We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, a single candidate event ...is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP-nucleon cross section of 1.4×10^{-44} (1.0×10^{-44}) cm^{2} at 46 GeV/c^{2}. These results set the strongest limits for WIMP-germanium-nucleus interactions for masses >12 GeV/c^{2}.
BACKGROUND: Laparoscopic bipolar coagulation of uterine vessels (LBCUV) has been employed for women with symptomatic uterine myomas, but its effect on subsequent pregnancy has not been characterized. ...METHODS: Four‐hundred and twenty‐three women entered the study between March 1999 and December 2001. Of these, 142 women (33.6%) were under the age of 40 years at the time of LBCUV, 36 of whom (36/142, 25.3%) were sexually active without contraception. In a prospective study of 142 patients (<40 years old) undergoing LBCUV for symptomatic myomas, 15 women became pregnant (17 total pregnancies) and were evaluated by physical and ultrasound examinations. RESULTS: The volume of the dominant myoma was 117.4 ± 118.4 and 36.8 ± 56.8 cm3 before and after LBCUV respectively. Volume of the dominant myoma after pregnancy was 46.2 ± 76.7 cm3 (mean ± SD). There was a significant difference in myoma volume before and after LBCUV (P = 0.002), but no significant difference in myoma volume when comparing post‐partum size with post‐LBCUV size (P = 0.269). Pregnancy outcomes included seven miscarriages in the first trimester and one premature rupture of membrane (PPROM). Although the other pregnancies were regarded as uncomplicated, only two women were delivered of normal neonates as the other seven pregnancies were terminated secondary to patient request. CONCLUSIONS: The pregnancy and term pregnancy rates in sexually active women without contraception were 41.6% (15/36) and 5.6% (2/36) respectively. Because a relatively high rate (7/17, 41.2%) of early miscarriages was observed, we recommend that this procedure be employed only for women who do not desire additional children.
For high-risk neuroblastoma, planning target volume coverage is often compromised to respect adjacent kidney tolerance. This trial investigated whether intensity-modulated arc radiotherapy techniques ...(IMAT) could facilitate dose escalation better than conventional techniques.
Children with high-risk abdominal neuroblastoma referred for radiotherapy to the primary tumour site and involved regional lymph nodes were randomised to receive either standard dose (21 Gy in 14 fractions) or escalated dose (36 Gy in 24 fractions) radiotherapy. Dual planning with both a conventional anterior-posterior parallel opposed pair radiotherapy technique and an IMAT technique was performed. The quality of target volume and organ-at-risk delineation, and dosimetric plans, were externally reviewed. Dosimetric parameters were used to judge the superior technique for treatment. This feasibility trial was not powered to detect improvement in outcome with dose escalation.
Between 2017 and 2020, 50 patients were randomised and dual-planned. The IMAT technique was judged more favourable in 48 patients. In all patients randomised to receive 36 Gy, IMAT would have permitted delivery of the full dose (median D50% 36.0 Gy, inter-quartile range 36.0–36.1 Gy) to the target volume, whereas dose compromise would have been required with conventional planning (median D50% 35.6 Gy, inter-quartile range 28.7–35.9 Gy).
IMAT facilitates safe dose escalation to 36 Gy in patients receiving radiotherapy for neuroblastoma. The value of dose escalation is now being evaluated in a current prospective phase III randomised trial.
•The standard tumour bed radiotherapy dose used for neuroblastoma is 21 Gy.•The optimal dose is uncertain, and a higher dose may lead to better local control.•Organ-at-risk tolerance may limit the desired dose to the target volume.•Intensity-modulated arc therapy facilitates better delivery of higher doses.
During embryo implantation in species with hemochorial placentation, such as the mouse and human, trophoblast cells of the
attached blastocyst penetrate the luminal epithelium of the endometrium ...before invasion into the endometrial stroma. Signs
of apoptosis were demonstrated in luminal endometrial epithelial cells (EEC) adjacent to the trophoblast cells; however, the
signaling mechanisms leading to apoptosis in EEC remain unclear. Because mitogen-activated protein kinases (MAPK) were shown
to mediate apoptosis in several model systems and found to be activated in the uterus during decidualization, the possible
involvement of MAPK during trophoblast-EEC interactions was studied. By coculturing BeWo human trophoblast spheroids with
RL95-2 human EEC monolayers to mimic the blastocyst-endometrial interaction, we found that most spheroids rapidly attached
to EEC monolayers and then progressively expanded, with marked dislodgment of EEC adjacent to the spreading trophoblast cells.
Immunoblotting analysis showed that both p38 MAPK and extracellular signal-regulated kinase (ERK) were activated in EEC after
coculture. However, only SB203580 (a p38 MAPK inhibitor), but not PD98059 (an ERK inhibitor), inhibited trophoblast outgrowth
on EEC monolayers through the suppression of p38 MAPK activation in EEC. Furthermore, trophoblast expansion caused prominent
EEC apoptosis at the spheroid-EEC interface, as detected by annexin V labeling and valyl-alanyl-aspartyl-O-methyl-fluoromethylketone
(which binds activated caspases) staining, and SB203580 significantly decreased the percentage of apoptotic cells. Our results,
based on a model of human trophoblast-EEC interactions, establish that trophoblast cells cause activation of p38 MAPK in EEC
and, consequently, induce apoptosis and displacement of EEC, a process that may facilitate implantation.
The aim of this study is to understand the current status of bone mineral density (BMD) among Taiwanese women and to determine the relationship between bone mass, weight, height and body mass index ...(BMI), and the proportion of osteoporosis sufferers, based on World Health Organization standards, in each age group. A total of 4689 women underwent lumbar vertebrae (L2-L4) BMD measurements, and 3529 women underwent femoral neck bone mineral density measurements. BMD was measured using dual-energy X-ray absorptiometry. Standards were based on the BMD of the 20- to 40-year-old age group, as were relationships between height, weight, BMI, and BMD. Pearson correlation revealed a positive relationship between body weight, BMI, and BMD in the femoral neck; other correlations were insignificant. The defined BMD value for a diagnosis of osteoporosis was 0.827 g/cm(2) for lumbar vertebrae and 0.605 g/cm(2) for the femoral neck. The proportion of osteoporosis calculated for each age group in the lumbar vertebrae group was: 40-49 years old, 8.25%; 50-59 years old, 8.62%; 60-69 years old, 14.14%; 70-79 years old, 14.25%; >80 years old, 16.07%. For the femoral neck group, the values were: 40-49 years old, 5.24%; 50-59 years old, 5.28%; 60-69 years old, 11.17%; 70-79 years old, 17.30%; >80 years old, 24%. The total proportion of osteoporosis in the lumbar vertebrae was 10.08%, and in the femoral neck, 7.45%. The BMD of Taiwanese women shows a positive relationship to body weight and BMI in the femoral neck group but not in the lumbar vertebrae group. The proportion of osteoporosis by age group in this cohort was lower than that among Western women.
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood ...pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
This letter reports a new method using boron plasma doping and nanosecond laser annealing for further improvement of contact engineering. Up to 8% device performance improvement is demonstrated by ...using this technique in a conventional FinFET architecture. The key value of this letter relies on the plasma doping of fin vertical sidewalls and the super-activation of dopants, without any volume consumption between the epitaxial source and the drain. Furthermore, the TCAD simulation result points out that combining this method with the wrap-around contact structure can double the boost of transistor performance. We believe that this will bring us a new milestone in ultra-low contact resistance.
The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) ...assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN).
Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon’s two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME).
Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME.
Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.
•The combination of Isa + Atezo was well tolerated, showing a manageable safety profile.•Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment.•Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME.•CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.
To understand reasons for cytomegalovirus (CMV) recurrence, a cohort of 350 CMV-seropositive pregnant women attending obstetric clinics in Taiwan was examined for cervical or urinary CMV shedding. ...Urine specimens were collected from 350 women and cervical secretion specimens were collected from 220 women. We measured the association of various factors with CMV recurrence, which was defined as viral shedding identified by the presence of a CMV-specific gene sequence amplified by the polymerase chain reaction in seropositive individuals. CMV recurrence status was independently associated with a sexual activity composite variable, which was defined by three sexual activity indicators: age at first sexual intercourse, total years of sexual experience, and average frequency of sexual intercourse prior to pregnancy. Pregnant women with a history of genital tract infection were more likely than women without such history to experience cervical CMV recurrence. Similarly, pregnant women with previous urinary tract infections were more likely to experience urinary CMV recurrence. The findings indicate that multiple exposure to CMV by sexual activity prior to pregnancy is an important determinant of CMV recurrence during pregnancy.
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