IMECE2003-41450 SIMULATION AND DESIGN AN E. COLI-BASED ROTARY MICROPUMP FOR USE IN MICROFLUIDIC SYSTEMS: INTEGRATION OF MICRO-NANO-BIO

ABSTRACT This paper presents the results of the computational fluid dynamic (CFD) modeling of viscous fluid flow in a novel cell motor actuated micropump. A cell motor is a bacterial flagellar cell tethered to a surface by a single flagellum, this flagellum acts as a pivot around which the cell body rotates. As a test case for investigation, the micropump consisted of two Escherichia coli cell motors tethered to the bottom of a microchannel with fixed dimensions. The CFD modeling of the micropump was performed using CFD-ACE + simulation software (CFD Research Corporation). The biological cell motor was modeled as an ellipse with constant rotational speed of 10 Hz clockwise. The results of this model demonstrated the effect of the biological cell motor placement within the microchannel, as well as the rotational phase between the two biological cell motors, on the volumetric flowrate. Pumping action was observed as the cell motor location was moved adjacent to the sidewall of the microchannel. The rates of fluid pumping were of the order of 11 pL/hr when the cell motors were rotating in phase and their placement was close to the sidewall of the microchannel. NOMENCLATURE Biological cell motor, computational fluid dynamics, E. coli, finite-volume, microchannel, microfluidic, micropump

Deeply conserved synteny resolves early events in vertebrate evolution

Although it is widely believed that early vertebrate evolution was shaped by ancient whole-genome duplications, the number, timing and mechanism of these events remain elusive. Here, we infer the history of vertebrates through genomic comparisons with a new chromosome-scale sequence of the invertebrate chordate amphioxus. We show how the karyotypes of amphioxus and diverse vertebrates are derived from 17 ancestral chordate linkage groups (and 19 ancestral bilaterian groups) by fusion, rearrangement and duplication. We resolve two distinct ancient duplications based on patterns of chromosomal conserved synteny. All extant vertebrates share the first duplication, which occurred in the mid/late Cambrian by autotetraploidization (that is, direct genome doubling). In contrast, the second duplication is found only in jawed vertebrates and occurred in the mid-late Ordovician by allotetraploidization (that is, genome duplication following interspecific hybridization) from two now-extinct progenitors. This complex genomic history parallels the diversification of vertebrate lineages in the fossil record

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Villoglandular Adenocarcinoma of the Uterine Cervix: An Analysis of 12 Clinical Cases

Background: Villoglandular adenocarcinoma (VGA) of the uterine cervix is a relatively rare subtype of endocervical adenocarcinomas that often occurs in early reproductive women. Methods: Clinical cases were retrospectively collected from the cancer registry systems at Mackay Memorial Hospital (Taipei, Taiwan). Clinical histories on the subjects were extracted directly from chart review of records of clinic visits. Results: The mean age of 12 subjects was 42 years, with 10 and 2 subjects clinically staged as IB1 (10 of 12) and IA2 (2 of 12), respectively, for the period between January 1, 1996, and December 31, 2007. Eleven subjects had classical Type III radical hysterectomy with or without bilateral salpingo-oophorectomy plus bilateral pelvic lymphadenectomy, and one received pelvic and para-aortic lymphadenectomy plus postoperative adjuvant treatment of weekly cisplatin concurrent with radiotherapy. Only one subject had confirmed pelvic lymph nodes metastases. Nine subjects had pure histologic type and others had mixed histologic type of VGA. Only one subject had a recurrence but was still alive. Most subjects were long-term survivors (greater than 5 years) (10 of 12). Conclusion: In conclusion, this study confirms the young age of subjects with VGA and reemphasizes the difficulties in the diagnosis of VGA. Because the current management strategy renders good tumor control in young subjects with early-stage VGA, we would suggest that similar treatment should be considered for elder subjects with this rare category of cervical malignancy. Our experience shows that the primary management of subjects with early-stage VGA (International Federation of Gynecology and Obstetrics Stages IA2 to IIA1) is classical Type III radical hysterectomy plus salpingo-oophorectomy with bilateral pelvic lymphadenectomy at MMH. We hope our 12-case experience may contribute to the clinical decision making for subjects with this disease

台灣節能標章認證制度擴散速率與影響因素之研究The Analysis of Diffusion Rates and Influence Factors of Energy Label in Taiwan

[[abstract]]近年來，溫室暖化的情形日趨嚴重，也逐漸迫害人類生存的環境，因此各國無不致力於降低能源消費以減少溫室氣體的排放。有鑑於此，政府已於2001年開始推動節能標章，積極輔導廠商改善電器產品的能源效率，以減少不必要的能源消費；另一方面，申請電器產品的節能標章也表示台灣在節約能源的成果邁向新的里程碑。為提升家電用品的能源使用效率，政府藉由制度面與法規面對市場上耗能之電器產品的能源使用效率進行規範，並提供節能標章之申請，藉此逐步提高我國耗能電器產品之能源效率。隨著節能政策的積極推行，節能標章申請的成效也逐一呈現，廠商也將會更積極投入於節能技術的創新，以達政府所設定之標準。為了貫徹降低能源消費的目標，節能標章申請推廣於所有電器產品上是必然的趨勢，因此本研究擬藉由擴散效果模型、組織學習效果模型與交互效果模型探討政府節能策推行的過程中，影響政策推動的關鍵因素，加速節能標章申請能普遍的應用於各種電器產品上，以達到順利及快速推廣節能標章申請的目的。 In recent years, greenhouse warming is growing and it gradually affects human living environment. Hence, every country in the world is committed to energy consumption reduction and the government started to promote the energy label since 2001. The energy label actively encourags firms to improve the energy efficiency and applies energy label in electrical products. This is a new milestone in Taiwan for promotion of energy saving and carbon reduction. In order to enhance the energy efficiency of household appliances, government regulates electrical equipment energy efficiency standards through law and system. By implementing the energy label system, it gradually increases the energy efficiency of energy-consuming products in Taiwan. With the promotion of energy saving and carbon reduction policies, the effects of energy label also present one by one. Through the promotion of energy label, manufacturers will be more actively involved in energy label technological innovation to achieve the standards set by the government. This will help government achieve the purpose of energy saving and carbon reduction. In order to achieve the reduction in energy consumption, it is an inevitable trend to promote energy label in most electrical products. Hence, this research is to explore the key factors that affect the policy implementation by studying the diffusion model, organizational learning model and interaction effect model. To achieve a smooth and rapid promotion of energy label system, we want to study the key factors that make energy label widely used in various electrical products and affect potential users to accept the policy