Setting positive end-expiratory pressure: does the 'best compliance' concept really work?

PURPOSE OF REVIEW: Determining the optimal positive end-expiratory pressure (PEEP) setting remains a central yet debated issue in the management of acute respiratory distress syndrome (ARDS).The 'best compliance' strategy set the PEEP to coincide with the peak respiratory system compliance (or 2 cmH 2 O higher) during a decremental PEEP trial, but evidence is conflicting. RECENT FINDINGS: The physiological rationale that best compliance is always representative of functional residual capacity and recruitment has raised serious concerns about its efficacy and safety, due to its association with increased 28-day all-cause mortality in a randomized clinical trial in ARDS patients.Moreover, compliance measurement was shown to underestimate the effects of overdistension, and neglect intra-tidal recruitment, airway closure, and the interaction between lung and chest wall mechanics, especially in obese patients. In response to these concerns, alternative approaches such as recruitment-to-inflation ratio, the nitrogen wash-in/wash-out technique, and electrical impedance tomography (EIT) are gaining attention to assess recruitment and overdistention more reliably and precisely. SUMMARY: The traditional 'best compliance' strategy for determining optimal PEEP settings in ARDS carries risks and overlooks some key physiological aspects. The advent of new technologies and methods presents more reliable strategies to assess recruitment and overdistention, facilitating personalized approaches to PEEP optimization.

Prevalence and factors associated with mental health status in Parkinson's disease: Data from the 45 and Up Study.

INTRODUCTION: Parkinson's disease (PD) is associated with a range of non-motor symptomologies such as anxiety and depression. OBJECTIVE: The purpose of this research was to investigate the prevalence and factors associated with mental health status in persons with PD. DESIGN: This retrospective data linkage study analysed a subset of data from the Sax Institute's 45 and Up Study based in the population of the state of New South Wales (NSW), Australia. Data was analysed between 2005-2009 of persons who self-identified with PD. Secure data access was provided through the Sax Institute's Secure Unified Research Environment (SURE). Participants were aged 45+ years of age and living in NSW, Australia. Regression analysis was performed on psychological distress (K10), previous diagnosis of anxiety, and/or depression, with independent variables for locality, demographic, health, medical, and sociocultural factors. FINDINGS: A total of 1676 persons self-identified with PD from the 45 and Up Study Wave 1 baseline and were linked to the 2010 Social, Economic and Environmental Factors (SEEF) survey dataset. Mental health manifestations are common in PD with 29% and 32% reporting a previous medical diagnosis of anxiety and depression, respectively. Rural locality was associated with an increased likelihood of psychological distress, anxiety, and depression compared to metropolitan locality. DISCUSSION: Mental health status in PD was associated with living in rural areas, medical service access, female gender, ageing, physical mobility, Australian born, social interactions, and in a coupled relationship. CONCLUSION: Further research is required on the longitudinal impact of these associations on mental health in PD.

Theoretical Feasibility of Using Arch Branched Endograft Devices for Repair of Post Type A Aortic Dissection in Patients With Prior Ascending Aortic Replacement.

PURPOSE: Ascending aortic replacement is a common emergency procedure for treating acute type A aortic dissection. Secondary open or endovascular interventions for residual arch pathologies is difficult because of adhesions, short prosthetic grafts, and distorted anatomies. Aortic arch branched stent grafts have emerged as a potential solution for these patients if they have suitable anatomical conditions. This study aimed to evaluate the theoretical anatomical and technical feasibility of 2 currently used aortic arch branch endografts in patients who had prior replacement of the ascending aorta. MATERIALS AND METHODS: All patients who had a prosthetic ascending aortic or hemiarch replacement for acute type A dissection in a single institution between January 2013 and December 2018 were included. Contrast computed tomography images on the most recent follow-up were analyzed on a 3-dimensional workstation. Morphological parameters were measured individually for the ascending aorta, aortic arch, supra-aortic branches, and access iliac arteries. The computed tomography scan of each patient was individually evaluated for anatomical suitability for the arch branched and double-branch devices according to set selection criteria. RESULTS: Computed tomography images of 56 patients (median age of 57 years, 45 males) were reviewed. Based on our evaluation, 26 patients (46.4%) were good candidates for an endovascular arch branched device. It would be feasible for 13 patients (23.2%), but prudent preoperative planning was required due to complicated anatomy. The other 17 patients (30.4%) were unsuitable because they met at least 1 exclusion criterion. Short prosthetic grafts, extreme graft angulations, and extensive dissections in the supra-aortic branches were the main reasons for exclusion. CONCLUSION: Endovascular repair using arch branched endografts is feasible in patients with prior ascending aortic arch or hemiarch replacement for acute type A aortic dissection. The most common anatomical conditions that may influence the feasibility of the arch branched endograft procedure include insufficient proximal seal length, severe angulation of the graft, and extensive aortic dissection within the supra-aortic vessels.

ECMO simulation training during a worldwide pandemic: The role of ECMO telesimulation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy used in the most severe forms of acute respiratory distress syndrome. Due to its intrinsic complexity and relatively low annual volume, simulation is essential for efficient and appropriate ECMO management. COVID-19 has limited the opportunities for high-fidelity in-person simulation training when many hospitals are looking to expand their ECMO services to battle the ongoing pandemic. To meet this demand, the National Cardiovascular Center Harapan Kita, Jakarta, Indonesia, conducted a 3-day ECMO course entailing online didactic lectures (adult and paediatric stream), water drills and telesimulation. PURPOSE: The purpose of the study is to report the evaluation result of this novel model of education during COVID-19 outbreak. DATA COLLECTION: Participants were given an ECMO knowledge pre-course and post-course test and a telesimulation evaluation survey at the conclusion and these data were collected. RESULTS: The course was attended by 104 physicians, critical care nurses and perfusionists. Pre-course and post-course assessments showed a significant improvement in ECMO knowledge (60.0% vs 73.3%, respectively). Overall, the participants rated the telesimulation positively, and most found it acceptable to in-person simulation training considering the pandemic restrictions. CONCLUSION: Despite the complexities of ECMO, our recent experience demonstrates ECMO education and simulation delivered online is feasible, welcomed and supportive of a change in ECMO training course format. As we incorporate more innovative digital technologies, telesimulation may further enhance the quality of future ECMO training.

Exploring Parkinson's disease prevalence in regional, rural and remote Australia: A systematic scoping review.

INTRODUCTION: Idiopathic Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Due to ageing populations, prevalence estimates for PD are set to increase in western countries including Australia. OBJECTIVE: This study aims to investigate the prevalence of PD in regional, rural and remote areas of Australia, to inform the provision of equitable PD-specific care. DESIGN: A scoping review, following the Joanna Briggs Institute methodology for scoping reviews and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), was conducted. An electronic search of four databases and the search engine google scholar was completed in May 2022 and updated in September 2023. Article screening and quality appraisal were undertaken independently by at least two reviewers. FINDINGS: Of 514 records screened, six articles (between 1966 and 2019) were identified and included for review. Wide variations in PD prevalence were evident, ranging from 0.58 to 8.5 per 1000 people. Two studies suggested prevalence may be higher in regional, rural and remote areas of Australia than in urban localities. DISCUSSION: The limited number of studies identified, and wide variation in prevalence rates makes it difficult to draw firm conclusions to inform heath care planning and resource allocation. CONCLUSION: A paucity of reliable prevalence data indicates the need for well-designed, country-specific epidemiological studies to be conducted to estimate the actual impacts of the disease to inform public health planning, particularly in regional, rural and remote areas where access to PD-specific care is already inequitable.

Using an economic evaluation approach to support specialist nursing services for people with Parkinson's in a regional community.

AIM: This study aims to provide economic evidence of the cost-effectiveness of employing specialist Parkinson's nurses in a regional community in Australia. STUDY DESIGN: This retrospective study utilized hospital service usage data to compare outcomes for people with Parkinson's disease before and after the employment of a specialist Parkinson's nurse in a regional community. METHODS: A representative sample was drawn from the target population of people with a diagnosis of Parkinson's admitted to a regional hospital over a 4-year period (2013-2014 and 2016-2017). A multiple regression approach and cost-benefit analysis were used to examine hospital costs related to length of stay based on hospital records. All costs were attributed to resource allocation according to service category and the national funding system. Quantitative data were analysed using Strata Analytics. RESULTS: Statistical findings demonstrated a reduction in hospital length of stay ranging from 0.37 (AUD$1924) to 0.755 day (AUD$3926) after the establishment of the specialist Parkinson's nurse. The cost-benefit analysis showed a net dollar benefit, or savings in hospital costs, of up to $8600.00 per person over a 3-year period, as a result of the specialist Parkinson's nurse intervention. CONCLUSION: The statistical results show significant cost benefits associated with reduced length of hospital stay following introduction of the specialist Parkinson's nurse. These findings support advocacy for sustainable specialist Parkinson's nurse positions and have the potential to inform and influence policy and systemic changes within the health care system. IMPACT: The benefits of embedding specialist nursing services for people with Parkinson's disease in primary health settings include the direct impact on the potential to avoid hospital admissions due to worsening symptoms, improving quality of life for the person with Parkinson's and slowing the trajectory of the disease. Additional benefits are increased access to specialist services and reduced family caregiver burden.

Mental health and well-being impacts of COVID-19 on rural paramedics, police, community nurses and child protection workers.

OBJECTIVE: To investigate the impact of COVID-19 on the mental health and well-being of rural paramedics, police, community nursing and child protection staff. METHOD: An online survey was distributed to investigate the sources of stress and support across individual, task and organisational domains. SETTING AND PARTICIPANTS: The survey was completed by 1542 paramedics, police, community nurses and child protection workers from all states and territories of Australia. This study describes the data for the 632 rural participants. MAIN OUTCOME MEASURES: The main measures of well-being were the Public Health Questionnaire (PHQ9), the Generalised Anxiety Disorder (GAD7), the Maslach Burnout Inventory (MBI), workplace engagement, intention to quit and COVID-19-related stress. RESULTS: The mean depression and anxiety scores were 8.2 (PHQ9) and 6.8 (GAD7). This is 2-3 times that found in the general community. Over half (56.1%) of respondents showed high emotional exhaustion (burnout). The emotional exhaustion, depersonalisation and personal accomplishment mean scores were 28.5, 9.3 and 34.2, respectively. The strongest associations with burnout and psychological distress were workload, provision of practical support, training and organisational communication. A significant proportion of respondents were seriously considering quitting (27.4%) or looking for a new job with a different employer (28.5%) in the next 12 months. CONCLUSIONS: COVID-19 has increased the workload and stress on rural front-line community staff. The major sources of stress were related to organisations' responses to COVID-19 and not COVID-19 per se. The data suggest the most effective mental health interventions are practical and preventive, such as firstly ensuring fair and reasonable workloads.

An anti-CD3/anti-CLL-1 bispecific antibody for the treatment of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a major unmet medical need. Most patients have poor long-term survival, and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacologic activity, pharmacokinetics, and safety of a CD3 T cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML. CLL-1 is prevalent in AML and, unlike other targets such as CD33 and CD123, is not expressed on hematopoietic stem cells providing potential hematopoietic recovery. We selected a high-affinity monkey cross-reactive anti-CLL-1 arm and tested several anti-CD3 arms that varied in affinity, and determined that the high-affinity CD3 arms were up to 100-fold more potent in vitro. However, in mouse models, the efficacy differences were less pronounced, probably because of prolonged exposure to TDB found with lower-affinity CD3 TDBs. In monkeys, assessment of safety and target cell depletion by the high- and low-affinity TDBs revealed that only the low-affinity CD3/CLL1 TDB was well tolerated and able to deplete target cells. Our data suggest that an appropriately engineered CLL-1 TDB could be effective in the treatment of AML.

Antiviral Effects and Mechanisms of Green Tea Catechins on Influenza: A Perception on Combating Symptoms from COVID-19.

Over the centuries, influenza and its associated epidemics have been a serious public health problem. Although vaccination and medications (such as neuraminidase inhibitors) are the mainstay of pharmacological approaches to prevent and treat influenza, however, frequent mutations in the influenza genome often result in treatment failure and resistance to standard medications which limit their effectiveness. In recent years, green tea catechins have been evaluated as potential anti-influenza agents. Herein, in this review, we highlighted the effects and mechanisms underlying the inhibitory effects of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea, against different influenza viral infections, and their clinical benefits toward prevention and treatment. In addition, as the severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) causes the outbreak of COVID-19 pandemic, our review also delineates the current perspective on SARS-CoV-2 and future insights as to the potential application of EGCG on suppressing the flu-like symptoms caused by COVID-19.

Effects of varying blood flow rate during peripheral veno-arterial extracorporeal membrane oxygen (V-A ECMO) on left ventricular function measured by two-dimensional strain.

Background: We evaluated the effects of varying blood flow rate during peripheral veno-arterial extracorporeal membrane oxygen (V-A ECMO) on left ventricular function measured by two-dimensional strain. Methods: Adult patients who were supported by peripheral V-A ECMO were recruited. Serial hemodynamic and cardiac performance parameters were measured by transthoracic echocardiogram within the first 48 h after implementation of V-A ECMO. Measurements at 100%, 120%, and 50% of target blood flow (TBF) were compared. Results: A total of 54 patients were included and the main indications for V-A ECMO were myocardial infarction [32 (59.3%)] and myocarditis [6 (11.1%)]. With extracorporeal blood flow at 50% compared with 100% TBF, the mean arterial pressure was lower [66 ± 19 vs. 75 ± 18 mmHg, p < 0.001], stroke volume was greater [23 (12-34) vs. 15 (8-26) ml, p < 0.001], and cardiac index was higher [1.2 (0.7-1.7) vs. 0.8 (0.5-1.3) L/min/m2, p < 0.001]. Left ventricular contractile function measured by global longitudinal strain improved at 50% compared with 100% TBF [-2.8 (-7.6- -0.1) vs. -1.2 (-5.2-0) %, p < 0.001]. Similarly, left ventricular ejection fraction increased [24.4 (15.8-35.5) vs. 16.7 (10.0-28.5) %, p < 0.001] and left ventricular outflow tract velocity time integral increased [7.7 (3.8-11.4) vs. 4.8 (2.5-8.5) cm, p < 0.001]. Adding echocardiographic parameters of left ventricular systolic function to the Survival After Veno-arterial ECMO (SAVE) score had better discriminatory value in predicting eventual hospital mortality (AUROC 0.69, 95% CI 0.55-0.84, p = 0.008) and successful weaning from V-A ECMO (AUROC 0.68, 95% CI 0.53-0.83, p = 0.017). Conclusion: In the initial period of V-A ECMO support, measures of left ventricular function including left ventricular ejection fraction and global longitudinal strain were inversely related to ECMO blood flow rate. Understanding the heart-ECMO interaction is vital to interpretation of echocardiographic measures of the left ventricle while on ECMO.

A prospective study on serum citrate levels and clinical correlations in patients receiving regional citrate anticoagulation.

Background: Current ways to diagnose citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) are confounded by various clinical factors. Serum citrate measurement emerges as a more direct way to diagnose CA, but its clinical utility and optimal cut-off values remain undefined. This study examined serum citrate kinetics and its diagnostic performance for CA in patients receiving RCA CRRT. Methods: A multicentre prospective study was carried out in two tertiary referral centre intensive care units in Hong Kong with serum citrate levels measured at baseline and 2, 6, 12, 24, 36, 48 and 72 h after initiation of RCA CRRT and their relationships with the development of CA. Results: Among the 133 patients analysed, 18 patients (13.5%) developed CA. The serum citrate levels at baseline and 2, 6 and 12 h after initiation of RCA CRRT in patients who had CA were significantly higher than the non-CA group (P < .001 for all). The CA group also had higher serum citrate levels than the non-CA group {median 0.93 mmol/L [interquartile range (IQR) 0.81-1.16) versus 0.37 mmol/L (IQR 0.26-0.57), P < .001}. Using a cut-off of 0.85 mmol/L, the serum citrate level had a sensitivity of 0.77 and a specificity 0.96 for the diagnosis of CA [area under the receiver operating characteristics curve (AUROC) 0.90, P < .001]. The 2-h and 6-h serum citrate levels had good discriminatory abilities for predicting subsequent development of CA (AUROC 0.86 and 0.83 for 2-h and 6-h citrate levels using cut-off values of 0.34 and 0.63 mmol/L, respectively; P < .001). Conclusion: Serum citrate levels were significantly higher in patients with CA compared with patients without CA. Serum citrate levels showed good performance in diagnosing and predicting the development of CA.

Buttock Ischemia in Venoarterial Extracorporeal Membrane Oxygenation: A Case Series.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a bridging therapy for refractory cardiogenic shock, and limb ischemia is a concern with femoral cannulation. Because of the rich collateral pelvic circulatory supply, buttock ischemia is not common and is usually a complication after aneurysmal aortic repair or internal iliac artery embolization after pelvic trauma. Gluteal necrosis occurring as an extracorporeal membrane oxygenation complication has not been reported in the literature. In this case series, we report three patients with ischemic buttock after initiating VA-ECMO and discuss the risk factors and the clinical and radiological features supportive of the diagnosis. We review the gluteal and pelvic vascular anatomy, postulate how cannula size, ethnicity, catecholamines, and reversal of gluteal arterial flow contributed to this rare entity in our patients and explain how these findings have changed our institution's practice.

Monomeric C-reactive protein induces the cellular pathology of Alzheimer's disease.

Introduction: Human study shows that elevated C-reactive protein (CRP) in blood impacts apolipoprotein E (APOE) ε4, but not APOE ε3 or APOE ε2, genotype to increase the risk of Alzheimer's disease (AD). However, whether CRP is directly involved in cellular AD pathogenesis and in which type of neuronal cells of APOE ε4 carriers are unknown. Methods: We aimed to use different primary neuronal cells and investigate if CRP induces cellular AD pathology depending on APOE genotypes. Here the different primary neuronal cells from the different APOE genotype knock-in mice cortex were isolated and used. Results: Monomeric CRP (mCRP) increased amyloid beta production and, in parallel, induced tau phosphorylation in addition to their related proteins in the primary neurons in a pattern of APOE ε4 > APOE ε3 > APOE ε2 in a dose- and time-dependent manner. Consistently, mCRP induced the staining of other neurodegenerative biomarkers, including Fluoro-Jade B stain (FjB), TUNEL and Cleaved Caspase-3, in primary neurons in a similar pattern of APOE ε4 > APOE ε3 > APOE ε2. In contrast, pentameric CRP (pCRP) had a tendency to induce cellular AD pathology but did not reach statistical significance. On the other hand, it is intriguing that regardless of APOE genotype, mCRP did not influence the expressions of Iba-1 and CD68 in primary microglia or the expression of glial fibrillary acidic protein in primary astrocytes, and additionally mCRP did not affect the secretions of interleukin (IL)-1α, IL-1ß, and tumor necrosis factor α from these cells. Discussion: This is the first report to demonstrate that mCRP directly induces cellular AD pathogenesis in neurons in an APOE genotype-dependent pattern, suggesting that mCRP plays a role as a mediator involved in the APOE ε4-related pathway for AD during chronic inflammation. Highlights: Pentameric C-reactive protein (pCRP) can be dissociated irreversibly to form free subunits or monomeric CRP (mCRP) during and after the acute phase.mCRP increased amyloid beta production in the primary neurons in a pattern of apolipoprotein E (APOE) ε4 > APOE ε3 > APOE ε2 in a dose-dependent manner.mCRP induced the expression of phosphorylated tau in the primary neurons in a pattern of APOE ε4 > APOE ε3 > APOE ε2 in a dose- and time-dependent manner.mCRP plays an important mediator role in the APOE ε4-related pathway of Alzheimer's disease risk.

Short-term mechanical circulatory support (intra-aortic balloon pump, Impella, extracorporeal membrane oxygenation, TandemHeart): a review.

Cardiogenic shock remains a major cause of morbidity and mortality for patients with acute myocardial infarction and advanced heart failure. Intra-aortic balloon pump has been the most widely used short-term mechanical circulatory support device to rapidly stabilize hemodynamics. However, it provides modest support, current evidence does not show a decrease in mortality, and the latest guidelines no longer recommend its routine use. Several percutaneous mechanical circulatory support devices have been introduced into clinical practice (Impella, extracorporeal membrane oxygen, TandemHeart), providing a greater level of hemodynamic support. These resource-intensive devices demand a careful selection of patients that stand to benefit the most. Premature initiation of mechanical circulatory support exposes the patient to unnecessary risk, whereas delaying therapy leads to irreversible end-organ injury, rendering any intervention medically futile. Cannulation methods, pump designs, and circuit configurations differ between devices, as do the adverse effects and physiological impact on the myocardium, which needs to be factored into consideration before deployment on the patient in cardiogenic shock. This article will review the commonly used percutaneous mechanical circulatory support devices in the setting of cardiogenic shock, compare their advantages and disadvantages, evaluate key clinical trials, and discuss a practical approach to guide clinicians' decision and management.

The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells.

The dysregulation of multiple signaling pathways, including those through endosomal Toll-like receptors (TLRs), Fc gamma receptors (FcγR), and antigen receptors in B cells (BCR), promote an autoinflammatory loop in systemic lupus erythematosus (SLE). Here, we used selective small-molecule inhibitors to assess the regulatory roles of interleukin-1 receptor (IL-1R)-associated kinase 4 (IRAK4) and Bruton's tyrosine kinase (BTK) in these pathways. The inhibition of IRAK4 repressed SLE immune complex- and TLR7-mediated activation of human plasmacytoid dendritic cells (pDCs). Correspondingly, the expression of interferon (IFN)-responsive genes (IRGs) in cells and in mice was positively regulated by the kinase activity of IRAK4. Both IRAK4 and BTK inhibition reduced the TLR7-mediated differentiation of human memory B cells into plasmablasts. TLR7-dependent inflammatory responses were differentially regulated by IRAK4 and BTK by cell type: In pDCs, IRAK4 positively regulated NF-κB and MAPK signaling, whereas in B cells, NF-κB and MAPK pathways were regulated by both BTK and IRAK4. In the pristane-induced lupus mouse model, inhibition of IRAK4 reduced the expression of IRGs during disease onset. Mice engineered to express kinase-deficient IRAK4 were protected from both chemical (pristane-induced) and genetic (NZB/W_F1 hybrid) models of lupus development. Our findings suggest that kinase inhibitors of IRAK4 might be a therapeutic in patients with SLE.

Computation lithography: virtual reality and virtual virtuality.

Computation lithography is enabled by a combination of physical understanding, mathematical abstraction, and implementation simplification. An application in the virtual world of computation lithography can be a virtual reality or a virtual virtuality depending on its engineering sensibleness and technical feasibility. Examples under consideration include design-for-manufacturability and inverse lithography.

Capecitabine as adjuvant treatment for stage III colon cancer.

BACKGROUND: Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting. METHODS: We randomly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine (1004 patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983 patients) over a period of 24 weeks. The primary efficacy end point was at least equivalence in disease-free survival; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. RESULTS: Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis, P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20). Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin (P<0.001). CONCLUSIONS: Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer.

Initialization for robust inverse synthesis of phase-shifting masks in optical projection lithography.

The continuous shrinkage of minimum feature size in integrated circuit (IC) fabrication incurs more and more serious distortion in the optical projection lithography process, generating circuit patterns that deviate significantly from the desired ones. Conventional resolution enhancement techniques (RETs) are facing critical challenges in compensating such increasingly severe distortion. In this paper, we adopt the approach of inverse lithography in the mask design, which is a branch of design methodology to treat it as an inverse mathematical problem. We focus on using pixel-based algorithms to design alternating phase-shifting masks with minimally distorted output, with the goal that the patterns generated should have high contrast and low dose sensitivity. This is achieved with a dynamic-programming-based initialization scheme to pre-assign phases to the layout when alternating phase-shifting masks are used. Pattern fidelity and worst case slopes are shown to improve with this initialization scheme, which are important for robustness considerations.

Complexities and Challenges of Singapore Nurses Providing Postacute Home Care in Multicultural Communities: A Grounded Theory Study.

INTRODUCTION: Studies are needed to inform the preparation of community nurses to address patient behavioral and social factors contributing to unnecessary readmissions to hospital. This study uses nurses' input to understand challenges faced during home care, to derive a framework to address the challenges. METHODS: Semistructured interviews were conducted to saturation with 16 community nurses in Singapore. Interviews were transcribed verbatim and transcripts independently coded for emergent themes. Themes were interpreted using grounded theory. RESULTS: Seven major themes emerged from 16 interviews: Strained social relationships, complex care decision-making processes within families, communication barriers, patient's or caregiver neglect of health issues, building and maintaining trust, trial-and-error nature of work, and dealing with uncertainty. DISCUSSION: Community nurses identified uncertainty arising from complexities in social-relational, personal, and organizational factors as a central challenge. Nursing education should focus on navigating and managing uncertainty at the personal, patient, and family levels.

Regulation of appetite in lean and obese adolescents after exercise: role of acylated and desacyl ghrelin.

CONTEXT: Increased physical activity is an integral part of weight loss programs in adolescents. We hypothesized that exercise could affect appetite-regulating hormones and the subjective desire to eat, which could partly explain the poor success rate of the existing interventions. OBJECTIVE: The objective of this study was to investigate prospectively the effects of exercise on acylated ghrelin (AG) and desacyl ghrelin (DG) concentrations and on appetite. SETTING: The setting for this study was a tertiary care center. PARTICIPANTS: Normal-weight [NW; body mass index (mean +/- se), 20.7 +/- 0.5 kg/m2] and overweight (OW; body mass index, 32.4 +/- 1.7) male adolescents (n = 17/group, age 15.3 +/- 0.2 yr) were studied. INTERVENTION: Those studied participated in 5 consecutive days of aerobic exercise (1 h/d). MAIN OUTCOME: Changes in AG and DG concentrations and in appetite during a test meal were studied. RESULTS: Exercise did not significantly affect insulin sensitivity or body weight. Fasting total (AG and DG) ghrelin concentrations were lower in OW (600 +/- 33 pg/ml) compared with NW (764 +/- 33 pg/ml, P < 0.05) boys and were not affected by exercise. In contrast, there was a differential effect of exercise on both AG and DG (P