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Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Inefficiencies in the national clinical research infrastructure have been apparent for decades. The National Center for Advancing Translational Science—sponsored Clinical and Translational Science Award (CTSA) program is able to address such inefficiencies. The Trial Innovation Network (TIN) is a collaborative initiative with the CTSA program and other National Institutes of Health (NIH) Institutes and Centers that addresses critical roadblocks to accelerate the translation of novel interventions to clinical practice. The TIN’s mission is to execute high-quality trials in a quick, cost-efficient manner. The TIN awardees are composed of 3 Trial Innovation Centers, the Recruitment Innovation Center, and the individual CTSA institutions that have identified TIN Liaison units. The TIN has launched a national scale single (central) Institutional Review Board system, master contracting agreements, quality-by-design approaches, novel recruitment support methods, and applies evidence-based strategies to recruitment and patient engagement. The TIN has received 113 submissions from 39 different CTSA institutions and 8 non-CTSA Institutions, with projects associated with 12 different NIH Institutes and Centers across a wide range of clinical/disease areas. Already more than 150 unique health systems/organizations are involved as sites in TIN-related multisite studies. The TIN will begin to capture data and metrics that quantify increased efficiency and quality improvement during operations.
Anxiety is debilitating and associated with numerous mental and physical comorbidities. There is a need to identify and investigate low-risk prevention and treatment strategies. Therefore, the purpose of this study was to investigate cross-sectional and longitudinal associations between different volumes of moderate-to-vigorous physical activity (PA) and anxiety symptoms and status among older adults in Ireland.
Participants (n = 4175; 56.8% female) aged ⩾50 years completed the International PA Questionnaire (IPAQ) at baseline, and the anxiety subscale of the Hospital Anxiety and Depression Scale at baseline and follow-up (2009–2013). Participants were classified according to meeting World Health Organisation PA guidelines, and divided into IPAQ categories. Respondents without anxiety at baseline (n = 3165) were included in prospective analyses. Data were analysed in 2017.
Anxiety symptoms were significantly higher among females than males (p < 0.001). Models were adjusted for age, sex, waist circumference, social class, smoking status and pain. In cross-sectional analyses, meeting PA guidelines was associated with 9.3% (OR = 0.91, 95% confidence interval 0.78–1.06) lower odds of anxiety. Compared with the inactive group, the minimally- and very-active groups were associated with 8.4% (OR = 0.92, 0.76–1.10) and 18.8% (OR = 0.81, 0.67–0.98) lower odds of anxiety, respectively. In prospective analyses, meeting guidelines was associated with 6.3% (OR = 0.94, 0.63–1.40) reduced odds of anxiety. Compared with the inactive group, the minimally and very-active groups were associated with 43.5% (OR = 1.44, 0.89–2.32) increased, and 4.3% (OR = 0.96, 0.56–1.63) reduced odds of anxiety. The presence of pain, included in models as a covariate, was associated with a 108.7% (OR = 2.09, 1.80–2.42) increase in odds of prevalent anxiety, and a 109.7% (OR = 2.10, 1.41–3.11) increase in odds of incident anxiety.
High volumes of PA are cross-sectionally associated with lower anxiety symptoms and status, with a potential dose–response apparent. However, significant associations were not observed in prospective analyses. The low absolute number of incident anxiety cases (n = 109) potentially influenced these findings. Further, as older adults may tend to experience and/or report more somatic anxiety symptoms, and the HADS focuses primarily on cognitive symptoms, it is plausible that the HADS was not an optimal measure of anxiety symptoms in the current population.
The relic “the sack of Saint Francesco” has for the first time been investigated by scientific means. The sack is kept at the Franciscan Friary of Folloni near Montella in southern Italy. According to legend, the sack appeared on the doorstep of the Friary in the winter of 1224 containing bread sent from St Francesco (St Francis of Assisi), who at that time was in France. The bread was allegedly brought to the friary by an angel. We analyzed samples of the sack to obtain a radiocarbon (14C) date and to search for any remaining traces of bread. The 14C date yielded a calibrated age range of AD 1220–1295 (2σ), which places the textile in the right timeframe according to the legend. Chemical analysis by gas-chromatography with mass spectrometric detection (GC-MS) revealed the presence of ergosterol (5, 7, 22-ergostatrien-3b-ol), a known biomarker of brewing, baking, or agriculture. In this paper we have further substantiated the validity of ergosterol as a biomarker for the past presence of bread. It appears that there is a fine correspondence between the Franciscan legend and the two most decisive scientific methods relevant for analyzing the sack. Although it is not proof, our analysis shows that the sack indeed could be authentic.
Individuals with chronic respiratory conditions may be at increased risk for pertussis. We conducted a retrospective administrative claims analysis to examine the incidence and economic burden of diagnosed pertussis among adolescents and adults in the USA with chronic obstructive pulmonary disease (COPD) or asthma. Patients aged ⩾11 years with diagnosed pertussis and pre-existing COPD (n = 343) or asthma (n = 1041) were matched 1:1 to patients with diagnosed pertussis but without COPD or asthma. Differences in all-cause costs (‘excess’ costs) during the 45-day and 3-month and 6-month periods before and after the pertussis index date were calculated; adjusted excess costs were estimated via multivariate regressions. The incidence of diagnosed pertussis was higher among patients with COPD or asthma than among matched patients. Compared with matched patients, patients with pertussis and pre-existing COPD or asthma accrued greater all-cause adjusted costs across study periods ($3694 and $1193 more, respectively, in the 45-day period; $4173 and $1301 more in the 3-month period; and $6154 and $1639 more in the 6-month period; all P < 0·0001). Patients with pre-existing COPD or asthma experience an increased economic burden after diagnosed pertussis and may especially benefit from targeted tetanus, diphtheria, and acellular pertussis vaccination strategies.
During the period from 1995 to 2011, radiocarbon measurements from the coast around Hartlepool in NE England have revealed anomalous enrichments in seawater, sediment, and marine biota. These cannot be explained on the basis of atomic weapons testing or authorized nuclear industry discharges, including those from the nearby advanced gas-cooled reactor. Enhanced 14C-specific activities have also been observed since 2005 in biota during routine monitoring at Hartlepool by the Food Standards Agency, but are reported as “likely” originating from a “nearby non-nuclear source.” Studies undertaken in Hartlepool and Teesmouth during 2005 and 2011 suggest that the 14C discharges are in the vicinity of Greatham Creek, with activity levels in biota analogous to those measured at Sellafield, which discharges TBq activities of 14C per annum. However, if the discharges are into Greatham Creek or even the River Tees, it is proposed that they would be much smaller than those at Sellafield and the high specific activities would be due to much smaller dilution factors. The discharge form of the 14C remains unclear. The activity patterns in biota are similar to those at Sellafield, suggesting that initial inputs are dissolved inorganic carbon (DI14C). However, the mussel/seaweed ratios are more akin to those found around Amersham International, Cardiff, which is known to discharge 14C in an organic form. 14C analysis of a sediment core from Seal Sands demonstrated excess 14C to the base of the core (43–44 cm). 210Pb dating of the core (0–32 cm) produced an accumulation rate of 0.7 g cm−2 yr−1, implying that 14C discharges have occurred from the 1960s until the present day.
From 1994 onwards, radiocarbon discharges from the Sellafield nuclear fuel reprocessing plant have been made largely to the northeast Irish Sea. They represent the largest contributor to UK and European populations of the collective dose commitment derived from the entire nuclear industry discharges. Consequently, it is important to understand the long-term fate of 14C in the marine environment. Research undertaken in 2000 suggested that the carbonate component of northeast Irish Sea sediments would increase in 14C activity as mollusk shells, which have become enriched in Sellafield-derived 14C, are broken down by physical processes including wave action and incorporated into intertidal and subtidal sediments. The current study, undertaken in 2011, tested this hypothesis. The results demonstrate significant increases in 14C enrichments found in whole mussel shells compared to those measured in 2000. Additionally, in 2000, there was an enrichment above ambient background within only the largest size fraction (>500 μm) of the intertidal inorganic sediment at Nethertown and Flimby (north of Sellafield). In comparison, the present study has demonstrated 14C enrichments above ambient background in most size fractions at sites up to 40 km north of Sellafield, confirming the hypothesis set out more than a decade ago.
The new 1 m f/4 fast-slew Zadko Telescope was installed in June 2008 about 70 km north of Perth, Western Australia. It is the only metre-class optical facility at this southern latitude between the east coast of Australia and South Africa, and can rapidly image optical transients at a longitude not monitored by other similar facilities. We report on first imaging tests of a pilot program of minor planet searches, and Target of Opportunity observations triggered by the Swift satellite. In 12 months, 6 gamma-ray burst afterglows were detected, with estimated magnitudes; two of them, GRB 090205 (z = 4.65) and GRB 090516 (z = 4.11), are among the most distant optical transients imaged by an Australian telescope. Many asteroids were observed in a systematic 3-month search. In September 2009, an automatic telescope control system was installed, which will be used to link the facility to a global robotic telescope network; future targets will include fast optical transients triggered by high-energy satellites, radio transient detections, and LIGO gravitational wave candidate events. We also outline the importance of the facility as a potential tool for education, training, and public outreach.
In the last decades many techniques have been proposed to manufacture thin (<50µm) silicon solar cells. The main issues in manufacturing thin solar cells are the unavailability of a reliable method to produce thin silicon foils with contained material losses (kerf-losses) and the difficulties in handling and processing such fragile foils. A way to solve both issues is to grow an epitaxial foil on top of a weak sintered porous silicon layer. The porous silicon layer is formed by electrochemical etching on a thick silicon substrate and then annealed to close the top surface. This surface is employed as seed layer for the epitaxial growth of a silicon layer which can be partially processed while attached on the substrate that provides mechanical support. Afterward, the foil can be bonded on glass, detached and further processed at module level. The efficiency of the final solar cell will depend on the quality of the epitaxial layer which, in turn, depends on the seed layer smoothness.
Several parameters can be adjusted to change the morphology and, hence, the properties of the porous layer, both in the porous silicon formation and the succeeding thermal treatment. This work focuses on the effect of the parameters that control the porous silicon formation on the structure of the porous silicon layer after annealing and, more specifically, on the roughness of the top surface. The reported analysis shows how the roughness of the seed layer can be reduced to improve the quality of the epitaxial growth.
The Spitzer Legacy Program “Surveying the Agents of Galaxy Evolution in the Tidally-Stripped, Low-Metallicity Small Magellanic Cloud” (SAGE-SMC; Gordon et al. 2011) allows a global study of star formation in the SMC at high enough resolution to resolve individual cores and protostars at a range of mid-IR wavelengths. Using the SAGE-SMC IRAC (3.6 - 8.0 μm) and MIPS (24 and 70 μm) catalogs and images combined with the near-IR and optical data, we identified a population of ∼1100 intermediate- to high-mass Young Stellar Objects (YSOs) in the SMC (3 × more than previously known). We investigate the properties of the YSOs and how they relate to the galaxy's structure and gas and dust distribution.