OncoSNIPE® Study Protocol, a study of molecular profiles associated with development of resistance in solid cancer patients.

BACKGROUND: Nowadays, evaluation of the efficacy and the duration of treatment, in context of monitoring patients with solid tumors, is based on the RECIST methodology. With these criteria, resistance and/or insensitivity are defined as tumor non-response which does not allow a good understanding of the diversity of the underlying mechanisms. The main objective of the OncoSNIPE® collaborative clinical research program is to identify early and late markers of resistance to treatment. METHODS: Multicentric, interventional study with the primary objective to identify early and / or late markers of resistance to treatment, in 600 adult patients with locally advanced or metastatic triple negative or Luminal B breast cancer, non-small-cell lung cancer or pancreatic ductal adenocarcinoma. Patients targeted in this study have all rapid progression of their pathology, making it possible to obtain models for evaluating markers of early and / or late responses over the 2-year period of follow-up, and thus provide the information necessary to understand resistance mechanisms. To explore the phenomena of resistance, during therapeutic response and / or progression of the pathology, we will use a multidisciplinary approach including high-throughput sequencing (Exome-seq and RNAseq), clinical data, medical images and immunological profile by ELISA. Patients will have long-term follow-up with different biological samples, at baseline (blood and biopsy) and at each tumoral evaluation or tumoral progression evaluated by medical imaging. Clinical data will be collected through a dedicated Case Report Form (CRF) and enriched by semantic extraction based on the French ConSoRe (Continuum Soins Recherche) initiative, a dedicated Semantic Clinical Data Warehouse (SCDW) to cancer. The study is sponsored by Oncodesign (Dijon, France) and is currently ongoing. DISCUSSION: The great diversity of intrinsic or acquired molecular mechanisms involved in resistance to treatment constitutes a real therapeutic issue. Improving understanding of mechanisms of resistance of cancer cells to anti-tumor treatments is therefore a major challenge. The OncoSNIPE cohort will lead to a better understanding of the mechanisms of resistance and will allow to explore new mechanisms of actions and to discover new therapeutic targets or strategies making it possible to circumvent the escape in different types of cancer. TRIAL REGISTRATION: Clinicaltrial.gov. Registered 16 September 2020, https://clinicaltrials.gov/ct2/show/NCT04548960?term=oncosnipe&draw=2&rank=1 and ANSM ID RCB 2017-A02018-45.

On the Frequency Carrier Offset and Symbol Timing Estimation for CCSDS 131.2-B-1 High Data-Rate Telemetry Receivers.

In recent years there have been significant developments in satellite transmitter technology to follow the rapid innovation of sensors on-board new satellites. The CCSDS 131.2-B-1 standard for telemetry downlink, released in 2012, is part of the next generation of standards that aims to support the increased data-rate caused by these improvements in resolution. As a result of its relative novelty, this standard currently lacks in-depth analysis by researchers, but it is also strongly supported by the European Space Agency (ESA) for future missions. For these reasons, it seems important to evaluate how major receiver sub-components, such as timing recovery and carrier frequency correction, can be designed and implemented in new receivers that support this standard. The timing error detectors (TED) and frequency error detectors (FED) were therefore studied on the specific peculiarities of CCSDS 131.2-B-1 in its usual environment of Low Earth Orbit (LEO). Estimators have been evaluated highlighting performances, trade-offs and peculiarities of each one with respect to corresponding architectural choices. Finally, a receiver architecture derived from the paper considerations is proposed in the aim of supporting very different mission scenarios. Specifically, the realized architecture employs a parallel feedforward estimator for the timing recovery section and a novel multi-algorithm feedback frequency correction loop to efficiently cover both low symbol rates (5 Mbaud) and high data-rates (up to 500 Mbaud). This solution represents a good trade-off to support these scenarios in a very compact footprint by pushing the clock frequency to the FPGA limit. The FPGA resources occupation on a Zynq Ultrascale+ RFSoC XCZU28DR FPGA is 5202 LUT, 4851 FF, 5 BRAM, and 21 DSP for the timing recovery part, while the frequency recovery section occupies 1723 LUT, 1511 FF, 2.5 BRAM and 32 DSP.

'I wanted to talk about it, but I couldn't', an H70 focus group study about experiencing depression in early late life.

BACKGROUND: Knowledge about experiences of depression among younger-old adults from the general population is limited. The aim was to explore experiences of depression in early late life. METHODS: Sixteen participants in the population-based Gothenburg H70 Birth Cohort Studies (12 women and 4 men) who had reported a history of depression between ages 60-70 took part in focus group discussions (n = 4). Data were analyzed using focus group methodology. RESULTS: The analysis resulted in the overall theme 'I wanted to talk about it, but I couldn't'. The participants expressed unmet needs of communication about depression with family, friends, and healthcare staff. Participants wanted to know more about the causes and effects of depression, available treatment options and how to avoid recurrence. Lack of knowledge was a source of frustration; trust in health care providers was diminished. Being retired meant that opportunities for communication with co-workers were no longer available, and this made it harder to break negative thought and behavioral patterns. Being depressed meant losing one's normal self, and participants were grieving this. Thoughts of death and suicide were experienced in solitude; knowing that there was an escape could generate a feeling of comfort and control. CONCLUSIONS: Younger-old adults have expressed a need to talk about their experiences of depression. They would like to know more about available treatments, potential side effects, and how to avoid recurrence. Care providers also need to be aware there is a need for an existential dialogue about death.

What are Probable Olfactory Markers of Alcohol Dependence?

As the olfactory system is closely connected with the brain areas responsible for the most crucial alterations in psychiatric populations, especially cognitive and emotional impairments, the study of olfactory processing may be a relevant approach to identify specific markers of alcohol dependence. The aim of this study was to propose the probable olfactory markers for alcohol dependence through a study of the olfactory parameters that involve the central olfactory pathway. We recruited the same 41 alcohol-dependent patients in an early (day 8) and late (day 67) stage of abstinence and 41 controls matched for gender, age, and smoking status. The participants underwent clinical assessments and several olfactory evaluations. The results revealed on one hand, the persistence of decreased intensity of positive emotion (happy), increased intensity of negative emotion (sad), and increased citation of surprise in patients, suggesting the presence of probable trait markers of alcohol dependence. On the other hand, we found decreased hedonic score for pleasant and neutral odorants, and decreased odor familiarity judgment only in the early stage of evaluation as probable state markers for alcohol dependence. These results may be underpinned by several neuropsychological alterations specific to this disease and their evolution after weaning. Further studies are needed to replicate these findings and to confirm the specificity and sensitivity of the olfactory tests in a larger sample of patients. The olfactory perception of all controls must be also retested in order to determine the specific state and/or trait markers of alcohol dependence.

Early-Late Heterometallic Complexes of Gold and Zirconium: Photoluminescence and Reactivity.

OH functionalized triarylphosphines were used to assemble zirconocene-based metalloligands with phosphine donor sites in varying positions. These complexes were subsequently treated with different gold precursors to obtain early-late heterometallic compounds in which the metal atoms exhibit different intermetallic distances. All compounds were fully investigated by spectroscopic techniques, photoluminescence measurements and single crystal X-ray diffraction. Quantum chemical calculations were also performed. Some compounds show bright emission even at room temperature with quantum yields of up to 19 % (excitation at 350 nm). Furthermore, the reactivity of dimethyl zirconocene derivatives towards gold complexes was investigated, revealing simultaneous ligand exchange and transmetallation reactions.

Late Stone Age human remains from Ishango (Democratic Republic of Congo): New insights on Late Pleistocene modern human diversity in Africa.

Although questions of modern human origins and dispersal are subject to intense research within and outside Africa, the processes of modern human diversification during the Late Pleistocene are most often discussed within the context of recent human genetic data. This situation is due largely to the dearth of human fossil remains dating to the final Pleistocene in Africa and their almost total absence from West and Central Africa, thus limiting our perception of modern human diversification within Africa before the Holocene. Here, we present a morphometric comparative analysis of the earliest Late Pleistocene modern human remains from the Central African site of Ishango in the Democratic Republic of Congo. The early Late Stone Age layer (eLSA) of this site, dated to the Last Glacial Maximum (25-20 Ky), contains more than one hundred fragmentary human remains. The exceptional associated archaeological context suggests these remains derived from a community of hunter-fisher-gatherers exhibiting complex social and cognitive behaviors including substantial reliance on aquatic resources, development of fishing technology, possible mathematical notations and repetitive use of space, likely on a seasonal basis. Comparisons with large samples of Late Pleistocene and early Holocene modern human fossils from Africa and Eurasia show that the Ishango human remains exhibit distinctive characteristics and a higher phenotypic diversity in contrast to recent African populations. In many aspects, as is true for the inner ear conformation, these eLSA human remains have more affinities with Middle to early Late Pleistocene fossils worldwide than with extant local African populations. In addition, cross-sectional geometric properties of the long bones are consistent with archaeological evidence suggesting reduced terrestrial mobility resulting from greater investment in and use of aquatic resources. Our results on the Ishango human remains provide insights into past African modern human diversity and adaptation that are consistent with genetic theories about the deep sub-structure of Late Pleistocene African populations and their complex evolutionary history of isolation and diversification.

Polymorphisms in endothelial nitric oxide synthase gene in early and late severe preeclampsia.

Preeclampsia (PE) is characterized by hypertension and proteinuria, occurring after the 20th week of pregnancy in women who have had no previous symptoms. The disease progresses with generalized vasoconstriction and endothelial dysfunction. Clinically, it is important to diagnose the severe form of the disease (sPE), in which blood pressure and proteinuria are much higher. Recently, the gestational age (GA) of the onset of PE has led to the classification of this disease as early (GA <34 weeks) and late (GA ≥34 weeks). Several genetic polymorphisms affecting endothelial nitric oxide synthase (eNOS) levels or function were described, including G894T (Glu298Asp), VNTR b/a (variable-number 27-bp tandem repeat) and T-786C (promoter) polymorphisms. Thus, the aim of this study was to compare the distribution of G894T, VNTR b/a and T-786C polymorphisms and their haplotypes in Brazilian early and late sPE, as well as in normotensive pregnant. A total of 201 women were evaluated, 53 with early sPE, 45 with late sPE and 103 as normotensive pregnant women. The frequency of 894T allele was higher in late sPE vs normotensive pregnant, and 894TT genotype was higher in late sPE vs early sPE and normotensive pregnant. For VNTR b/a polymorphism, higher frequencies of aa genotype and a allele were observed in early sPE vs late sPE and normotensive pregnant. Besides, the frequency of haplotype T-b-C was higher in late sPE vs early sPE and normotensive pregnant. Considering the results found for eNOS polymorphisms, it is possible to suggest that the functional alterations induced by these two polymorphisms may influence the time of severe PE onset, although both alterations are putatively associated with low NO bioavailability. However, other studies are necessary to validate these findings and clarify this issue.

Evaluating sleep-stage classification: how age and early-late sleep affects classification performance.

Sleep stage classification is a common method used by experts to monitor the quantity and quality of sleep in humans, but it is a time-consuming and labour-intensive task with high inter- and intra-observer variability. Using wavelets for feature extraction and random forest for classification, an automatic sleep-stage classification method was sought and assessed. The age of the subjects, as well as the moment of sleep (early-night and late-night), were confronted to the performance of the classifier. From this study, we observed that these variables do affect the automatic model performance, improving the classification of some sleep stages and worsening others.

New Spinicaudatan Species of Late Jurassic Linglongta Phase of Yanliao Biota from Western Liaoning, China.

Abundant and diverse spinicaudatans are important components of the well-known Linglongta phase of the Yanliao Biota from the lower Upper Jurassic Tiaojishan Formation at the village Daxishan of Linglongta, Jianchang County, western Liaoning, north-eastern China. Herein a new spinicaudatan species Linglongtaestheria daxishanensis gen. and sp. nov. is described. It shows distinct carapace ornamentation patterns: (1) growth bands near the umbo ornamented with polygonal small-diameter reticulation; (2) growth bands in the middle part of the carapace ornamented with evenly distributed puncta; (3) growth bands in the ventral part of the carapace ornamented with punctate reticulation and radial lirae.

Low educational attainment is still associated with late melanoma diagnosis: A cross-sectional study from a European setting with universal healthcare.

BACKGROUND: An early diagnosis of cutaneous melanoma remains determinant for improved survival. Low educational attainment has been associated with a late-stage diagnosis in settings where access to healthcare is restricted. Little evidence is available from regions with universal healthcare. We aimed at analysing whether educational attainment was associated with Breslow thickness at diagnosis in a peripheral European region with universal healthcare (in the Canary Islands, Spain). METHODS: We conducted a cross-sectional study with prospectively collected data (2010-2017). Patients were recruited at diagnosis, and information about Breslow thickness, age at diagnosis, gender, highest educational attainment and site of melanoma were registered. Univariate and multivariate linear regression analyses were performed. RESULTS: Low educational attainment was associated with thicker tumours at diagnosis. The association remained true after adjustment for age, gender and site of melanoma. In the multivariate analysis, tumours diagnosed in patients with low educational attainment were on average 1.08 mm thicker (95% confidence interval: 0.36-1.81; p = 0.003) than those diagnosed in patients with high educational attainment. CONCLUSION: Public health strategies targeting this vulnerable group are currently needed in the Canary Islands (Spain).

Description of Neoxantholinus koghianus sp. n. and its larva from New Caledonia (Coleoptera, Staphylinidae, Xantholinini).

Neoxantholinus koghianus sp. n. (Coleoptera, Staphylinidae, Xantholinini) and the detailed external structure of its late (L2-3) and early (L1) larval instars from New Caledonia are described and illustrated. The morphological differences between L1 and L2-3 of N. koghianus sp. n. involve four characters. Diagnostic larval characters for the genus Neoxantholinus are given for the first time.

Timing of thoracic radiotherapy in the treatment of extensive-stage small-cell lung cancer: important or not?

BACKGROUND: This study evaluated the prognosis of patients with extensive-stage small-cell lung cancer (ES-SCLC) that may be associated with timing of thoracic radiotherapy (TRT). METHODS: ES-SCLC patients (n = 232) without progression were retrospectively analyzed after first-line induction chemotherapy. Patients in the TRT group were stratified as early-TRT (ERT; ≤3 cycles of induction chemotherapy received prior to TRT, n = 65) or late-TRT (LRT; >3 cycles, n = 122). To avoid selection bias, we conducted Propensity Score Matching (PSM) for patients. Overall survival (OS), progression-free survival (PFS), and locoregional recurrence-free survival (LRRFS) were assessed and compared. RESULTS: Overall, the median survival time, PFS, and LRRFS were 13.2, 8.7, and 14.6 months, respectively. After matching by PSM, there were 45 patients total in the TRT/non-TRT groups, and 56 patients total in the ERT/LRT groups. OS, PFS, and LRRFS were significantly longer in the TRT group than the non-TRT group (P < 0.001, all). However, between the ERT and LRT groups these survival parameters were similar (P > 0.05, all). CONCLUSION: For ES-SCLC patients without progression, the addition of TRT after first-line chemotherapy benefited survival greatly. Early TRT showed no significant benefit over late TRT.

Effect of late HIV diagnosis on HIV-related mortality among adults in general hospitals of Central Zone Tigray, northern Ethiopia: a retrospective cohort study.

BACKGROUND: The global incidence of HIV infection is not significantly decreasing, especially in sub-Saharan African countries, including Ethiopia. Though there is availability and accessibility of free HIV services, people are not being diagnosed early for HIV, and hence patients are still dying of HIV-related causes. This research is aimed at verifying the effect of late diagnosis of HIV on HIV-related mortality in Central Zone Tigray, Ethiopia. METHODS: A retrospective cohort study among adult (≥15 years old) HIV patients in three general hospitals of Tigray was conducted. Record reviews were carried out retrospectively from 2010 to 2015. Sample size was determined using stpower Cox in Stata software. Data were entered into EpiData version 3.1 software and transferred to Stata version 12 for analysis. Both bivariable and multivariable analyses were performed using Cox regression model to compare the HIV-related mortality of exposed (cluster of differentiation 4 cells count <350 cells/mm3) and nonexposed (≥350 cells/mm3) patients using adjusted hazard ratio (AHR) at 95% confidence interval (CI). RESULT: In all, 638 HIV patients were analyzed, contributing 2,105.6 person-years. Forty-eight (7.5%) patients died of HIV-related causes with a mortality rate of 2.28 per 100 person-years. In the multivariable Cox regression model, patients with late diagnosis of HIV had a higher risk of mortality (AHR =3.22, 95% CI: 1.17-8.82) than patients with early diagnosis of HIV. Rural residence (AHR =1.96, 95% CI: 1.05-3.68), unemployment (AHR =2.70, 95% CI: 1.03-7.08), bedridden patients (AHR =2.98, 95% CI: 1.45-6.13), ambulatory patients (AHR =2.54, 95% CI: 1.05-6.15), and baseline hemoglobin level of <11 mg/dL (AHR =3.06, 95% CI: 1.51-6.23) were other independent predictors of mortality. CONCLUSION AND RECOMMENDATIONS: Late diagnosis of HIV increased HIV-related mortality. Rural residence, unemployment, bedridden and ambulatory patients, and baseline hemoglobin level <11 mg/dL were also independent predictors of HIV-related mortality.

Early-late genes of the ecdysone cascade as models for transcriptional studies.

The DHR3 and Hr4 early-late genes of the ecdysone cascade are described as models for transcriptional studies in Drosophila cells. In a set of experiments, it became clear that these genes are a convenient and versatile system for research into the physiological conditions upon 20-hydroxyecdysone induction. DHR3 and Hr4 gene transcription is characterized by fast activation kinetics, which enables transcriptional studies without the influence of indirect effects. A limited number of activated genes (only 73 genes are induced one hour after treatment) promote the selectivity of transcriptional studies via 20-hydroxyecdysone induction. DHR3 and Hr4 gene expression is dose dependent, is completely controlled by the hormone titer and decreases within hours of 20-hydroxyecdysone withdrawal. The DHR3 and Hr4 gene promoters become functional within 20 minutes after induction, which makes them useful tools for investigation if the early activation process. Their transcription is controlled by the RNA polymerase II pausing mechanism, which is widespread in the genome of Drosophila melanogaster but is still underinvestigated. Uniform expression activation of the DHR3 and Hr4 genes in a cell population was confirmed at both the RNA and protein levels. Homogeneity of the transcription response makes DHR3/Hr4 system valuable for investigation of the protein dynamics during transcription induction.

The relationship between the stable carbon isotope composition of needle bulk material, starch, and tree rings in Picea abies.

We investigated the relationship between the δ13C signal in current-year and 1-year-old needle bulk material, starch extracts, and early- or late-wood in mature spruce trees (Picea abies) to identify the modifying influence of climatic conditions on the different δ13C signals. Seasonal patterns of δ13C were determined in total bulk needle material from 1998 to 2000, and in acid soluble starch extracts in 1999 and 2000, and δ13C values of early- and late-wood were measured for the years 1991-2000. δ13C of bulk needle material was most enriched in spring with a trend towards depletion in the course of the season. Current-year needles showed a more distinct seasonal pattern in δ13C compared to 1-year-old needles. Seasonal trends in bulk material and starch were similar, but the highly enriched signal in spring could not be fully explained by the influence of the δ13C values of starch (weighted with the corresponding starch amounts). δ13C of starch in 1-year-old needles, and to a lesser extent of current-year needles, correlated with δ13C of early-wood, indicating a transfer of the isotopic signal. In addition, early-wood δ13C corresponded weakly to winter precipitation. In the summer, δ13C of total bulk needle material and starch showed no relation to the late-wood δ13C signature. Late-wood δ13C, however, related to global radiation, relative humidity and temperature, with more enriched values corresponding to warmer and drier conditions. We conclude that the signature of early-wood is determined more by biochemical fractionation, e.g. during starch formation, than by climatic conditions, which exert only a minor influence and are reflected in the isotopic signal of late-wood.

Rasnitsynala sigambrorum gen. et sp. n., a small odonatopterid ("Eomeganisoptera", "Erasipteridae") from the early Late Carboniferous of Hagen-Vorhalle (Germany).

Besides Erasipteroides valentini (Brauckmann in Brauckmann, Koch & Kemper, 1985), Zessinella siope Brauckmann, 1988, and Namurotypus sippeli Brauckmann & Zessin, 1989, Rasnitsynala sigambrorumgen. et sp. n. is the fourth species of the Odonatoptera from the early Late Carboniferous (Early Pennsylvanian: Namurian B, Marsdenian) deposits of the important Hagen-Vorhalle Konservat-Lagerstätte in Germany. With its wing-span of about 55 mm it is unusually small even for the "Eomeganisoptera". Its venation resembles other small "Eomeganisoptera", in particular Zessinella siope. This is why it is here assigned to the probably paraphyletic "Erasipteridae" Carpenter, 1939.