Optimal design of a bistable switch

Determining optimally designed structures is important for diverse fields of science and engineering. Here we describe a procedure for calculating the optimal design of a switch and apply the method to a bistable microelectromechanical system relay switch. The approach focuses on characterizing the unstable transition state connecting the two stable equilibria to control the force displacements. Small modifications in component shape lead to a substantial improvement in device operation. Fabrication of the optimized devices confirms the predictions.     

Magnetic sphincter augmentation: Optimal patient selection and referral care pathways

Outcomes associated with magnetic sphincter augmentation(MSA) in patients with gastroesophageal reflux disease(GERD) have been reported, however the optimal population for MSA and the related patient care pathways have not been summarized. This Minireview presents evidence that describes the optimal patient population for MSA, delineates diagnostics to identify these patients, and outlines opportunities for improving GERD patient care pathways. Relevant publications from MEDLINE/EMBASE and guidelines were identified from2000-2018. Clinical experts contextualized the evidence based on clinical experience. The optimal MSA population may be the 2.2-2.4% of GERD patients who, despite optimal medical management, continue experiencing symptoms of heartburn and/or uncontrolled regurgitation, have abnormal p H, and have intact esophageal function as determined by high resolution manometry. Diagnostic work-ups include ambulatory p H monitoring, high-resolution manometry,barium swallow, and esophagogastroduodenoscopy. GERD patients may present with a range of typical or atypical symptoms. In addition to primary care providers(PCPs) and gastroenterologists(GIs), other specialties involved may include otolaryngologists, allergists, pulmonologists, among others. Objective diagnostic testing is required to ascertain surgical necessity for GERD. Current referral pathways for GERD management are suboptimal. Opportunities exist for enabling patients, PCPs, GIs, and surgeons to act as a team in developing evidence-based optimal care plans.     

Living arrangements and sources of caregiving

This study examined both the prevalence of different types of caregivers (in terms of the relation to the individual), and whether living with someone is more important for caregiving than the relation of an elder to an individual. Caregiving is examined in terms of IADL and emotional support. Analyses are conducted using three separate random samples of those who are married and living with a spouse, those who live alone, and those who live with nonspousal others in Winnipeg, Manitoba, Canada. The results confirm previous research pointing out that married people tend to receive assistance from their spouse. Among nonmarrieds, children are named most frequently as the primary caregiver. After children, however, those who live alone tend to receive assistance from friends, and those who live with nonspousal others receive assistance from siblings. The data further document the importance of the structural characteristic of living with someone, rather than marital status, for assistance with IADL.     

Optimal protocol selection for cardiopulmonary exercise testing in severe COPD

BACKGROUND: The current recommendations of 8 to 12 min for the optimal targeted duration of symptom-limited maximal cardiopulmonary exercise testing (CPET) to attain maximal oxygen consumption are based on results from healthy individuals and may not be applicable to patients with severe COPD. We aimed to determine the optimal duration for a CPET to attain the peak oxygen consumption (VO2peak) in a group of patients with severe COPD using different carefully conducted workload protocols. METHODS: We studied 11 subjects with severe COPD (mean FEV1, 32% predicted; 95% confidence interval [CI], 27 to 38% predicted). They completed four incremental, symptom-limited exercise tests on a cycle ergometer using four protocols (4, 8, and 16 W/min continuous ramp protocols, and 8 W/min step protocol) using a randomized double-blind design. RESULTS: The mean duration of these 44 tests was 6.3 min (95% CI, 5.0 to 9.0 min). The duration of the exercise tests differed significantly for the protocols used, as follows: 16-W ramp protocol, 4.0 min (95% CI, 3.0 to 5.1 min); 8-W ramp protocol, 6.6 min (95% CI, 5.0 to 9.0 min); 8-W step protocol, 6.0 min (95% CI, 4.0 to 8.0 min); and 4-W ramp protocol, 8.7 min (95% CI, 4.4 to 13.0 min; p<0.001). The maximal workload significantly increased as the ramp slope increased from 4 to 8 to 16 W/min (maximal workload, 35.6 vs 50.7 vs 64.3 W, respectively; p<0.001). Maximal minute ventilation, heart rate, Borg ratings, and VO2 peak, were not different among the four protocols. No differences were found between the ramp and step protocols. CONCLUSIONS: In patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease stages III-IV), a targeted duration of 5 to 9 min for a CPET appears to be more appropriate than the 8 to 12 min proposed in the current guidelines. Maximal workload, in contrast to VO2peak, is highly dependent on the ramp incrementation rate.     

Optimal sequence selection in proteins of known structure by simulated evolution.

Rational design of protein structure requires the identification of optimal sequences to carry out a particular function within a given backbone structure. A general solution to this problem requires that a potential function describing the energy of the system as a function of its atomic coordinates be minimized simultaneously over all available sequences and their three-dimensional atomic configurations. Here we present a method that explicitly minimizes a semiempirical potential function simultaneously in these two spaces, using a simulated annealing approach. The method takes the fixed three-dimensional coordinates of a protein backbone and stochastically generates possible sequences through the introduction of random mutations. The corresponding three-dimensional coordinates are constructed for each sequence by "redecorating" the backbone coordinates of the original structure with the corresponding side chains. These are then allowed to vary in their structure by random rotations around free torsional angles to generate a stochastic walk in configurational space. We have named this method protein simulated evolution, because, in loose analogy with natural selection, it randomly selects for allowed solutions in the sequence of a protein subject to the "selective pressure" of a potential function. Energies predicted by this method for sequences of a small group of residues in the hydrophobic core of the phage lambda cI repressor correlate well with experimentally determined biological activities. This "genetic selection by computer" approach has potential applications in protein engineering, rational protein design, and structure-based drug discovery.     

Age-related glucometer design and selection: tools and principles for optimal solutions

Special attention must be given to glucometer design, selection, and training for older adults with diabetes. The field of human factors provides insight into the special needs of older adults along with principles of design and instruction to apply to current and future glucometer systems. Necessary tools for designers and physicians include person analysis, user testing, and adherence to best practice guidelines. It is important to note that as glucometer systems change, new usability problems may arise as prior issues are resolved. However, some problems may be avoided prior to system production by using the theoretical background and guidelines provided by human factors specialists.     

Higher criticism thresholding: Optimal feature selection when useful features are rare and weak

In important application fields today-genomics and proteomics are examples-selecting a small subset of useful features is crucial for success of Linear Classification Analysis. We study feature selection by thresholding of feature Z-scores and introduce a principle of threshold selection, based on the notion of higher criticism (HC). For i = 1, 2, ..., p, let pi(i) denote the two-sided P-value associated with the ith feature Z-score and pi((i)) denote the ith order statistic of the collection of P-values. The HC threshold is the absolute Z-score corresponding to the P-value maximizing the HC objective (i/p - pi((i)))/sqrt{i/p(1-i/p)}. We consider a rare/weak (RW) feature model, where the fraction of useful features is small and the useful features are each too weak to be of much use on their own. HC thresholding (HCT) has interesting behavior in this setting, with an intimate link between maximizing the HC objective and minimizing the error rate of the designed classifier, and very different behavior from popular threshold selection procedures such as false discovery rate thresholding (FDRT). In the most challenging RW settings, HCT uses an unconventionally low threshold; this keeps the missed-feature detection rate under better control than FDRT and yields a classifier with improved misclassification performance. Replacing cross-validated threshold selection in the popular Shrunken Centroid classifier with the computationally less expensive and simpler HCT reduces the variance of the selected threshold and the error rate of the constructed classifier. Results on standard real datasets and in asymptotic theory confirm the advantages of HCT.     

Optimization of product in dynamic design space and selection through the arc-elasticity concept

In the industrial design process, “trial-and-error” loops are usually used between design departments and simulation departments, to design and validate a candidate solution. Such a solution is defined by instantiated design variables, characterizing the main parameters of the product. This paper proposes to replace the trial-and-error process by an optimization method; two bottlenecks were identified: the importance of the initial design solution which has already engaged delays and costs, and the formalization of designers preferences to select high-performance solutions. To take into account the initial solution, a strategy is proposed to explore the global design space (which represents all the candidate solutions) starting from the initial one, and using a hierarchical organization of the design variables. Then, the Observation–Interpretation–Aggregation method is used first to formalize designer knowledge related to the product to design and then to rank every design solution using a single performance value. Moreover, the concept of arc-elasticity is used to qualify a solution through its neighborhood, and to characterize technological breakthroughs, compared to the initial solution. This method is discussed and illustrated through the design of an aeronautical riveted assembly.     

Functional capacity and living arrangements of unmarried elderly persons

This analysis employed the 1986 Longitudinal Study of Aging (LSOA) to examine the impact of functional capacity, gender, race and ethnicity, and various socioeconomic characteristics on changes in living arrangements among unmarried elderly persons over a two-year period. The results reveal that a decline in functional capacity greatly increases the likelihood that an elderly person will move in with others or become institutionalized. Nonetheless, even when they experience significant declines in health, most single elderly persons who were living alone at the initial interview continued to live alone two years later. Multivariate analyses show that women who suffer declines in functional capacity are somewhat less likely than men who experience declines to live alone at Time two. In contrast, Blacks who suffer declines are more likely than Whites who experience declines to continue living alone at follow-up.     

Platelet transfusion therapy. Optimal donor selection with a combination of lymphocytotoxicity and platelet fluorescence tests.

Although the value of HLA matching for the selection of platelet donors for patients refractory to random platelets is beyond doubt, even perfectly matched combinations sometimes fail to give a satisfactory transfusion response. With HLA typing and negative lymphocytotoxicity crossmatches, 35% of the platelet transfusions administered to 15 patients gave disappointing results (29 of 82). Additional crossmatching with the newly developed platelet fluorescence test described in this paper reduced the unexpected transfusion failures to 7% (6 of 82). Five of these failures were observed in one patient. The target of the antibodies detected with this platelet fluorescence test is not yet fully specified. It seems probable that both HLA and platelet-specific non-HLA antibodies were detected. No correlation of the results of platelet transfusions with the presence or absence of leukoagglutinating antibodies was found.     

Living arrangements of elderly Japanese and attitudes toward inheritance.

Using data from the 1988 Mainichi Newspaper/Nihon University National Family Survey, we analyzed the living arrangements and attitudes toward inheritance of Japanese aged 60 and over. Logit analysis indicates that living arrangements are influenced by gender, age, marital status, education, urban residence, and number of living children. Log-linear modeling of inheritance attitudes shows that living with married children, lower educational attainment, and living in a traditionally agricultural area are associated with favoring bequests to eldest sons, as opposed to bequests to all children equally or to whoever takes care of the elderly person. The results are consistent with modernization theory of gerontology and convergence theory of family sociology in that elderly persons with more "modern" characteristics are more likely to depart from prewar ideals of living with married children and preferring bequests to eldest sons only.     

Living arrangements and socio-demographic conditions of older adults in Cambodia

Since the takeover of Cambodia by the Khmer Rouge in 1975, the socialconditions within the country have been understudied. Only recently hasdependable socio-demographic data become available. We use some thesedata to examine living arrangements and other socio-demographicconditions among Cambodia's older population. We compare results to thoserecently found in Thailand and Vietnam, two neighboring countries, inorder to place Cambodia within a regional context. On balance, livingarrangements in Cambodia are similar to those in neighboring countries.Older adults are likely to be living with a child and in a variety of diversearrangements involving different family members. We attempt to get atgender preference for coresident children indirectly by adjusting livingarrangement patterns for Cambodia's unique sex and marital statusstructure. We find a predominance of elders living with never marriedchildren of either sex and a slight daughter preference. Older adults inCambodia may face particular challenges due to the influences of the pastdecades of instability and violence. We conclude our paper with adiscussion of how future research might assist in developing a nationalpolicy for older adults.     

组织多普勒指导心脏再同步治疗中左心室电极导线的植入

心脏再同步化治疗（CRT）作为慢性充血性心力衰竭治疗的有效方法之一，已逐渐被人们接受，在多数病人中，它能改善临床症状，逆转或终止慢性心脏重构。然而，仍有约20％～30％的患者起搏后症状未改善甚至恶化。究其原因可能与患者入选不合适以及左心室电极导线位置不恰当有关，但目前国内外对于如何指导左心室电极导线的放置还没有理想的方法。我们运用组织多普勒技术，在术前直接测量心室机械不同步性，识别室壁运动最延迟的部位及其程度，指导术中左心室起搏电极导线的放置，取得了较好的临床效果。     

组织多普勒指导心脏再同步化治疗中左室电极导线的植入

目的运用组织多普勒技术指导心脏再同步化治疗(cardiac resynchronization therapy,CRT)中左室电极导线的植入并评价CRT短期疗效.方法选择拟行CRT的慢性充血性心力衰竭患者7例,起搏前行常规超声心动图和组织多普勒检查,计算LVEF、Tei指数、左右心室间不同步参数(T1-T2),QRS距左室各节段收缩峰值时间的标准差(Ts-SD),经心率校正的Ts-SD(Ts-SDC),并根据组织同步显像图(TSI)的色彩计算TSI指数.结合组织速度显像、组织追踪显像、组织同步显像3种方法判断左室延迟收缩的部位和程度,根据延迟的部位选择靶静脉及导线植入的深度,比较起搏前后各参数的变化.结果起搏前左室延迟收缩的部位存在较大的个体差异.在组织多普勒指导下,2例选择了左室后静脉,2例选择了左室侧静脉,3例选择了左室侧后静脉.起搏后7～10天,所有患者左心功能改善LVEF由起搏前的(27.3±7.4)%增高至(40.7±8.9)%(P＜0.01),Tei指数由1.23±0.70降低至0.83±0.33(P＜0.05),且心率较起搏前减慢(P＜0.05);左心室内收缩不同步改善TSI指数由起搏前的2.03±0.22降低至1.62±0.33(P＜0.05),Ts-SDC由191.39±47.35降低至119.45±62.02(P＜0.05);左右心室间收缩不同步改善T1-T2由起搏前(49.14±26.82)ms降低至(15.43±11.30)ms(P＜0.05);左房内径起搏后缩小(P＜0.01).结论组织多普勒可用于识别心室机械不同步的程度和部位,对于指导CRT中左室电极导线的植入和疗效的评价具有重要的实用价值.