In the past decade, the field of cancer immunotherapy has been revolutionized by immune checkpoint blockade (ICB) technologies. Success across a broad spectrum of cancers has led to a paradigm shift ...in therapy for patients with advanced cancer. Early data are now accumulating in progressive thyroid cancers treated with single-agent ICB therapies and combination approaches that incorporate ICB technologies. This Review discusses our current knowledge of the immune response in thyroid cancers, the latest and ongoing immune-based approaches, and the future of immunotherapies in thyroid cancer. Physiologically relevant preclinical mouse models and human correlative research studies will inform development of the next stage of immune-based therapies for patients with advanced thyroid cancer.
Inequality between and within populations has origins in adverse early experiences. Developmental neuroscience shows how early biological and psychosocial experiences affect brain development. We ...previously identified inadequate cognitive stimulation, stunting, iodine deficiency, and iron-deficiency anaemia as key risks that prevent millions of young children from attaining their developmental potential. Recent research emphasises the importance of these risks, strengthens the evidence for other risk factors including intrauterine growth restriction, malaria, lead exposure, HIV infection, maternal depression, institutionalisation, and exposure to societal violence, and identifies protective factors such as breastfeeding and maternal education. Evidence on risks resulting from prenatal maternal nutrition, maternal stress, and families affected with HIV is emerging. Interventions are urgently needed to reduce children's risk exposure and to promote development in affected children. Our goal is to provide information to help the setting of priorities for early child development programmes and policies to benefit the world's poorest children and reduce persistent inequalities.
Mechanical metamaterials exhibit some superior mechanical properties such as ultrahigh strength-to-weight ratio, negative bulk-modulus, negative stiffness, negative mass-density, and negative ...Poisson's ratio. These advantages led to a variety of applications, especially in vibration isolation, by targeting and tuning for a specific frequency-range called stopband. The tuning ability is achieved from its array of unit-cells, which can be topologically optimized for the desired frequency range. This review discusses the development of mechanical metamaterials and focuses on its vibration control applications by using passive and active approaches for stopband enhancement and broadening the bandwidth at varying frequency-ranges.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This work designs and analyzes a metastructure-based vibration isolation model to improve small-scale equipment's isolation effectiveness under low-frequency excitations. The feature of the proposed ...model is the high static and low dynamic stiffness characteristics, also called quasi-zero-stiffness (QZS), possessed by the metastructure under vertical load. The metastructure consists of four parallelly arranged unit cells, and the QZS property is realized in each unit cell by the snap-through behavior of the cosine beam system and the bending-dominated behavior of semicircular arches. The static characteristics of the metastructure are studied analytically and numerically and validated with experimental results. Based on the static analysis results, the dynamic equation of the proposed metastructure is set up in the form of Duffing's equation. The harmonic balance method is used to calculate the frequency response and motion transmissibility of the metastructure at steady state for a harmonic load. The time and frequency responses under the sinusoidal base excitation are examined analytically and numerically, and their results are compared. The simulation results revealed that the proposed QZS metastructure obtains lower transmissibility and wider effective isolation range compared to the equivalent linear model. The parametric study shows that in the low-frequency excitation region, the motion transmissibility increases with decreasing damping ratio, whereas for the effective isolation range, the motion transmissibility increases with increasing damping ratio. Finally, stability analysis is performed to study the unstable region in the frequency response curve. The parametric study indicates that the unstable region reduces with the increase in damping ratio and remains unaffected with varying excitation amplitude.
To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance.
The ...genetic profiles of 583 advanced differentiated and 196 ATCs generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed.
ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared with other thyroid cancer types. DNA mismatch repair deficit and activity of APOBEC cytidine deaminases were identified as mechanisms associated with high mutational burden in a subset of differentiated thyroid cancers and ATCs. Copy number losses and mutations of
and
, amplification of
, amplification of receptor tyrosine kinase genes
, and
, amplification of immune evasion genes
, and
, and activating point mutations in small GTPase
were associated with ATC. An association of
, and
amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown
Three genetically distinct types of ATCs are proposed.
This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed.
.
Background: Cadmium (Cd) is an embryotoxic and teratogenic metal in a variety of animal species, but data from humans are limited. Objectives: The aim of the present study was to assess the effects ...of maternal Cd exposure in pregnancy on size at birth. Methods: This prospective cohort study was nested in a population-based nutritional supplementation trial in pregnancy conducted in rural Bangladesh. We selected women recruited from February 2002 through January 2003 who had a singleton birth with measurements of size at birth and had donated a urine sample in early pregnancy for Cd analyses (n = 1,616). Urinary Cd was measured with inductively coupled plasma mass spectrometry and adjusted for specific gravity. Results: Multiple linear regression analyses adjusted for sex and other potential confounders showed that maternal urinary Cd (median, 0.63 µg/L) was significantly negatively associated with birth weight unstandardized regression coefficient B = -31.0; 95% confidence interval (CI): -59, -2.8 and head circumference (B = -0.15; 95% CI: -0.27, -0.026). However, associations appeared to be limited to girls, with little evidence of effects in boys. A 1-µg/L increase in Cd in maternal urine was associated with a 0.26-cm (95% CI: -0.43, -0.088 cm) and 0.24-cm (95% CI: -0.44, -0.030 cm) decrease in girls' head and chest circumferences, respectively, and a 45-g (95% CI: -82.5, 7.3 g) decrease in birth weight. Quantile regression analyses indicated that associations with maternal Cd were similar for girls of smaller (25th percentile) and larger (50th and 75th percentiles) sizes at birth. Conclusion: We found evidence of a sex difference in the association between maternal Cd exposure and birth size, which was apparent only in girls. Results add support for the need to reduce Cd pollution to improve public health.
Ultrawide‐bandgap (UWBG) semiconductors, with bandgaps significantly wider than the 3.4 eV of GaN, represent an exciting and challenging new area of research in semiconductor materials, physics, ...devices, and applications. Because many figures‐of‐merit for device performance scale nonlinearly with bandgap, these semiconductors have long been known to have compelling potential advantages over their narrower‐bandgap cousins in high‐power and RF electronics, as well as in deep‐UV optoelectronics, quantum information, and extreme‐environment applications. Only recently, however, have the UWBG semiconductor materials, such as high Al‐content AlGaN, diamond and Ga2O3, advanced in maturity to the point where realizing some of their tantalizing advantages is a relatively near‐term possibility. In this article, the materials, physics, device and application research opportunities and challenges for advancing their state of the art are surveyed.
Ultrawide‐bandgap (UWBG) semiconductors, with bandgaps significantly wider than the 3.4 eV of GaN, represent an exciting and challenging new area of research in semiconductor materials, physics, devices and applications. This article surveys and presents an enumerated list of the materials, physics, device and associated application research opportunities and challenges important for advancing the state of their science and technology.
Previously, in 30 Bangladeshi villages, 2 groups of children with iron-deficiency anemia (IDA) and nonanemic (NA) iron sufficiency aged 6 to 24 months participated in 2 parallel cluster randomized ...controlled trials of the effect of psychosocial stimulation on neurodevelopment. The intervention was composed of weekly play sessions at home for 9 months. All children with anemia received iron treatment of 6 months. The intervention improved the mental development of NA but not IDA groups. Six years after end line when the children were aged 8 to 9 years, we aimed to determine if benefits were sustained in the NA group or late-onset benefits emerged in the IDA group.
We relocated 372 (90%) of the initial 412 children from all the clusters (villages), and assessed their IQ with the Wechsler Abbreviated Scale of Intelligence-II, motor development, and school achievement including math, spelling, and reading. Analyses were by intention-to-treat, adjusting for clustering.
There was a significant interaction between anemia groups (IDA/NA) and intervention on IQ. The intervention benefitted the NA group's Full-Scale IQ (effect size, 0.43 95% confidence interval, 0.08-0.79) and Perceptual Reasoning Index (effect size, 0.48 95% confidence interval, 0.08-0.89) but did not affect the IDA group's outcomes. No other outcomes were significant.
The benefits from early childhood psychosocial stimulation on the NA group's IQ, 6 years after intervention ended, adds to the limited evidence on the sustainability of benefits in low- and middle-income countries. Reasons for lack of effect in children with anemia are unknown.
We aimed to determine the timing and size of the cognitive deficit associated with poverty in the first 5 years of life and to examine the role of parental characteristics, pre- and postnatal growth, ...and stimulation in the home in Bangladeshi children. We hypothesized that the effect of poverty on cognition begins in infancy and is mainly mediated by these factors.
We enrolled 2853 singletons, a subsample from a pregnancy supplementation trial in a poor rural area. We assessed mental development at 7, 18, and 64 months; anthropometry at birth, 12, 24, and 64 months; home stimulation at 18 and 64 months; and family's socioeconomic background. In multiple regression analyses, we examined the effect of poverty at birth on IQ at 64 months and the extent that other factors mediated the effect.
A mean cognitive deficit of 0.2 (95% confidence interval -0.4 to -0.02) z scores between the first and fifth wealth quintiles was apparent at 7 months and increased to 1.2 (95% confidence interval -1.3 to -1.0) z scores of IQ by 64 months. Parental education, pre- and postnatal growth in length, and home stimulation mediated 86% of the effects of poverty on IQ and had independent effects. Growth in the first 2 years had larger effects than later growth. Home stimulation had effects throughout the period.
Effects of poverty on children's cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in the first 5 years.
PDF
