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Fundamental materials properties are determined by electrons under the potential energy from the nuclei, the electron mass, and their mutual repulsion. The variable from material to material is the ion potential. The logical procedure of computing electronic properties is to go from the potential to the electron distribution. This enables practical computation of the material properties ranging from atoms and molecules to solids. This method has blossomed due to the effort of numerous people. The concept is analogous to changing prediction of human population distribution from the landscape of hills and dales to determination of the landscape from a population distribution. In atomic systems, quantum quirkiness allows this switch, but dictates that it is only one slice in the tomography of the quantum state. The author shares his experience in the development from this slice, but hews close to the powerful concept of switching the landscape with the population.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
In recent years, men who have sex with men (MSM) constitute a major group of HIV transmission in China. High primary drug-resistance (PDR) rate in MSM also represents a serious challenge for the Chinese antiretroviral therapy (ART) program. To assess the efficiency of ART in controlling HIV/AIDS infection among MSM, we developed a compartmental model for the annually reported HIV/AIDS MSM from 2007 to 2019 in the Zhejiang Province of China. R0 was 2.3946 (95% CI (2.2961–2.4881)). We predict that 90% of diagnosed HIV/AIDS individuals will have received treatment till 2020, while the proportion of the diagnosed remains as low as 40%. Even when the proportion of the diagnosed reaches 90%, R0 is still larger than the level of AIDS epidemic elimination. ART can effectively control the spread of HIV, even in the presence of drug resistance. The 90-90-90 strategy alone may not eliminate the HIV epidemic in Chinese MSM. Behavioural and biologic interventions are the most effective interventions to control the HIV/AIDS epidemic among MSM.
Three-dimensional cultures have exciting potential to mimic aspects of healthy and diseased brain tissue to examine the role of physiological conditions on neural biomarkers, as well as disease onset and progression. Hypoxia is associated with oxidative stress, mitochondrial damage, and inflammation, key processes potentially involved in Alzheimer's and multiple sclerosis. We describe the use of an enzymatically-crosslinkable gelatin hydrogel system within a microfluidic device to explore the effects of hypoxia-induced oxidative stress on rat neuroglia, human astrocyte reactivity, and myelin production. This versatile platform offers new possibilities for drug discovery and modeling disease progression.
Adolescents have been largely neglected from tuberculosis control efforts. In low- to medium burden settings much of the tuberculosis burden in this age group occurs from school outbreaks. We report on a large tuberculosis outbreak in adolescents from a boarding high school in Jiangsu Province, China. From March to June 2018, a tuberculosis outbreak occurred in a boarding high school. We conducted an outbreak investigation involving clinical diagnostic tests and molecular analysis to determine the outbreak origin. Cases were detected through symptom screening, tuberculin skin testing (TST), chest radiography, sputum smear, solid sputum culture and GeneXpert MTB/RIF. Mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) genotyping and spoligotyping methods were performed on Mycobacterium tuberculosis (M. tuberculosis) isolates to identify the outbreak origin. A total of 845 students and 131 teachers/staff attended a TST screening for tuberculosis infection. The prevalence of elevated tuberculin reactions at ≥5, ≥10 and ≥15 mm was 12.19% (119/976), 6.35% (62/976) and 3.28% (32/976), respectively. Radiographic abnormalities were present in 5.73% (56 of 976) individuals, 40 students and 16 teachers/staff. Of these, 12 students were diagnosed with confirmed tuberculosis. In total, 14 students (two index cases and 12 confirmed cases) were diagnosed and reported in the tuberculosis outbreak, an attack rate of 1.7% (14/847) among students (two index cases and 845 screened students). Results from MIRU-VNTR typing and spoligotyping analyses demonstrated that three M. tuberculosis strains belong to the Beijing family with corresponding MIRU-VNTR alleles. This school-based tuberculosis outbreak among adolescents demonstrates that transmission among individuals in this age group is common and must be prioritised. It suggests that identifying and timely diagnosis of smear-positive cases, especially in the early phase of outbreaks, is the key to preventing further spread among close contacts.
Background: To evaluate efficacy, safety, and tolerability of ubrogepant for acute treatment of migraine attacks. Methods: Multicenter, double-blind, phase 3 study (NCT02867709). Randomized patients (1:1:1, placebo or ubrogepant 25mg or 50mg) had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints (2 hours post initial dose): headache pain freedom and absence of most bothersome migraine-associated symptom (MBS). Secondary endpoints: pain relief, sustained pain relief, sustained pain freedom, and absence of migraine-associated symptoms. Results: 1686 patients were randomized (safety population: n=1465; mITT population: n=1355). Mean age: 41 years; white: 81%; female: 89%. Significantly greater proportions of ubrogepant- than placebo-treated patients achieved 2-hour pain freedom (placebo: 14.3%; 25mg: 20.7%, adjusted P=0.0285; 50mg: 21.8%, adjusted P=0.0129) and absence of MBS for 50mg (placebo: 27.4%; 50mg: 38.9%, adjusted P=0.0129). Secondary endpoints (except absence of nausea at 2h) met statistical significance versus placebo for ubrogepant 50mg. Absence of MBS and secondary outcomes were not significant for 25mg after multiplicity adjustment. Ubrogepant’s and placebo’s AE profiles were similar. Conclusions: Co-primary endpoints were met for ubrogepant 50mg. Ubrogepant 25mg was significantly superior to placebo for 2h pain freedom. Ubrogepant was well tolerated. Results support the efficacy, tolerability, and safety of ubrogepant for acute treatment of migraine attacks.
Background: To evaluate efficacy, safety, and tolerability of ubrogepant, an oral CGRP receptor antagonist, for acute treatment of a single migraine attack. Methods: Multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack, phase 3 study (NCT02828020). Patients randomized 1:1:1 to placebo, ubrogepant 50mg, or ubrogepant 100mg had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints: pain freedom 2 hours post initial dose and absence of most bothersome migraine-associated symptom (MBS). Results: 1672 patients were randomized (safety population: n=1436; mITT population: n=1327). Mean age: 40.7 years; white (82.4%); female (87.5%). A significantly greater percentage of ubrogepant- than placebo-treated patients achieved pain freedom 2 hours post initial dose (50mg: 19.2%, adjusted P=0.0023; 100mg: 21.2%, adjusted P=0.0003; placebo: 11.8%). A significantly greater percentage of ubrogepant patients achieved absence of MBS (50mg: 38.6%, adjusted P=0.0023, 100mg: 37.7%, adjusted P=0.0023; placebo: 27.8%). The adverse event (AE) profile of ubrogepant was similar to placebo. The most common AEs (incidence ≥2% in any treatment group) within 48 hours of initial or optional second dose were nausea, somnolence, and dry mouth (all with incidence <5%). Conclusions: Both co-primary endpoints were met, with clinically meaningful effects on migraine headache pain and MBS. Ubrogepant was well tolerated, with no identified safety concerns.
To compare the epidemiologic features (e.g. settings and transmission mode) and patient clinical characteristics associated with outbreaks of different norovirus (Nov) strains, we retrospectively analysed data of Nov outbreaks occurring in Guangzhou, China from 2012 to 2018. The results suggested that outbreaks of Nov GII.2, GII.17 and GII.4 Sydney exhibited different outbreak settings, transmission modes and symptoms. GII.2 outbreaks mainly occurred in kindergartens, elementary and high schools and were transmitted mainly through person-to-person contact. By contrast, GII.4 Sydney outbreaks frequently occurred in colleges and were primarily associated with foodborne transmission. Cases from GII.2 and GII.17 outbreaks reported vomiting more frequently than those from outbreaks associated with GII.4 Sydney.
A viscous damping model is proposed based on a simplified equation of fluid motion in a moonpool or the narrow gap formed by two fixed boxes. The model takes into account the damping induced by both flow separation and wall friction through two damping coefficients, namely, the local and friction loss coefficients. The local loss coefficient is determined through specifically designed physical model tests in this work, and the friction loss coefficient is estimated through an empirical formula found in the literature. The viscous damping model is implemented in the dynamic free-surface boundary condition in the gap of a modified potential flow model. The modified potential flow model is then applied to simulate the wave-induced fluid responses in a narrow gap formed by two fixed boxes and in a moonpool for which experimental data are available. The modified potential flow model with the proposed viscous damping model works well in capturing both the resonant amplitude and frequency under a wide range of damping conditions.
Patient memory for treatment contents is defined as memory for the ideas, concepts, skills, and/or insights (termed treatment points) that the therapist thinks are important for the patient to remember and implement as a part of therapy. This article reviews key findings on patient memory for treatment contents, describes the development and evaluation of the Memory Support Intervention (MSI), and outlines future directions for research. Patient memory for treatment contents is poor, and worse memory is associated with worse treatment outcome. The MSI is composed of eight memory support strategies that therapists incorporate frequently alongside treatment points delivered during treatment-as-usual. Training therapists to deliver the MSI may yield better treatment outcomes by enhancing patient memory for treatment contents. Future research is needed to understand how to best measure patient memory for treatment contents, and the mediators, moderators, and dissemination potential of the MSI.
Dietary supplementation with the organic chromium (Cr) has been shown to positively affect the immune function of poultry. However, to our knowledge, no experiment has been done to directly compare the impacts of Cr chloride and chromium picolinate (CrPic) on the immune responses of broilers vaccinated with Avian Influenza (AI) virus vaccine. Therefore, the present experiment was conducted to investigate the effects of supplemental Cr sources (Cr chloride and CrPic) and levels on the growth performance and immune responses of broilers vaccinated with AI virus vaccine so as to provide an effective nutritional strategy for improving immune function of broilers. A total of 432 1-day (d)-old male broiler chicks were used in a 1 plus 2×4 design. Chickens were given either a diet without Cr supplementation (control) or diets supplemented with 0.4, 0.8, 1.6, or 3.2 mg Cr/kg as either Cr chloride or CrPic for 42 d. Compared to the control, dietary Cr supplementation had no effect (P>0.05) on average daily gain, average daily feed intake and gain : feed of broilers during the starter and grower phases, but increased (P<0.05) the relative weights of bursa of fabricius on d 21 and thymus, spleen, or bursa of fabricius on d 42, serum antibody titers against AI virus on d 21, 28, 35 and 42, blood T-lymphocyte transformation rate on d 28 and 42, blood T-lymphocyte percentage on d 42, and serum interleukin-2 contents on d 28. Broilers fed the diets supplemented with the inorganic Cr chloride had higher (P<0.05) weights of thymus, spleen and bursa of fabricius than those fed the diets supplemented with the CrPic on d 42. In addition, broilers fed the diets supplemented with the CrPic had higher (P<0.05) antibody titers against AI virus than those fed the diets supplemented with the inorganic Cr chloride on d 21 and 35. These results indicate that dietary Cr supplementation improved immune responses of broilers vaccinated with AI virus, and the inorganic Cr chloride was more effective than the CrPic in increasing the relative weights of lymphoid organs, however, the CrPic was more effective than the inorganic Cr chloride in enhancing the serum antibody titer against AI virus.
Focused electron beam-induced deposition (FEBID) is capable of producing metal-containing nanostructures with lateral resolution on the sub-nanometer scale. Practical application of this nanofabrication technique has been hindered by ligand-derived contamination from precursors developed for thermal deposition methods. Mechanistic insight into FEBID through surface science studies and gas-phase electron–molecule interactions has begun to enable the design of custom FEBID precursors. These studies have shown that precursors designed to decompose under electron irradiation can produce high-purity FEBID deposits. Herein, we highlight the progress in FEBID precursor development with several examples that incorporate this mechanism-based design approach.
Litter size has a great impact on the profit of swine producers. Uterine development is an important determinant of reproduction efficiency and could hence affect litter size. Chinese Erhualian pig is one of the most prolific breeds in the world, even though large phenotypic variation in litter size was observed within Erhualian sows. To dissect the genetic basis of the phenotypic variation, we herein conducted genome-wide association studies for total number born and number born alive (NBA) of Erhualian sows. In total, one significant single nucleotide polymorphism (SNP) (P<1.78e−06) and 11 suggestive SNPs (P<3.57e−05) were identified on 10 chromosomes, confirming seven previously reported quantitative trait loci (QTL) and uncovering six QTL for litter size or uterus length. One locus on Sus scrofa chromosome (SSC) 13 (79.28 to 90.43 Mb) harbored a cluster of suggestive SNPs associated with multiparous NBA. The SNP (rs81447100) within this region was confirmed to be significantly (P<0.05) associated with litter size in Erhualian (n=313), Sutai (n=173) and Yorkshire (n=488) populations. Retinol binding protein 2 and retinol binding protein 1 functionally related to the development of uterus were located in a region of 2 Mb around rs81447100. Moreover, four genes related to embryo implantation and development were also detected around other significant SNPs. Taken together, our findings provide a potential marker (rs81447100) for the genetic improvement of litter size not only in Chinese Erhualian pigs but also in European commercial pig breeds like Yorkshire, and would facilitate the final identification of causative variant(s) underlying the effect of SSC13 QTL on litter size.
We report our investigations on the host galaxy properties of stellar binary black holes (SBBHs) by implementing simple recipes for SBBH formation and merger into cosmological galaxy formation model. If the time delay between SBBH formation and merger ranges from Gyr to the Hubble time, SBBH mergers at redshift z < 0.3 occur preferentially in big galaxies with stellar mass M* > 2 × 1010M⊙ and metallicities Z peaking around ~0.6Z⊙. However, the host galaxy stellar mass distribution of heavy SBBH mergers (with total black hole mass >50M⊙) is bimodal with one peak at ~109M⊙ and the other peak at ~2 × 1010M⊙. The contribution fraction from metal-poor host galaxies (Z < 0.2Z⊙) to heavy mergers is much larger than that to less heavy mergers. If SBBHs were formed in the early universe, their mergers detected at z < 0.3 occur preferentially in even more massive galaxies with M* > 3 × 1010M⊙ and in galaxies with metallicities mostly >0.2Z⊙ and peaking at Z ~ 0.6Z⊙.
Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other.
We studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes.
Using harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility.
Combining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.
Vortex-induced vibration (VIV) is an important physical phenomenon as one design a riser or a cylindrical structure in ocean. As the riser or the cylindrical structure is adjacent to a seabed, the boundary effect on VIV is not fully understood yet. The direct-forcing immersed boundary (DFIB) method is used to investigate a two-degree-of-freedom VIV of a flexible supported circular cylinder adjacent to a plane boundary in this study. Furthermore, the effect of the VIV of cylinder on skin friction of the plane boundary is investigated. The effects of varying reduced velocity and gap ratio on VIV are discussed. Only a single vortex street is found when the cylinder is close to plane boundary. Hydrodynamic coefficients of the freely vibrating cylinder are analyzed in time and spectral domains. Furthermore, nearly round oval-shaped motion is observed as the so-called lock-in phenomenon occurs. The skin friction of the plane boundary is predicted by the DFIB model. Results show that the vibrating cylinder in the boundary layer flow can reduce the friction effectively. This proposed DFIB model can be useful for the investigation of VIV of the structures under the plane boundary effect even for a small gap between the cylinder and the boundary.