Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-objective Analysis of MAP-Elites Performance

In certain complex optimization tasks, it becomes necessary to use multiple measures to characterize the performance of different algorithms. This paper presents a method that combines ordinal effect sizes with Pareto dominance to analyze such cases. Since the method is ordinal, it can also generalize across different optimization tasks even when the performance measurements are differently scaled. Through a case study, we show that this method can discover and quantify relations that would be difficult to deduce using a conventional measure-by-measure analysis. This case study applies the method to the evolution of robot controller repertoires using the MAP-Elites algorithm. Here, we analyze the search performance across a large set of parametrizations; varying mutation size and operator type, as well as map resolution, across four different robot morphologies. We show that the average magnitude of mutations has a bigger effect on outcomes than their precise distributions.
A Phase I Clinical Trial of AZD1775 in Combination with Neoadjuvant Weekly Docetaxel and Cisplatin before Definitive Therapy in Head and Neck Squamous Cell Carcinoma

Purpose: The WEE1 tyrosine kinase regulates G2–M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy. Thus, a need arises to exploit the role of WEE1 inhibition in head and neck squamous cell carcinoma (HNSCC) mostly driven by tumor-suppressor loss. This completed phase I clinical trial represents the first published clinical experience using the WEE1 inhibitor, AZD1775, with cisplatin and docetaxel. Patients and Methods: We implemented an open-label phase I clinical trial using a 3+3 dose-escalation design for patients with stage III/IVB HNSCC with borderline-resectable or -unresectable disease, but who were candidates for definitive chemoradiation. Escalating AZD1775 was administered orally twice a day over 2.5 days on the first week, then in combination with fixed cisplatin (25 mg/m2) and docetaxel (35 mg/m2) for 3 additional weeks. The primary outcome measure was adverse events to establish MTD. Secondary measures included response rates, pharmacokinetics (PK), pharmacodynamics, and genomic data. Results: The MTD for AZD1775 was established at 150 mg orally twice per day for 2.5 days. RECISTv1.1 responses were seen in 5 of 10 patients; histologic adjustment revealed three additional responders. The only drug-limiting toxicity was grade 3 diarrhea. The PK C8hr target of 240 nmol/L was achieved on day 4 at all three doses tested. Pharmacodynamic analysis revealed a reduction in pY15-Cdk, and increases in γH2AX, CC3, and RPA32/RPA2 were noted in responders versus nonresponders. Conclusions: The triplet combination of AZD1775, cisplatin, and docetaxel is safe and tolerable. Preliminary results show promising antitumor efficacy in advanced HNSCC, meriting further investigation at the recommended phase II dose. Clin Cancer Res; 24(12); 2740–8. ©2018 AACR.
Characteristics of alpha males in Nepal gray langurs

In species with strong male‐male competition, access to females in multimale‐multifemale groups is usually regulated via a dominance hierarchy. The highest ranking (alpha) male often has priority of access and sires most offspring. The alpha male can change in three basic ways: (i) a recent immigrant or a resident challenges and becomes the new alpha; (ii) formation of a new group; (iii) succession—becoming alpha after higher ranking males have left. When, in a given primate population, the alpha male changes in different ways, two questions arise: (a) which is the most successful tactic and (b) do male attributes, such as age, aggressiveness or propensity to commit infanticide, affect the outcome? We examined these questions in the seasonally breeding Nepal gray langurs (Semnopithecus schistaceus) at Ramnagar, where new alpha males were either recent immigrants or residents. Success was measured as alpha tenure, residency duration, and the number of offspring sired (paternity exclusion based on DNA analysis, 28 infants). We documented 12 alpha‐male tenures across two multimale‐multifemale groups between 1991 and 1997. The predominant mode of change was the immigrant tactic. Age had no effect perhaps because alpha males were among the youngest adult males in their group. As expected, infanticidal males performed similarly to non‐infanticidal ones. Alpha tenure was highly variable and longer for immigrant alphas and hyper‐aggressive ones. However, none of the tactics or attributes examined resulted in significantly longer residencies or more offspring, likely because of the timing of immigrations and stochastic effects (i.e., the number of conceptions occurring per alpha tenure). The influence of female mate choice on male reproductive success requires further investigation. Furthermore, it remains to be examined why resident alpha males—with their presumed better knowledge of their opponents —performed so poorly. Am. J. Primatol. 79:e22437, 2017. © 2015 Wiley Periodicals, Inc.
Multiple Motor Learning Strategies in Visuomotor Rotation

Background When exposed to a continuous directional discrepancy between movements of a visible hand cursor and the actual hand (visuomotor rotation), subjects adapt their reaching movements so that the cursor is brought to the target. Abrupt removal of the discrepancy after training induces reaching error in the direction opposite to the original discrepancy, which is called an aftereffect. Previous studies have shown that training with gradually increasing visuomotor rotation results in a larger aftereffect than with a suddenly increasing one. Although the aftereffect difference implies a difference in the learning process, it is still unclear whether the learned visuomotor transformations are qualitatively different between the training conditions. Methodology/Principal Findings We examined the qualitative changes in the visuomotor transformation after the learning of the sudden and gradual visuomotor rotations. The learning of the sudden rotation led to a significant increase of the reaction time for arm movement initiation and then the reaching error decreased, indicating that the learning is associated with an increase of computational load in motor preparation (planning). In contrast, the learning of the gradual rotation did not change the reaction time but resulted in an increase of the gain of feedback control, suggesting that the online adjustment of the reaching contributes to the learning of the gradual rotation. When the online cursor feedback was eliminated during the learning of the gradual rotation, the reaction time increased, indicating that additional computations are involved in the learning of the gradual rotation. Conclusions/Significance The results suggest that the change in the motor planning and online feedback adjustment of the movement are involved in the learning of the visuomotor rotation. The contributions of those computations to the learning are flexibly modulated according to the visual environment. Such multiple learning strategies would be required for reaching adaptation within a short training period.
Association between Ocular Bacterial Carriage and Follicular Trachoma Following Mass Azithromycin Distribution in The Gambia

Background Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindess, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of follicular trachoma (TF) is not infected with C. trachomatis. A recent study in Tanzania suggested that other bacteria may play a role in the persistence of these clinical signs. Methodology/Principal Findings We examined associations between clinical signs of TF and ocular colonization with four pathogens commonly found in the nasopharnyx, three years after the initiation of mass azithromycin distribution. Children aged 0 to 5 years were randomly selected from 16 Gambian communitites. Both eyes of each child were examined and graded for trachoma according to the World Health Organization (WHO) simplified system. Two swabs were taken from the right eye: one swab was processed for polymerase chain reaction (PCR) using the Amplicor test for detection of C. trachomatis DNA and the second swab was processed by routine bacteriology to assay for the presence of viable Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Prevalence of TF was 6.2% (96/1538) while prevalence of ocular C. trachomatis infection was 1.0% (16/1538). After adjustment, increased odds of TF were observed in the presence of C. trachomatis (OR = 10.4, 95%CI 1.32–81.2, p = 0.03), S. pneumoniae (OR = 2.14, 95%CI 1.03–4.44, p = 0.04) and H. influenzae (OR = 4.72, 95% CI 1.53–14.5, p = 0.01). Conclusions/Significance Clinical signs of TF can persist in communities even when ocular C. trachomatis infection has been controlled through mass azithromycin distribution. In these settings, TF may be associated with ocular colonization with bacteria commonly carried in the nasopharnyx. This may affect the interpretation of impact surveys and the determinations of thresholds for discontinuing mass drug administration.
Alternative neural circuitry that might be impaired in the development of Alzheimer disease

It is well established that some individuals with normal cognitive capacity have abundant senile plaques in their brains. It has been proposed that those individuals are resilient or have compensation factors to prevent cognitive decline. In this comment, we explore an alternative mechanism through which cognitive capacity is maintained. This mechanism could involve the impairment of alternative neural circuitry. Also, the proportion of molecules such as Aβ or tau protein present in different areas of the brain could be important.
Factors associated with cholera in Kenya, 2008-2013

Introduction Kenya experienced widespread cholera outbreaks in 1997-1999 and 2007-2010. The re-emergence of cholera in Kenya in 2015 indicates that cholera remains a public health threat. Understanding past outbreaks is important for preventing future outbreaks. This study investigated the relationship between cholera occurrence in Kenya and various environmental and demographic factors related to water, sanitation, socio-economic status, education, urbanization and availability of health facilities during the time period 2008-2013. Methods The primary outcome analyzed was the number of cholera cases at the district level, obtained from the Kenya Ministry of Health's national cholera surveillance records. Values of independent variables were obtained from the 2009 Kenya Population and Housing Census and other national surveys. The data were analyzed using a zero-inflated negative binomial regression model. Results Multivariate analysis indicated that the risk of cholera was associated with open defecation, use of unimproved water sources, poverty headcount ratio and the number of health facilities per 100,000 population (p < 0.05). No statistically significant association was found between cholera occurrence and education, percentage of population living in urban areas or population density. Conclusion The Sustainable Development Goals and Kenya's blueprint for development, Kenya Vision 2030, call for access to sanitation facilities and clean water for all by 2030. Kenya has made important economic strides in recent years but continues to be affected by diseases like cholera that are associated with low socio-economic status. Further expansion of access to sanitation facilities and clean water is necessary for preventing cholera in Kenya.
Decreasing Burden of Malaria in Pregnancy in Malawian Women and Its Relationship to Use of Intermittent Preventive Therapy or Bed Nets

Background The World Health Organization recommends insecticidal bednets and intermittent preventive treatment to reduce malaria in pregnancy. Longitudinal data of malaria prevalence and pregnancy outcomes are valuable in gauging the impact of these antimalarial interventions. Methodology/Principal Findings We recruited 8,131 women delivering in a single Malawian hospital over 9 years. We recorded demographic data, antenatal prescription of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine and bed net use, and examined finger-prick blood for malaria parasites and hemoglobin concentration. In 4,712 women, we examined placental blood for malaria parasites and recorded the infant's birth weight. Peripheral and placental parasitemia prevalence declined from 23.5% to 5.0% and from 25.2% to 6.8% respectively. Smaller declines in prevalence of low birth weight and anemia were observed. Coverage of intermittent preventive treatment and bednets increased. Number of sulfadoxine-pyrimethamine doses received correlated inversely with placental parasitemia (Odds Ratio (95% CI): 0.79 (0.68, 0.91)), maternal anemia (0.81, (0.73, 0.90)) and low birth weight from 1997–2001 (0.63 (0.53, 0.75)), but not from 2002–2006. Bednet use protected from peripheral parasitemia (0.47, (0.37, 0.60)) and placental parasitemia (0.41, (0.31, 0.54)) and low birth weight (0.75 (0.59, 0.95)) but not anemia throughout the study. Compared to women without nets who did not receive 2-dose sulfadoxine-pyrimethamine, women using nets and receiving 2-dose sulfadoxine-pyrimethamine were less likely to have parasitemia or low birth weight babies. Women receiving 2-dose sulfadoxine-pyrimethamine alone had little evidence of protection whereas bednets alone gave intermediate protection. Conclusions/Significance Increased bednet coverage explains changes in parasitemia and birth weight among pregnant women better than sulfadoxine-pyrimethamine use. High bed net coverage, and sulfadoxine-pyrimethamine resistance, may be contributing to its apparent loss of effectiveness.
Maintaining Formation of Multiple Robotic Wheelchairs for Smooth Communication

To meet the demands of an aging society, research on intelligent/robotic wheelchairs have been receiving a lot of attention. In elderly care facilities, care workers are required to communicate with the elderly in order to maintain both their mental and physical health. While this is regarded as important, having a conversation with someone on a wheelchair while pushing it from behind in a traditional setting would interfere with their smooth and natural conversation. So we are developing a robotic wheelchair system which allows companions and wheelchair users to move in a natural formation. This paper reports on an investigation to learn the patterns of human behavior when the wheelchair users and their companions communicate while walking together. The ethnographic observation reveals a natural formation of positioning for both companions and wheelchair users. Based on this investigation, we propose a multiple robotic wheelchair system which can maintain desirable formations for communication between wheelchairs.
A Gaze-Assisted Multimodal Approach to Rich and Accessible Human-Computer Interaction

Recent advancements in eye tracking technology are driving the adoption of gaze-assisted interaction as a rich and accessible human-computer interaction paradigm. Gaze-assisted interaction serves as a contextual, non-invasive, and explicit control method for users without disabilities; for users with motor or speech impairments, text entry by gaze serves as the primary means of communication. Despite significant advantages, gaze-assisted interaction is still not widely accepted because of its inherent limitations: 1) Midas touch, 2) low accuracy for mouse-like interactions, 3) need for repeated calibration, 4) visual fatigue with prolonged usage, 5) lower gaze typing speed, and so on. This dissertation research proposes a gaze-assisted, multimodal, interaction paradigm, and related frameworks and their applications that effectively enable gaze-assisted interactions while addressing many of the current limitations. In this regard, we present four systems that leverage gaze-assisted interaction: 1) a gaze- and foot-operated system for precise point-and-click interactions, 2) a dwell-free, foot-operated gaze typing system. 3) a gaze gesture-based authentication system, and 4) a gaze gesture-based interaction toolkit. In addition, we also present the goals to be achieved, technical approach, and overall contributions of this dissertation research.
A 0.3-to-1.2V frequency-scalable fractional-N ADPLL with a speculative dual-referenced interpolating TDC

Power management with dynamic frequency control has been a key feature in battery-operated systems. It effectively reduces energy consumption by the microcontroller in mobile systems towards meeting ultra-low-power constraints for implantable system-on-a-chip wireless nodes by optimal profiling of voltage and frequency according to the operating modes and tasks. The essential circuit block for such applications is the phase-locked loop (PLL), supporting a wide frequency lock range scaled along with the supply voltage [1, 2]. Traditional design approaches of analog PLLs, however, are not suited for wide supply voltage operation since they suffer from degraded accuracy when subject to a reduction in supply headroom. On the other hand, all-digital PLL implementations hold inherent benefits of robustness, small size and programmability with strong immunity to process and supply variations. While a number of integer-N digital PLLs have successfully demonstrated wide frequency lock ranges scaled with supply voltage, there have been few reported works on fractional-N frequency generation. Fractional-N frequency generation imposes additional requirements on the time-to-digital converter (TDC), such as high linearity, a wide conversion range with a fine resolution, and an automatic gain calibration. When it comes to automated synthesis of a digital PLL, such requirements are an even greater challenge to be overcome. This paper presents a frequency and voltage-scalable fractional-N digital PLL mostly synthesized from a register-transfer-level (RTL) behavioral description. By speculating a time region for conversion, the TDC efficiently achieves a fine resolution with a dual-referenced interpolation [3]. The PLL, implemented in 0.0043mm2 in 28nm CMOS, achieves a wide frequency lock range operating at a supply voltage from 0.3–1.2V without any calibration or tuning.
Elevated miR-499 Levels Blunt the Cardiac Stress Response

Background The heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle. Methodology/Principal Findings We assessed miR-499 expression in human tissue to confirm its potential relevance to human cardiac gene regulation. Using a transgenic mouse model, we found that elevated miR-499 levels caused cellular hypertrophy and cardiac dysfunction in a dose-dependent manner. Global gene expression profiling revealed altered levels of the immediate early stress response genes (Egr1, Egr2 and Fos), ß-myosin heavy chain (Myh7), and skeletal muscle actin (Acta1). We verified the effect of miR-499 on the immediate early response genes by miR-499 gain- and loss-of-function in vitro. Consistent with a role for miR-499 in blunting the response to cardiac stress, asymptomatic miR-499-expressing mice had an impaired response to pressure overload and accentuated cardiac dysfunction. Conclusions Elevated miR-499 levels affect cardiac gene expression and predispose to cardiac stress-induced dysfunction. miR-499 may titrate the cardiac response to stress in part by regulating the immediate early gene response.
Diagnosis and management of aortic graft infection.

This report summarizes the currently available methods of diagnosing and treating aortic graft infections. These infections tend to present in subtle ways; therefore, no single diagnostic test is appropriate for all patients. Available imaging techniques have a wide spectrum of sensitivity and specificity. Complementary tests may be necessary to confirm the diagnosis, determine the extent of infection, and assist with operative planning. Once localized, the infectious organism should be cultured. Treatment should be highly individualized and determined by the virulence of the infectious organism, the extent of infection, and the medical status of the patient. Whereas graft excision and extra-anatomic revascularization remains the "gold standard" for treatment of aortic graft infection, the use of in situ replacement with autogenous vein has been shown to be an excellent alternative. In very limited circumstances, in situ replacement with allograft or rifampin-bonded prosthesis may be acceptable.
Deep and Clear Optical Imaging of Thick Inhomogeneous Samples

Inhomogeneity in thick biological specimens results in poor imaging by light microscopy, which deteriorates as the focal plane moves deeper into the specimen. Here, we have combined selective plane illumination microscopy (SPIM) with wavefront sensor adaptive optics (wao). Our waoSPIM is based on a direct wavefront measure using a Hartmann-Shack wavefront sensor and fluorescent beads as point source emitters. We demonstrate the use of this waoSPIM method to correct distortions in three-dimensional biological imaging and to improve the quality of images from deep within thick inhomogeneous samples.
Prescription of high-risk medications among patients with chronic kidney disease: a cross-sectional study from the Washington, Wyoming, Alaska, Montana and Idaho region Practice and Research Network

Background Patients with chronic kidney disease (CKD) are at high risk for adverse drug events related to medication dosing errors and prescriptions for relatively contraindicated medications, such as non-steroidal anti-inflammatory drugs (NSAIDs). Objectives To examine the scope of and variation in prescribing relatively contraindicated medications and medications above the recommended dose levels among patients with stage III/IV CKD in primary care practice. Methods This is a cross-sectional descriptive study that used structured electronic health record data. The study participants were patients aged 18 years and older from three primary care clinics in a practice-based research network. Number/proportion of adult patients with stage III/IV CKD; proportion of these patients with at least one NSAID or other relatively contraindicated medication prescribed over 2 years. Results Of the 7586 eligible adult patients, 4.9% had stage III/IV CKD; 46.6% of these 373 patients with stage III/IV CKD were prescribed at least one relatively contraindicated drug (acarbose, chlorpropamide, glyburide, nitrofurantoin or any NSAID) during the 2-year study period; and 34.0% of patients with stage III/IV CKD were prescribed NSAIDs. Conclusions Primary care patients with stage III/IV CKD were frequently prescribed or had documented use of relatively contraindicated drugs and thus were at risk of adverse drug events. Given the significant number of individuals with CKD in the USA, research that examines rates of adverse events related to these prescriptions and that tests primary care-based interventions to decrease inappropriate prescribing of relatively contraindicated medications to these patients is needed.