study arms; 738 patients in the Intervention Arm and 732 patients in the Control Arm were eligible for analysis. 30-day rate of DSC with the intervention was 15.0% (95% CI, 12.5-17.6%) vs 14.1%, (95% CI, 11.6-16.6%) with usual management (P=0.65). There were no differences in 30-day rates of complications or adverse events (including return to the operating room); postoperative length of stay; rate of discharge to home; or 30, 60, or 90-day HRQOL or rates of hospital readmission or receipt of anti-neoplastic therapy between the study arms. At median follow-up of 48 months, OS (P=0.57) and DFS (P=0.91) were similar., Conclusions: Risk-based, protocol-driven management did not reduce 30-day rate of DSC after elective major cancer surgery compared to usual management, nor improve postoperative health care utilization, HRQOL, or cancer outcomes. Trials are needed to identify cost-effective, tailored perioperative strategies to optimize outcomes after major cancer surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Stroke is a second leading cause of death globally, with an estimated one in four adults suffering a stroke in their lifetime. We aimed to describe the clinical characteristics, quality of care, and outcomes in adults with stroke in urban Northwestern Tanzania., Methods: We analyzed de-identified data from a prospective stroke registry from Bugando Medical Centre in Mwanza, the second largest city in Tanzania, between March 2020 and October 2022. This registry included all adults ⩾18 years admitted to our hospital who met the World Health Organization clinical definition of stroke. Information collected included demographics, risk factors, stroke severity using the National Institutes of Health Stroke Scale, brain imaging, indicators for quality of care, discharge modified Rankin Scale, and in-hospital mortality. We examined independent factors associated with mortality using logistic regression., Results: The cohort included 566 adults, of which 52% (294) were female with a mean age of 65 ± 15 years. The majority had a first-ever stroke 88% (498). Premorbid hypertension was present in 86% (488) but only 41% (200) were taking antihypertensive medications before hospital admission; 6% (32) had HIV infection. Ischemic strokes accounted for 66% (371) but only 6% (22) arriving within 4.5 h of symptom onset. In-hospital mortality was 29% (127). Independent factors associated with mortality were severe stroke (adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI) = 1.47-2.24, p < 0.001), moderate to severe stroke (aOR = 1.49, 95% CI = 1.22-1.84, p < 0.001), moderate stroke (aOR = 1.80, 95% CI = 1.52-2.14, p < 0.001), leukocytosis (aOR = 1.19, 95% CI = 1.03-1.38, p = 0.022), lack of health insurance coverage (aOR = 1.15, 95% CI = 1.02-1.29, p = 0.025), and not receiving any form of venous thromboembolism prophylaxis (aOR = 1.18, 95% CI = 1.02-1.37, p = 0.027)., Conclusion: We report a stroke cohort with poor in-hospital outcomes in urban Northwestern Tanzania. Early diagnosis and treatment of hypertension could prevent stroke in this region. More work is needed to raise awareness about stroke symptoms and to ensure that people with stroke receive guidelines-directed therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: Thresholds for abnormal transcranial Doppler cerebrovascular reactivity (CVR) studies are poorly understood, especially for patients with cerebrovascular disease. Using a real-world cohort with cerebral arterial stenosis, we sought to describe a clinically significant threshold for carbon dioxide reactivity (CO2R) and vasomotor range (VMR)., Methods: CVR studies were performed during conditions of breathing room air normally, breathing 8% carbon dioxide air mixture, and hyperventilation. The mean and standard deviation (SD) of CO2R and VMR were calculated for the unaffected side in patients with unilateral stenosis; a deviation of 2 SDs below the mean was chosen as the threshold for abnormal. Receiver operating characteristic (ROC) curves for both sides for patients with unilateral and bilateral stenosis were evaluated for sensitivity (Sn) and specificity (Sp)., Results: A total of 133 consecutive CVR studies were performed on 62 patients with stenosis with mean±SD age 55±16 years. Comorbidities included hypertension (60%), diabetes (15%), stroke (40%), and smoking (35%). In patients with unilateral stenosis, mean±SD CO2R for the unaffected side was 1.86±0.53%, defining abnormal CO2R as <0.80%. Mean±SD CO2R for the affected side was 1.27±0.90%. The CO2R threshold predicted abnormal acetazolamide single-photon emission computed tomography (SPECT) (Sn = .73, Sp = .79), CT/MRI perfusion abnormality (Sn = .42, Sp = .77), infarction on MRI (Sn = .45, Sp = .76), and pressure-dependent exam (Sn = .50, Sp = .76). For the unaffected side, mean±SD VMR was 39.5±15.8%, defining abnormal VMR as <7.9%. For the affected side, mean±SD VMR was 26.5±17.8%. The VMR threshold predicted abnormal acetazolamide SPECT (Sn = .46, Sp = .94), infarction on MRI (Sn = .27, Sp = .94), and pressure-dependent exam (Sn = .31, Sp = .90)., Conclusions: In patients with multiple vascular risk factors, a reasonable threshold for clinically significant abnormal CO2R is <0.80% and VMR is <7.9%. Noninvasive CVR may aid in diagnosing and risk stratifying patients with stenosis., (© 2024 American Society of Neuroimaging.)

A modified version of the PGDx elio TM Plasma Resolve assay was validated as a laboratory-developed test (LDT) for clinical use in the Molecular Diagnostics Laboratory at Fox Chase Cancer Center. The test detects single nucleotide variants (SNVs) and small insertions and deletions (indels) in 33 target genes using fragmented genomic DNA extracted from plasma. The analytical performance of this assay was assessed with reference standard DNA and 29 samples from cancer patients and detected 66 SNVs and 23 indels. Using 50 ng of input DNA, the sensitivity was 95.5% to detect SNVs at 0.5% allele frequency, and the specificity was 92.3%. The sensitivity to detect indels at 1% allele frequency was 70.4%. A cutoff of 0.25% variant allele frequency (VAF) was set up for diagnostic reporting. An inter-laboratory study of concordance with an orthologous test resulted in a positive percent agreement (PPA) of 91.7%.

To decarbonize our global energy system, sustainably harvesting metals from diverse sourcewaters is essential. Membrane-based processes have recently shown great promise in meeting these needs by achieving high metal ion selectivities with relatively low water and energy use. An example is nanofiltration, which harnesses steric, dielectric, and Donnan exclusion mechanisms to perform size- and charge-based fractionation of metal ions. To further optimize nanofiltration systems, multicomponent models are needed; however, conventional methods necessitate large amounts of data for model calibration, introduce substantial uncertainty into the characterization process, and often yield poor results when extrapolated. In this work, we develop a new computational architecture to alleviate these concerns. Specifically, we develop a framework that: (1) reduces the data requirement for model calibration to only charged species measurements; (2) eliminates uncertainty propagation problems present in conventional characterization processes; (3) enables exploration of pH optimization for enhancing metal ion selectivities; and (4) enables uncertainty quantification to assess the sensitivity of partition coefficients and ion driving forces to learned pore size distributions. Our framework captures eight independent datasets comprising over 500 measurements to within ±15%. Our studies also suggest that the expectation-maximization algorithm can effectively learn pore size distributions and that optimizing pH can improve metal ion selectivities by a factor of 3-10×. Our findings also reveal that image charges appear to play a less pronounced role in dielectric exclusion under the studied conditions and that ion driving forces are more sensitive to pore size distributions than partition coefficients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Stroke is the second leading cause of death worldwide, with the highest mortality rates in low- to middle-income countries, particularly in sub-Saharan Africa. We aimed to investigate the predictors of 30-day mortality among patients with stroke admitted at a tertiary teaching hospital in Northwestern Tanzania., Methods: This cohort study recruited patients with the World Health Organization's clinical definition of stroke. Data were collected on baseline characteristics, the degree of neurological impairment at admission (measured using the National Institutes of Health Stroke Scale), imaging and electrocardiogram (ECG) findings, and post-stroke complications. The modified Rankin scale (mRS) was used to assess stroke outcomes. Kaplan-Meier analysis was used to describe survival, and the Cox proportional hazards model was used to examine predictors of mortality., Results: A total of 135 patients were enrolled, with a mean age of 64.5 years. Hypertension was observed in 76%, and 20% were on regular anti-hypertensive medications. The overall 30-day mortality rate was 37%. Comparing patients with hemorrhagic and ischemic stroke, 25% had died by day 5 [25th percentile survival time (in days): 5 (95% CI: 2-14)] versus day 23 [25th percentile survival time (in days): 23 (95% CI: 11-30) (log-rank p < 0.001)], respectively. Aspiration pneumonia was the most common medical complication, occurring in 41.3% of patients. ECG abnormalities were observed in 54.6 and 46.9% of patients with hemorrhagic and ischemic stroke, respectively. The most common patterns were as follows: ST changes 29.6 vs. 30.9%, T-wave inversion 34.1 vs. 38.3%, and U-waves 18.2 vs. 1.2% in hemorrhagic and ischemic stroke, respectively. Independent predictors for case mortality were as follows: mRS score at presentation (4-5) [aHR 5.50 (95% CI: 2.02-15.04)], aspiration pneumonia [aHR 3.69 (95% CI: 1.71-13.69)], ECG abnormalities [aHR 2.28 (95% CI: 1.86-5.86)], and baseline stroke severity [aHR 1.09 (95% CI: 1.02-1.17)]., Conclusion: Stroke is associated with a high 30-day mortality rate in Northwestern Tanzania. Concerted efforts are warranted in managing patients with stroke, with particular attention to individuals with severe strokes, ECG abnormalities, and swallowing difficulties to reduce early morbidity and mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Matuja, Mlay, Kalokola, Ngoya, Shindika, Andrew, Ngimbwa, Ahmed, Tumaini, Khanbhai, Mutagaywa, Manji, Sheriff and Mahawish.)

Background: Large vessel ischemic strokes account for more than one-third of all strokes associated with substantial morbidity and mortality without early intervention. The incidence of large vessel occlusion (LVO) is not known in sub-Saharan Africa (SSA). Definitive vessel imaging is not routinely available in resource-limited settings., Aims: We aimed to investigate the burden and outcomes of presumed LVO among patients with ischemic stroke admitted to a large tertiary academic hospital in Tanzania., Methods: This cohort study recruited all consenting first-ever ischemic stroke participants admitted at a tertiary hospital in Tanzania. Demographic data were recorded, and participants were followed up to 1 year using the modified Rankin Scale (mRS). A diagnosis of presumed LVO was made by a diagnostic neuroradiologist and interventional neurologist based on contiguous ischemic changes in a pattern consistent with proximal LVO on a non-contrast computed tomography head. We examined factors associated with presumed LVO using logistic regression analysis. Inter-observer Kappa was calculated., Results: We enrolled 158 first-ever ischemic strokes over 8 months with a mean age of 59.7 years. Presumed LVO accounted for 39.2% [95% confidence interval (CI) 31.6-47.3%] and an overall meantime from the onset of stroke symptoms to hospital arrival was 1.74 days. Participants with presumed LVO were more likely to involve the middle cerebral artery (MCA) territory (70.9%), p < 0.0001. Independent factors on multivariate analysis associated with presumed LVO were hypertension [adjusted odds ratio (aOR) 5. 74 (95% CI: 1.74-18.9)] and increased waist-hip ratio [aOR 7.20 (95% CI: 1.83-28.2)]. One-year mortality in presumed LVO was 80% when compared with 73.1% in participants without presumed LVO. The Cohen's Kappa inter-observer reliability between the diagnostic neuroradiologist and interventional neurologist was 0.847., Conclusion: There is a high burden of presumed LVO associated with high rates of 1-year morbidity and mortality at a tertiary academic hospital in Tanzania. Efforts are needed to confirm these findings with definitive vessel imaging, promoting cost-effective preventive strategies to reduce the burden of non-communicable diseases (NCDs), and a call for adopting endovascular therapies to reduce morbidity and mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Matuja, Ahmed, Munseri, Khanbhai, Tessua, Lyimo, Rodriguez, Gupta, Maud, Chaudhury, Manji and Sheriff.)

Objective: Pediatric asthma emergency department (ED) visits and repeat visits place a substantial burden on healthcare. National and provincial level studies demonstrate geographic variation in asthma ED visits and links to marginalization, but preclude translation into practical targeting of healthcare delivery. It is important to understand the relationship between pediatric asthma ED visits and marginalization at a more granular level. To map the city-level geographic variation in pediatric asthma ED visit and re-visit rates at the Children's Hospital of Eastern Ontario (CHEO) in Ottawa, Canada and the relationship with marginalization., Methods: We performed a single center retrospective cohort study of children ages 1-17 with one or more ED visits for asthma at the CHEO in Ottawa. Using postal codes, we linked patients to census tracts. Per census tract, we mapped pediatric asthma ED visit and re-visit rates within one year and identified overlap with the Ontario Marginalization Index., Results: Of 1,620 children with an index ED visit, 18.5% had a repeat ED visit. We identified 10 hot spot census tracts each for pediatric asthma ED visit and re-visit rates. We identified an overlap between urban hot spots and areas with high ethnic concentration or low dependency., Conclusion: At a granular, city-wide level, pediatric asthma ED visit and re-visit rates are heterogeneous. Urban hot spots, in contrast to rural, have more overlap with marginalization, especially ethnic concentration. These methods can be used in other jurisdictions to inform practical community strategies for geographically-targeted prevention of pediatric asthma-related ED visits in vulnerable areas.Abbreviations:ED:Emergency department;CHEO:Children's Hospital of Eastern Ontario;PRAM:Pediatric Respiratory Assessment Measure;ON-Marg:Ontario Marginalization Index;SES:Socioeconomic status;US:United States., Supplemental data for this article can be accessed at publisher's website.

Introduction Endovascular therapy (EVT) use increased following clinical trials publication in 2015, but limited data suggest there may be persistent race and ethnicity differences. Methods and Results We included all patients with acute ischemic stroke arriving within 6 hours of last known well and with National Institute of Health Stroke Scale (NIHSS) score ≥6 between April 2012 and June 2019 in the Get With The Guidelines-Stroke database and evaluated the association between race and ethnicity and EVT use and outcomes, comparing the era before versus after 2015. Of 302 965 potentially eligible patients; 42 422 (14%) underwent EVT. Although EVT use increased over time in all racial and ethnic groups, Black patients had reduced odds of EVT use compared with non-Hispanic White (NHW) patients (adjusted odds ratio [aOR] before 2015, 0.68 [0.58‒0.78]; aOR after 2015, 0.83 [0.76‒0.90]). In-hospital mortality/discharge to hospice was less frequent in Black, Hispanic, and Asian patients compared with NHW. Conversely discharge home was more frequent in Hispanic (29.7%; aOR, 1.28 [1.16‒1.42]), Asian (28.2%; aOR, 1.23 [1.05‒1.44]), and Black (29.1%; aOR, 1.08 [1.00‒1.18]) patients compared with NHW (24%). However, at 3 months, functional independence (modified Rankin Scale, 0-2) occurred less frequently in Black (37.5%; aOR, 0.84 [0.75‒0.95]) and Asian (33%; aOR, 0.79 [0.65‒0.98]) patients compared with NHW patients (38.1%). Conclusions In a large cohort of patients treated with EVT, Black versus NHW patient disparities in EVT use have narrowed over time but still exist. Discharge related outcomes were slightly more favorable in racial and ethnic underrepresented groups; 3-month functional outcomes were worse but improved across all groups with time.

Background: Venous stenting (VS) for venous sinus stenosis in the setting of idiopathic intracranial hypertension has been increasing in acceptance by neurointerventionalists. Stent-adjacent stenosis (SAS) and in-stent stenosis leading to symptom recurrence and the need for retreatment are known delayed complications. However, the effect of the dual antiplatelet therapy (DAPT) duration on these complications has remained poorly characterized., Methods: An extensive literature search was performed to identify reports of VS for patients with idiopathic intracranial hypertension from 2000 to 2020. The primary outcome was the occurrence of SAS. The secondary outcomes included the occurrence of composite stenosis (in-stent stenosis and SAS) and stent survival, defined as the need for retreatment or other surgical management. Generalized linear mixed models were used to explore the effects of DAPT duration (3 vs ≥6 months) on the primary and secondary outcomes., Results: A total of 325 patients met the inclusion criteria and were included in our analysis. SAS occurred in 9% (95% confidence interval, 6%-15%) of the patients, and stent survival was 90% (95% confidence interval, 84%-93%) in the cohort. With every 1-mm Hg increase in the venous pressure gradient, an 8% decrease was found in the odds of stent survival (P = 0.043). The meta-regression revealed no association between the DAPT duration and the primary outcome or the odds of composite stenosis and stent survival., Conclusions: We found no differences between 3 and ≥6 months of DAPT in terms of the risk of stent stenosis or stent survival. However, patients with a higher venous pressure gradient before VS had a greater risk of stent failure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The transfemoral approach (TFA) has been the traditional approach for neurointerventional cases. While the TFA allows for triaxial support in flow diverting stent cases, it is associated with access site complications. Recently, the transradial approach (TRA) has emerged as a safer alternative to the TFA. To the best of our knowledge, there have only been single-center studies comparing outcomes in flow diverter cases for these approaches. We demonstrate the safety and feasibility of the TRA for placement of flow diverting stents in the treatment of unruptured intracranial aneurysms at two high-volume centers., Materials and Methods: We performed a retrospective review of prospectively collected institutional databases at two high-volume neuroendovascular centers. Cases from 2016 to 2018 of unruptured intracranial aneurysms treated by flow diverting stenting accessed through either the TRA or the TFA were compared. Patient demographics, procedural and radiographic metrics including location and size of the aneurysm, size, and length of the flow diverter implant, and fluoroscopic time were recorded. Puncture site complications and length of hospital stay were also included in the data analysis., Results: There were three out of 29 TRA cases which were converted to the TFA. None of the TRA patients experienced site complications, whereas three TFA patients experienced site complications. While TRA and TFA patients did not differ significantly in their exposure to radiation, TRA patients experienced shorter hospital stays., Conclusions: While long-term studies are still lacking regarding this approach, we demonstrate that the TRA is a safe and feasible approach for flow diverter stent placement., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Brain Circulation.)

Purpose of Review: In this review article we will discuss the acute hypertensive response in the context of acute ischemic stroke and present the latest evidence-based concepts of the significance and management of the hemodynamic response in acute ischemic stroke., Recent Findings: Acute hypertensive response is considered a common hemodynamic physiologic response in the early setting of an acute ischemic stroke. The significance of the acute hypertensive response is not entirely well understood. However, in certain types of acute ischemic strokes, the systemic elevation of the blood pressure helps to maintain the collateral blood flow in the penumbral ischemic tissue. The magnitude of the elevation of the systemic blood pressure that contributes to the maintenance of the collateral flow is not well established. The overcorrection of this physiologic hemodynamic response before an effective vessel recanalization takes place can carry a negative impact in the final clinical outcome. The significance of the persistence of the acute hypertensive response after an effective vessel recanalization is poorly understood, and it may negatively affect the final outcome due to reperfusion injury. Acute hypertensive response is considered a common hemodynamic reaction of the cardiovascular system in the context of an acute ischemic stroke. The reaction is particularly common in acute brain embolic occlusion of large intracranial vessels. Its early management before, during, and immediately after arterial reperfusion has a repercussion in the final fate of the ischemic tissue and the clinical outcome.

Significance: Intracranial pressure (ICP), variability in perfusion, and resulting ischemia are leading causes of secondary brain injury in patients treated in the neurointensive care unit. Continuous, accurate monitoring of cerebral blood flow (CBF) and ICP guide intervention and ultimately reduce morbidity and mortality. Currently, only invasive tools are used to monitor patients at high risk for intracranial hypertension., Aim: Diffuse correlation spectroscopy (DCS), a noninvasive near-infrared optical technique, is emerging as a possible method for continuous monitoring of CBF and critical closing pressure (CrCP or zero-flow pressure), a parameter directly related to ICP., Approach: We optimized DCS hardware and algorithms for the quantification of CrCP. Toward its clinical translation, we validated the DCS estimates of cerebral blood flow index (CBFi) and CrCP in ischemic stroke patients with respect to simultaneously acquired transcranial Doppler ultrasound (TCD) cerebral blood flow velocity (CBFV) and CrCP., Results: We found CrCP derived from DCS and TCD were highly linearly correlated (ipsilateral R2  =  0.77, p  =  9  ×  10  -  7; contralateral R2  =  0.83, p  =  7  ×  10  -  8). We found weaker correlations between CBFi and CBFV (ipsilateral R2  =  0.25, p  =  0.03; contralateral R2  =  0.48, p  =  1  ×  10  -  3) probably due to the different vasculature measured., Conclusion: Our results suggest DCS is a valid alternative to TCD for continuous monitoring of CrCP.

It would be useful for researchers, practitioners, and decision-makers to anticipate the hazards that workers will face in the future. The focus of this study is a systematic review of published information to identify and characterize scenarios and hazards in the future of work. Eleven bibliographic databases were systematically searched for papers and reports published from 1999 to 2019 that described future of work scenarios or identified future work-related hazards. To compile a comprehensive collection of views of the future, supplemental and ad hoc searches were also performed. After screening all search records against a set of predetermined criteria, the review yielded 36 references (17 peer-reviewed, 4 gray, and 15 supplemental) containing scenarios. In these, the future of work was described along multiple conceptual axes (e.g. labor market changes, societal values, and manual versus cognitive work). Technology was identified as the primary driver of the future of work in most scenarios, and there were divergent views in the literature as to whether technology will create more or fewer jobs than it displaces. Workforce demographics, globalization, climate change, economic conditions, and urbanization were also mentioned as influential factors. Other important themes included human enhancement, social isolation, loneliness, worker monitoring, advanced manufacturing, hazardous exposures, sustainability, biotechnology, and synthetic biology. Pandemics have not been widely considered in the future of work literature, but the recent COVID-19 pandemic illustrates that was short-sighted. Pandemics may accelerate future of work trends and merit critical consideration in scenario development. Many scenarios described 'new' or 'exacerbated' psychosocial hazards of work, whereas comparatively fewer discussed physical, chemical, or biological hazards. Various preventive recommendations were identified. In particular, reducing stress associated with precarious work and its requirements of continual skill preparation and training was acknowledged as critical for protecting and promoting the health and well-being of the future workforce. In conclusion, the future of work will be comprised of diverse complex scenarios and a mosaic of old and new hazards. These findings may serve as the basis for considering how to shape the future of work., (Published by Oxford University Press on behalf of The British Occupational Hygiene Society 2020.)

The development of the endovascular thrombectomy (EVT) technique has revolutionized acute stroke management for patients with large vessel occlusions (LVOs). The impact of successful recanalization using an EVT on autoregulatory profiles is unknown. A more complete understanding of cerebral autoregulation in the context of EVT may assist with post-procedure hemodynamic optimization to prevent complications. We examined cerebral autoregulation in 107 patients with an LVO in the anterior circulation (proximal middle cerebral artery (M1/2) and internal cerebral artery (ICA) terminus) who had been treated using an EVT. Dynamic cerebral autoregulation was assessed at multiple time points, ranging from less than 24 hours to 5 days following last seen well (LSW) time, using transcranial Doppler ultrasound recordings and transfer function analysis. Complete (Thrombolysis in Cerebral Infarction (TICI) 3) recanalization was associated with a more favorable autoregulation profile compared with TICI 2b or poorer recanalization ( p < 0.05), which is an effect that was present after accounting for differences in the infarct volumes. Less effective autoregulation in the first 24 h following the LSW time was associated with increased rates of parenchymal hematoma types 1 and 2 hemorrhagic transformations (PH1-PH2). These data suggest that patients with incomplete recanalization and poor autoregulation (especially within the first 24 h post-LSW time) may warrant closer blood pressure monitoring and control in the first few days post ictus.

Background: High-flow nasal cannula (HFNC) is a form of noninvasive respiratory support used for paediatric acute respiratory illnesses. Past HFNC research has focused on its use in bronchiolitis and in intensive care units, but little is reported on its use in the community hospital setting. We aimed to investigate the paediatric population using HFNC, any adverse events, and risk factors for deterioration., Methods: A retrospective chart review was performed on patients admitted to a community paediatric ward. Inclusion criteria were patients between 1 day and 17 years of age, admitted between September 2013 and April 2016, and treated with HFNC for at least 4 hours., Results: A total of 85 children met inclusion criteria. The average age of patients in our study was 3.41 years with 39% of patients >2 years of age. 46% of patients had an admitting diagnosis of bronchiolitis, 33% pneumonia, and 16% with asthma. Transfer rate to tertiary care centre paediatric intensive care unit was 18%. Patients transferred required greater FIO2 (odds ratio [OR] 1.04, P=0.018, confidence interval [CI] 1.007 to 1.082), and were 3.2 times more likely to be positive for respiratory syncytial virus (RSV) (P=0.081, CI 0.868-11.739). There were no adverse events attributed to HFNC in the population., Conclusion: HFNC is being utilized in the community hospital setting for children of varied age and types of respiratory illnesses. Children requiring higher FIO2 are at risk of respiratory deterioration which may identify them earlier for transfer to tertiary care. Further research into the safety and efficacy of HFNC for different paediatric illnesses in the community is needed., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose- We aimed to determine if microemboli after endovascular thrombectomy correlate with unfavorable outcomes despite successful recanalization. Methods- This is a prospective multicenter study of consecutive patients with ischemic stroke and occlusion of anterior circulation vessels (terminal internal carotid or main trunk of the middle cerebral artery/first-order branch of the main trunk of the middle cerebral artery segments of middle cerebral artery) after successful thrombectomy (modified Treatment In Cerebral Ischemia grades 2b-3). Microembolic signals (MES) were assessed by 30 minutes of transcranial Doppler monitoring within 72 hours of the last-seen-well time. Major outcomes included modified Rankin Scale at 90 days and infarct volume on head computed tomography at 24 hours. We also assessed early outcomes based on National Institutes of Health Stroke Scale variation and recurrence of stroke, transient ischemic attack, or systemic embolism within 90 days. Results- Among 111 patients, MES were detected in 43 (39%), with a median rate of 4 counts/h (interquartile range 2-12). The occurrence of MES was not associated with a significant difference in modified Rankin Scale (ordinal shift analysis, adjusted odds ratio, 1.06 [95% CI, 0.48-2.34] P =0.85) nor in functional independence (modified Rankin Scale, 0-2: adjusted odds ratio, 0.52 [95% CI, 0.19-1.39] P =0.19). Patients with and without MES had similar infarct volumes (adjusted beta, 11.2 [95% CI, -46.6 to +22.9] P =0.51) on 24-hour computed tomography. MES did predict new embolic events (adjusted Cox hazard ratio, 6.78 [95% CI, 1.63-27.8] P =0.01). Conclusions- MES detected by transcranial Doppler following endovascular treatment of anterior circulation occlusions do not predict clinical or radiological outcome. However, such emboli are an independent marker of recurrent embolic events within 90 days.

Objectives: Ischemic stroke due to large-vessel occlusion (LVO) is a complication after cardiothoracic surgery (CTS). Recently published endovascular stroke trials have major implications for treating LVO strokes; we evaluated our experience in patients undergoing CTS., Methods: Our prospective institutional CTS database was reviewed between July 2013 and April 2018 for ischemic strokes. Patients with LVO were identified and their course and outcomes analyzed., Results: A total of 5947 patients were reviewed; 148 (2.48%) had a cerebrovascular complication; 92.5% were ischemic. Of these 10.9% had an LVO. Prolonged aortic crossclamp was associated with LVO (odds ratio, 1.012 for every minute of prolonged aortic crossclamp time; confidence interval, 1.001-1.023) and remained significant in patients with ejection fraction >45%; prolonged cardiac bypass time was only associated with LVO in patients with ejection fraction >45% (odds ratio, 1.012 for every minute of prolonged cardiac bypass time; confidence interval, 1.003-1.021). Patients fell into 2 categories: detection of neurologic deficit in the stable postoperative patient or detection of deficit on emergence from anesthesia. Seven patients met criteria for emergent revascularization, with median National Institutes of Health Stroke Scale score 15, and shorter times from last seen well to deficit detection compared with patients not meeting criteria (P = .032). Median National Institutes of Health Stroke Scale day 7 score improved to 5. There was a trend toward better modified Rankin Scale scores at 3 months in patients who underwent thrombectomy., Conclusions: LVO complicates a small proportion of patients after CTS and may be more likely with prolonged aortic crossclamp and cardiac bypass times. Both early and late window endovascular stroke treatment has the potential to positively modify the complication profile of CTS. Greater awareness of this treatment option is needed., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: There is variability and uncertainty about the optimal approach to the management and discontinuation of an external ventricular drain (EVD) after subarachnoid hemorrhage (SAH). Evidence from single-center randomized trials suggests that intermittent CSF drainage and rapid EVD weans are safe and associated with shorter ICU length of stay (LOS) and fewer EVD complications. However, a recent survey revealed that most neurocritical care units across the United States employ continuous CSF drainage with a gradual wean strategy. Therefore, the authors sought to determine the optimal EVD management approach at their institution., Methods: The authors reviewed records of 200 patients admitted to their institution from 2010 to 2016 with aneurysmal SAH requiring an EVD. In 2014, the neurocritical care unit of the authors' institution revised the internal EVD management guidelines from a continuous CSF drainage with gradual wean approach (continuous/gradual) to an intermittent CSF drainage with rapid EVD wean approach (intermittent/rapid). The authors performed a retrospective multivariable analysis to compare outcomes before and after the guideline change., Results: The authors observed a significant reduction in ventriculoperitoneal (VP) shunt rates after changing to an intermittent CSF drainage with rapid EVD wean approach (13% intermittent/rapid vs 35% continuous/gradual, OR 0.21, p = 0.001). There was no increase in delayed VP shunt placement at 3 months (9.3% vs 8.6%, univariate p = 0.41). The intermittent/rapid EVD approach was also associated with a shorter mean EVD duration (10.2 vs 15.6 days, p < 0.001), shorter ICU LOS (14.2 vs 16.9 days, p = 0.001), shorter hospital LOS (18.2 vs 23.7 days, p < 0.0001), and lower incidence of a nonfunctioning EVD (15% vs 30%, OR 0.29, p = 0.006). The authors found no significant differences in the rates of symptomatic vasospasm (24.6% vs 20.2%, p = 0.52) or ventriculostomy-associated infections (1.3% vs 8.8%, OR 0.30, p = 0.315) between the 2 groups., Conclusions: An intermittent CSF drainage with rapid EVD wean approach is associated with fewer VP shunt placements, fewer complications, and shorter LOS compared to a continuous CSF drainage with gradual EVD wean approach. There is a critical need for prospective multicenter studies to determine if the authors' experience is generalizable to other centers.

Background: Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women., Methods: Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers was performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted an analysis of gene expression differences in P vs. NP women as a function of time since last FTP. Finally, a laser capture microdissection substudy was performed to compare the gene expression profile in the whole breast biopsy with that in the epithelial and stromal tissues., Results: Discovery/validation analysis identified 43 differentially expressed genes in P vs. NP breast. Analysis of expression as a function of time since FTP revealed 286 differentially expressed genes (238 up- and 48 downregulated) comparing all P vs. all NP, and/or P women whose last FTP was less than 5 years before biopsy vs. all NP women. The upregulated genes showed three expression patterns: (1) transient: genes upregulated after FTP but whose expression levels returned to NP levels. These genes were mainly related to immune response, specifically activation of T cells. (2) Long-term changing: genes upregulated following FTP, whose expression levels decreased with increasing time since FTP but did not return to NP levels. These were related to immune response and development. (3) Long-term constant: genes that remained upregulated in parous compared to nulliparous breast, independently of time since FTP. These were mainly involved in development/cell differentiation processes, and also chromatin remodeling. Lastly, we found that the gene expression in whole tissue was a weighted average of the expression in epithelial and stromal tissues., Conclusions: Genes transiently activated by FTP may have a role in protecting the mammary gland against neoplastically transformed cells through activation of T cells. Furthermore, chromatin remodeling and cell differentiation, represented by the genes that are maintained upregulated long after the FTP, may be responsible for the lasting preventive effect against breast cancer.

Although the impact the environment can have on human health is well understood, the healthcare system's impact on the environment is a topic that's only been explored since the mid-1990s. More recent has been a realization of the risks that climate change poses to health and healthcare. Although there are numerous direct benefits for hospitals adapting environmental sustainability programs, this article examines how the systemic approach taken by the University Health Network's (UHN) Energy & Environment program not only improves the hospital's environmental performance and provides significant cost savings but also supports several areas of focus that are part of UHN's current journey of renewal.

Background: The rarity of neuroendocrine malignancies limits the ability to develop new therapies and thus a better understanding of the underlying biology is critical., Methods: Through a prospective, IRB-approved protocol, patients with neuroendocrine malignancies underwent next-generation sequencing of their tumours to detect somatic mutations (SMs) in 50 cancer-related genes. Clinicopathologic correlation was made among poorly differentiated neuroendocrine carcinomas (NECs/poorly differentiated histology and Ki-67 >20%) and pancreatic neuroendocrine tumours (PanNETs/Ki67 ⩽20%) and non-pancreatic neuroendocrine tumours (NP-NETs/Ki67 ⩽20%)., Results: A total of 77 patients were enrolled, with next-generation sequencing results available on 63 patients. Incidence of SMs was 83% (19 out of 23) in poorly differentiated NECs, 45% (5 out of 11) in PanNETs and 14% (4 out of 29) in NP-NETs. TP53 was the most prevalent mutation in poorly differentiated NECs (57%), and KRAS (30%), PIK3CA/PTEN (22%) and BRAF (13%) mutations were also found. Small intestinal neuroendocrine tumours (Ki67 <2%/n=9) did not harbour any mutations. Prevalence of mutations correlated with higher risk of progression within the previous year (32% (low risk) vs 11% (high risk), P=0.01) and TP53 mutation correlated with worse survival (2-year survival 66% vs 97%, P=0.003)., Conclusions: Poorly differentiated NECs have a high mutation burden with potentially targetable mutations. The TP53 mutations are associated with poor survival in neuroendocrine malignancies. These findings have clinical trial implications for choice of therapy and prognostic stratification and warrant confirmation.

Sex trafficking (ST), a contemporary form of female slavery, is a human rights issue of critical concern to social work. The global response to ST has been substantial, and 166 countries have adopted anti-ST legislation. Despite considerable efforts to combat ST, the magnitude is increasing. To date, the majority of anti-ST efforts have focused on criminalization policies that target traffickers or purchasers of sexual services, who are predominantly male; prevention programming and services for predominantly female victims have received less support. Therapeutic services to assist pornography addicts and purchasers of sexual services are also necessary. In this article, authors examine current anti-ST policies, programs, and services, both domestically and globally, and present an innovative paradigm that addresses social inequities and emphasizes prevention programming. They conclude with a discussion of the paradigm's implications for social work policies, practices, and services.

Pregnancy and its effects on breast cancer risk have been widely investigated; there is consensus among researchers that early pregnancy confers protection against breast cancer later in life, whereas nulliparity and late-age parity have been associated with increased risk of developing breast cancer. The answer to the question of how pregnancy reduces breast cancer risk has been elusive; however, pregnancy, like breast cancer, is a similar hormone-dependent entity under direct control of estrogen, progesterone and, of particular importance, human chorionic gonadotropin (hCG). In this report, we emphasize the main changes, previously described by our laboratory, in morphology and gene expression levels of the mammary gland of Sprague-Dawley rats exposed to known cancer-preventative conditions (pregnancy, hCG and progesterone + estrogen). In addition, we postulate a protective mechanism induced by hCG that could reduce the cell's potential to be transformed by carcinogens.

Background: It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy., Methods: In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry., Results: We identified 305 differentially expressed probesets (208 distinct genes). Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis., Conclusions: This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process.

Early pregnancy and multiparity are known to reduce the risk of women to develop breast cancer at menopause. Based on the knowledge that the differentiation of the breast induced by the hormones of pregnancy plays a major role in this protection, this work was performed with the purpose of identifying what differentiation-associated molecular changes persist in the breast until menopause. Core needle biopsies (CNB) obtained from the breast of 42 nulliparous (NP) and 71 parous (P) postmenopausal women were analyzed in morphology, immunocytochemistry and gene expression. Whereas in the NP breast, nuclei of epithelial cells were large and euchromatic, in the P breast they were small and hyperchromatic, showing strong methylation of histone 3 at lysine 9 and 27. Transcriptomic analysis performed using Affymetrix HG&#95;U133 oligonucleotide arrays revealed that in CNB of the P breast, there were 267 upregulated probesets that comprised genes controlling chromatin organization, transcription regulation, splicing machinery, mRNA processing and noncoding elements including XIST. We concluded that the differentiation process induced by pregnancy is centered in chromatin remodeling and in the mRNA processing reactome, both of which emerge as important regulatory pathways. These are indicative of a safeguard step that maintains the fidelity of the transcription process, becoming the ultimate mechanism mediating the protection of the breast conferred by full-term pregnancy., (Copyright © 2011 UICC.)

Using a cross-sectional design, this study utilized a self-administered survey to examine the relationship between acculturation, physical and emotional health, health locus of control (LOC), life events and depression among a convenient sample of 70 immigrant Muslim elderly in United States of America. In addition to demographic variables, 5 standardized measures including the Vancouver Index of Acculturation, Center for Epidemiologic Studies Depression Scale (CESD), Iowa Self-Assessment Inventory, Multidimensional Health Locus of Control Scale, and the Geriatric Scale of Recent Life Events were utilized in this study. The results showed that about 50% of participants reported a score of 16 and above on the CESD scale, indicating a presence of depressive symptoms. In addition, most participants identified with their heritage culture compared to the American culture. The results of multiple regression analysis revealed 4 significant predictors of depression: cognitive status (β = -.34, p < .01), heritage culture (β = .35, p < .01), physical health (β = -.27, p < .05), and internal health locus of control (β = -.25, p < .05). These factors explain about 37% of the total variance in levels depression (R = .61).

Our studies are aimed at determining whether pregnancy induces a specific genomic signature in the postmenopausal breast that is responsible for the protective effect elicited by this physiological process. For this purpose we designed a study to compare the gene expression profiles in normal breast tissue from parous postmenopausal women with (case) and without (control) breast cancer. We have used breast samples from 18 parous controls and 41 parous cases. The epithelium and the interlobular stroma were dissected using laser capture microdissection and the RNA of each compartment and each sample was isolated, amplified using PCR methodology, and hybridized to cDNA glass-microarrays containing 40,000 genes, placing the human reference RNA in the green channel (Cy3) and the breast tissue samples in the red channel (Cy5). The normalization and statistical analysis of the expression data were carried out by using the LIMMA software package for the R programming environment which provides functions to summarize the results using the linear model perform hypothesis tests and adjust the p-values for multiple testing. We were able to identify 126 genes that were upregulated and 103 that were downregulated in the parous control group. There were only 56 genes differentially expressed in the interlobular stroma in the parous control group in relation to the other group of women under study. The gene categories that were overrepresented in the breast epithelium of the parous control breast are related to apoptosis, DNA repair, response to exogenous agents and transcription regulation. In the present study we demonstrate that full-term pregnancy imprints a specific genomic signature in the breast epithelium of postmenopausal parous control women that is significantly different from women who have developed cancer. This genomic signature induced by pregnancy could help to predict in which women parity is protective.

Metabolic conversion of endogenous estrogens, estradiol (E2) and estrone (E1), to the catechol estrogens 4-hydroxyE1(E2) [4-OHE1(E2)] has been implicated in the initiation of cancer in rodents and humans. Evidence collected in our laboratories has shown that 4-OHE1(E2) are enzymatically oxidized to E1(E2)-3,4-quinones [E1(E2)-3,4-Q], which have the potential to damage DNA by forming predominantly depurinating adducts, 4-OHE1(E2)-1-N3Ade and 4-OHE1(E2)-1-N7Gua, leading to the accumulation of mutations and probably cell transformation. The human breast epithelial cell line MCF-10F has been transformed by treatment with E2 or 4-OHE2. We have used MCF-10F cells to study the presence of adducts and conjugates after treatment with 4-OHE2. To mimic the intermittent exposure of breast cells to endogenous estrogens, MCF-10F cells were treated with 1 microM 4-OHE2 for a 24-h period at 72, 120, 192 and 240 h postplating. Culture media were collected at each point, extracted by solid-phase extraction and analyzed by HPLC connected with a multichannel electrochemical detector and/or ultraperformance liquid chromatography/tandem mass spectrometry. Media from successive treatments with 4-OHE2 showed the formation of methoxy and cysteine conjugates, and the depurinating adducts 4-OHE1(E2)-1-N3Ade. The amount of 4-OHE1(E2)-1-N3Ade adducts was higher after the third treatment; smaller amounts of the 4-OHE1(E2)-1-N7Gua adducts were detected after the second and third treatments. These results demonstrate that MCF-10F cells oxidize 4-OHE2 to E1(E2)-3,4-Q, which react with DNA to form the depurinating N3Ade and N7Gua adducts. This DNA damage can play an important role in the 4-OHE2-induced mutations and transformation of MCF-10F cells to malignant cells., ((c) 2007 Wiley-Liss, Inc.)

We have postulated that the lifetime protective effect of an early pregnancy against breast cancer is due to the complete differentiation of the mammary gland characterized by a specific genomic signature imprinted by the physiological process of pregnancy. In the present work, we show evidence that the breast tissue of postmenopausal parous women has had a shifting of stem cell 1 to stem cell 2 with a genomic signature different from similar structures derived from postmenopausal nulliparous women that have stem cell 1. Those genes that are significantly different are grouped in major categories on the basis of their putative functional significance. Among them are those gene transcripts related to immune surveillance, DNA repair, transcription, chromatin structure/activators/co-activators, growth factor and signal transduction pathway, transport and cell trafficking, cell proliferation, differentiation, cell adhesion, protein synthesis and cell metabolism. From these data, it was concluded that during pregnancy there are significant genomic changes that reflect profound alterations in the basic physiology of the mammary gland that explain the protective effect against carcinogenesis. The implication of this knowledge is that when the genomic signature of protection or refractoriness to carcinogenesis is acquired by the shifting of stem cell 1 to stem cell 2, the hormonal milieu induced by pregnancy or pregnancy-like conditions is no longer required. This is a novel concept that challenges the current knowledge that a chemopreventive agent needs to be given for a long period to suppress a metabolic pathway or abrogate the function of an organ.

We have postulated that the lifetime protective effect of an early pregnancy against breast cancer is due to the complete differentiation of the mammary gland characterized by a specific genomic signature imprinted by the physiological process of pregnancy. For demonstrating this hypothesis we compared the genomic profile of the epithelium and the stroma of normal breast tissues from reduction mammoplasties performed in postmenopausal parous and nulliparous women. The epithelium and the stroma were separately dissected using laser capture microdissection (LCM) and the RNA of each compartment and each sample was isolated, amplified using PCR methodology, and hybridized to cDNA glass-microarrays containing 40,000 human cDNA features. The separation of the epithelial compartment from the interlobular stroma of Lob 1 using LCM allowed us to determine that the epithelial component contained 4,828 genes that were equally expressed in both nulliparous and parous women. There were 73 known genes that included immune-modulation-, DNA repair-, programmed cell death-, chromatin remodeling- and transcription-related genes, whereas in the breast of nulliparous women there were 20 different known genes that were upregulated. Our data provide evidence that breast tissues of postmenopausal parous women express in both the epithelial and the stromal compartments numerous genes that differ significantly from those present in breast tissues of post-menopausal nulliparous women, which could be important contributors to the genomic signature induced by an early full term pregnancy.

The breast attains its maximum development during pregnancy and lactation. After menopause the breast regresses in both nulliparous and parous women containing lobular structures that have been designated lobules type 1. Despite the similarity in the lobular composition of the breast at menopause, the fact that nulliparous women are at higher risk of developing breast cancer than parous women, indicates that Lobules type 1 in these two groups of women might be biologically different, or exhibit different susceptibility to carcinogenesis. Based on these observations it was postulated that the Lobule type 1 found in the breast of nulliparous women and of parous women with breast cancer never went through the process of differentiation, retaining a high concentration of epithelial cells that are targets for carcinogens and therefore susceptible to undergo neoplastic transformation, these cell are called Stem cells 1, whereas Lobules type 1 structures found in the breast of early parous postmenopausal women free of mammary pathology, on the other hand, are composed of an epithelial cell population that is refractory to transformation called Stem cells 2. It was further postulated that the degree of differentiation acquired through early pregnancy has changed the "genomic signature" that differentiates the Lobule type 1 from the early parous women from that of the nulliparous women by shifting the Stem cell 1 to a Stem cell 2 that is refractory to carcinogenesis, making this the postulated mechanism of protection conferred by early full term pregnancy. The identification of a putative breast stem cell (Stem cell 1) has reached in the last decade a significant impulse and several markers also reported for other tissues have been found in the mammary epithelial cells of both rodents and humans. Although still more work needs to be done in order to better understand the role of the Stem cell 2 and its interaction with the genes that confer it a specific signature, collectively, the data presently available provides evidence that pregnancy, through the process of cell differentiation, shifts the Stem cell 1 to Stem cell 2, cells that exhibit a specific genomic signature that could be responsible for the refractoriness of the mammary gland to carcinogenesis.

Sporadic breast cancer is a fatal disease most frequently diagnosed in American women from all ethnic groups, suggesting that primary prevention should be the ultimate goal for breast cancer control. We have developed a novel paradigm for breast cancer prevention arising from the well-established knowledge that an early first full-term pregnancy protects the breast against neoplastic transformation, as well as from our studies of the biological principle underlying this protection. We have shown experimentally that the first pregnancy induces the expression of a specific genomic signature in the breast that results from the completion of a cycle in this organ's differentiation driven by the reproductive process. This signature, in turn, is a biomarker associated with a possible overall lifetime decrease in breast cancer risk. We have shown in an experimental model that a short treatment with human chorionic gonadotropin, a placental hormone secreted during pregnancy, induces the same genomic signature that occurs in pregnancy, inhibiting not only the initiation but also the progression of mammary carcinomas, and stopping the development of early lesions such as intraductal proliferations and carcinoma in situ. These observations indicate that human chorionic gonadotropin given for a very short period, only until this genomic signature is acquired, has significant potential as a chemopreventive agent, protecting the normal cell from becoming malignant. This is a novel concept which challenges the current knowledge that a chemopreventive agent needs to be given for a long period of time to suppress a metabolic pathway or abrogate the function of an organ.

All three cost-saving initiatives--the creation of a one-page application form to streamline the rehabilitation application process, the use of the resource specialist to assist with applications, and the development of an information package on cardiac rehabilitation--reflect a process whereby a creative idea, generating planning, activities, and follow-up resulted in a measurable effective change in practice. This process truly translated strategy into action (Kaplan, 1996) and is vital to the current rethinking in health care of how best to do our work (Coan, 1994). Because of this process, social workers in the cardiovascular surgical division of the cardiac program are better equipped to respond to the psychosocial needs of a growing cardiac population in a fiscally restrained environment.

Setting: Large academic medical center in Tanzania., Objectives: To determine the etiologies and outcomes of large pericardial effusions in HIV-infected and uninfected patients., Design: Prospective cohort study of patients admitted with new large pericardial effusions, confirmed echocardiographically. Patients had pericardial biopsies and drainage with extensive analysis of tissue and fluid specimens, and were followed with clinical and echocardiographic examinations., Results: Of 28 patients with large pericardial effusions, 19 were infected with HIV-1. 22 had invasive diagnostic procedures: 14 of 14 HIV-infected patients, but only 4 of 8 non-HIV-infected patients, had tuberculous pericarditis (P = 0.01). All but 1 of the HIV-infected patients had strongly positive tuberculin skin tests, and short-term outcomes were similar in the 2 groups., Conclusion: TB is the predominant cause of large pericardial effusion in HIV-infected patients in this setting; non-HIV-infected patients are more likely to have other etiologies. These patients were at an early stage of HIV infection and responded well to treatment. In settings where microbiological studies are not routinely available, HIV-infected patients with large pericardial effusions may be treated empirically for tuberculosis and monitored for improvement. If improvement does not follow within 2-4 weeks further studies are indicated. HIV-negative patients should undergo diagnostic evaluation initially.