Lower Age Limit Research Articles

Respektuje český zákonodárce princip subsidiarity trestní represe?

In this article the author expresses the conviction that it is necessary to continue to uphold the principle of subsidiarity of penal repression (other terms used are “the subsidiarity role of criminal law”, “the limitation of criminal law” or “the ultima ratio principle”), no matter how ambiguous the hitherto development of the Czech Republic’s criminal policy may have been. To assess the level of country’s criminal law repressiveness, we especially need to look at the scope of criminalization, i.e. the range of anti- social conduct against which the state applies criminal sanctions. Further elements to be considered are the severity of penal sanctions, the minimum age for criminal liability, the scope of circumstances excluding the illegality of an act, the conditions under which criminal liability of a person expires, the conditions under which criminal penalties are enforced, the rigor of procedural laws and above all the standard of fundamental human rights guarantees applicable during criminal proceedings. In the author’s view, the tendency towards more repression has prevailed in the draft of the new Czech Penal Code and is manifested mainly through the criminalization of acts that have so far not been considered criminal offences or have only very recently been introduced by amendment to the Penal Code (esp. by increasing the number of the “prematurely completed” offences and the abstract generally- endangering offences). Further, the draft includes longer prison terms and would introduce a lower age limit for criminal liability and more severe sanctions for particularly dangerous recidivists. The authors expresses serious doubts about this trend and points out its possible negative effects. In the final part the author speaks out for upholding the long-term objective of any modem criminal policy, which is to reintegrate offenders back into society instead of ostracizing them. The means to achieve this objective is the inclusion of offenders into the process of criminal prosecution and sentencing.

Stratified Fertility: Age Norms, Ideals, Behaviors, and the Role of National Contexts

A growing body of research shows that demographic attitudes and behaviors across the life course are socially stratified. Building on this and focusing on the transition to parenthood, we hypothesize that (i) parental socioeconomic status is associated with multiple dimensions of the transition to parenthood, including fertility norms (perceived lower age limit at first birth), ideals (ideal age at first birth), and behaviors (age at first birth), and that (ii) this association varies across national contexts, as national contexts determine the opportunities and constraints that guide young adults’ life course attitudes and behaviors. Drawing on the European Social Survey 2006 and 2018 data, we analyze early fertility norms and ideals and later fertility behaviors of a pseudo-panel of individuals born between 1976 and 1988. We show that (i) parental socioeconomic status is positively associated with later fertility norms, later fertility ideals, and later childbearing, even when controlling for respondents’ own socioeconomic status, and that (ii) national contexts partially moderate these associations. We conclude by discussing implications for theories of fertility and highlighting avenues for future research.

Late Paleozoic to Mesozoic tectonic evolution of the Qinling Orogenic Belt: Structural and geochronological constraints from the Devonian Liuling Group, eastern Qinling area, China

The Late Paleozoic to Mesozoic tectonic evolution of the Qinling Orogenic Belt is not fully understood. To address this, structural analysis and rutile U-Pb dating were performed on the Middle–Late Devonian Liuling Group located along the northern margin of the South Qinling Belt (SQB). Detailed structural analysis reveals that the Liuling Group experienced four main deformation events (D1–D4). Initial D1 deformation is characterized by intrafolial folds (F1) and a regional penetrative foliation (S1). Subsequent D2 is marked by SW-vergent asymmetric, overturned folds and related crenulation lineation (L2). D3 and D4 are represented by, respectively, nearly E-W trending open folds and NNE-SSW trending centimeter-scale kink folds, both of which slightly modify D1 and D2 structures. Taking into account published chronological data, we propose that D1 and D2 occurred at 363–349 Ma and 332–318 Ma, respectively, and were associated with NE-SW oriented shortening during continental subduction of the SQB. Our new rutile U-Pb ages of 243–240 Ma provide a lower age limit for D3 deformation, which was related to N-S oriented shortening triggered by continental collision between the South China Block (SCB) and SQB along the Mianlue Suture Zone (MLSZ). Finally, D4 deformation was associated with the far-field effects of Late Jurassic subduction of the Paleo-Pacific Plate, which generated a WNW-ESE oriented shortening. Our findings suggest that continental subduction of the SQB continued until the earliest Late Carboniferous. Subsequently, the northern margin of the SQB experienced a Triassic metamorphic overprint triggered by collision between the SCB and SQB.

Identifying eligibility criteria that perpetuate race/ethnic disparities in acute myeloid leukemia (AML) clinical trial participation.

1589 Background: The extent to which eligibility criteria perpetuate race/ethnic disparities in adult AML clinical trial participation is unknown. Methods: This multicenter cohort study counterfactually assessed race/ethnic disparities in trial eligibility between Non-Hispanic Whites (NHW) and Minoritized Individuals (MI: Hispanic, Black, Asian, and/or Other) diagnosed with AML between 2010-2022 at six hospitals in Chicago, IL and one in Boston, MA. All newly diagnosed patients were catalogued; those with complete data were analyzed. Eligibility criteria were obtained from 190 front-line phase II/III therapeutic studies active during the same period (1). Common sets of criteria for intensive and non-intensive trials were generated based on prevalent criteria and medians of any associated limits (e.g., QTc ≤480 ms). Proportions of MI and NHW that would have been eligible based on these common criteria sets were assessed using X2 tests with odds ratios (OR). Mann-Whitney U tests assessed differences in the median number of trials for which each MI and NHW patient would have been eligible. Analyses with MI groups disaggregated were also performed. Results: There were 1283 patients (405 MI, 878 NHW) with a median age of 60 years (57 MI, 61 NHW; p<0.001); 44% were female. According to the common set of 23 intensive trial criteria that was generated, similar proportions of MI and NHW were eligible (24.7% and 24.5%, OR 1.01, 95% CI [0.77,1.33]). With the age limit criterion removed, fewer MI than NHW were eligible (42.7% and 36.0%, OR 0.76, 95% CI [0.59,0.96]). In this set of criteria, prior malignancy (excluding 22.5% and 17.5%, p=0.04), prolonged QTc (17.0% and 8.7%, p<0.001), and coronary artery disease (CAD; 8.6% and 4.1%, p=0.002) generated the largest disparity individually. According to the non-intensive set (14 criteria), fewer MI were eligible than NHW (42.2% and 54.4%, OR 0.61, 95% CI [0.48,0.78]); there was no age criterion in this set. Prior malignancy (22.5% and 17.5%, p=0.04), prolonged QTc (20.5% and 12.8%, p<0.001), and hepatitis B infection (4.0% and 1.0%, p=0.001) generated the largest disparities in this set. Overall, individuals were eligible for a mean of 51.6% of the 190 trials (median: 98 trials, IQR [59,115]). MI were eligible for 6.8% fewer trials than NHW (median difference: 13 trials [88 and 101], p<0.001). Asian, Black, and Other were eligible for 7.7%, 4.8%, and 16.9% less trials than NHW, respectively (all p<0.05). Criteria with the largest individual disparities in median eligibility were lower age limits, hepatitis B, and CAD (all p<0.01). Conclusions: Eligibility criteria disparately exclude minoritized individuals from AML clinical trial participation. Based on ASCO recommendations ( 2), several of the criteria driving disparate eligibility (hepatitis, prior malignancy) are modifiable or removable. 1. Hantel, Haematologica, 2023. 2. ASCO, Clin Cancer Res, 2021.

ИСТОЧНИКИ И ПАЛЕОГЕОДИНАМИЧЕСКАЯ ОБСТАНОВКА НАКОПЛЕНИЯ ТЕРРИГЕННЫХ ОТЛОЖЕНИЙ НИЖНЕКЕМБРИЙСКОЙ БЫСТРИНСКОЙ СВИТЫ АРГУНСКОГО МАССИВА

The article presents the results of mineralogical, geochemical, isotopic, and geochemical (Sm-Nd) studies on siltstones from the upper Bystraya subformation of the Argun continental massif, as well as U-Pb dating of detrital zircon grains from them. The main goal of the research was to identify the main sources of clastic material, reconstruct the paleogeodynamic environment of accumulation, and constrain the lower age limit for the formation of terrigenous rocks of the upper Bystraya subformation. The mineralogical composition of the studied rocks indicates their accumulation in an environment associated with subduction processes. The trace element composition of siltstones from the subformation suggests the presence of rocks of mixed composition in the source area in terms of their silica content. Based on Sm-Nd isotopic and geochemical data, it was established that the main sources of clastic material for siltstones of the stratigraphic unit were Paleoproterozoic rocks and (or) younger rocks whose formation is associated with the reworking of the Paleoproterozoic continental crust. Most of the zircons from the studied sample of siltstones of the upper Bystraya subformation are Neo- and Paleoproterozoic in age. Their sources are probably Neo- and Paleoproterozoic igneous rocks widespread within the Argun massif in China. The age of the youngest zircons (556 ± 9 and 566 ± 10 Ma) isolated from siltstones of the upper Bystraya subformation was used to constrain the lower limit of their accumulation in the middle of the Ediacaran.

The stratigraphy and formation of Middle Stone Age deposits in Cave 1B, Klasies River Main site, South Africa, with implications for the context, age, and cultural association of the KRM 41815/SAM-AP 6222 human mandible

Cave 1B, in the Klasies River Main site complex (KRM), is best known for the recovery of the KRM 41815/SAM-AP 6222 human mandible. After initial skepticism over the modernity of this specimen, it is accepted that the mix of archaic and modern traits it displays is characteristic of early Homo sapiens individuals. Different authors have associated this specimen with the Middle Stone Age (MSA) I and II/Mossel Bay cultural phases, but the published data do not allow an unambiguous attribution. KRM 41815's frequent use in studies of the evolution of the human mandible, and its well-developed chin, makes clarifying its age and context important objectives. The field and micromorphology observations presented here provide greater insight into the stratigraphy and formation of the sequence exposed in the PP38 excavation. There are three major divisions: the basal Light Brown Sand (LBS) Member (not excavated), the Rubble Sand (RS) Member (MSA I), and the Shell and Sand Dark Carbonized (SASDC) Submember (MSA II). Cultural stratigraphy based on lithic artifacts remains the only way to make secure (but broad) temporal correlations with the rest of the site complex. This investigation shows that a range of anthropogenic, geogenic, and biogenic processes contributed to the deposition and post-depositional alteration of the identified microfacies. Short depositional hiatuses are reasonably common, and a significant hiatus was identified between the RS and SASDC. The impact of post-depositional processes on the RS is significant, with anthropogenic deposits poorly preserved. In comparison, the SASDC is dominated by hearths contained within deposits rich in reworked anthropogenic materials known as carbonized partings. Small shell disposal features are also present. The distribution of these anthropogenic features suggests continuity in the management of space throughout the MSA II occupations, from before 110 ka. New stratigraphic correlations indicate that KRM 41815 is unambiguously associated with the MSA I. Therefore, it predates 110 ka, with a lower age limit potentially in Marine Isotope Stage 6.

The Nature of the Puchezh-Katunki Impact Structure (the Central Part of the East European Platform): Results of the U‒Th‒Pb Isotope System Study of Detrital Zircons from Explosive Breccias

The Puchezh-Katunki crater is located in the central part of the East European Platform in the area of the Gorky Reservoir, has a diameter of ~80 km and is morphologically expressed by the central uplift of the basement (Vorotilov knoll) and the ring depression surrounding it, on the periphery of which there is a ring terrace. The crater is filled with various coptogenic (explosive (?)) formations – breccias of various types, bodies of suvites and tagamites. The results of studying the U‒Th‒Pb isotopic system of detrital zircon grains from variegated explosive Puchezh breccias in the northwestern part of the ring terrace (three samples) are presented. The weighted average of the three youngest U‒Pb datings of detrital zircon from all studied samples is 258 ± 7 Ma, which corresponds to the Late Permian. We took this dating as the lower age limit of the Puchezh breccias. A comparison of the age sets of detrital zircon grains from the samples studied by us and from (i) crystalline rocks of the Vorotilov knoll and ring depression suvites and (ii) Upper Permian–Lower Triassic sandstones of the Zhukov ravine reference section (Moscow syneclise) was carried out. The absence among the detrital zircon from the Puchezh breccia grains, whose U‒Th‒Pb isotopic system is comparable with the parameters of zircon from the rocks of the Vorotilov knoll and suvites, indicates the local nature of the Puchezh-Katunki explosion, in which the impact-thermal impact did not affect the detrital zircons in rocks of the marginal part of the annular terrace of the crater. The high similarity of the sets of ages of detrital zircon grains from the lens of redeposited sandstones of the Puchezh breccias and Upper Permian rocks of the Zhukov ravine section indicates that the Puchezh breccias were formed mainly due to the recycling of the Upper Permian–Lower Triassic sequences underlying the explosive formations. We consider the Uralides paleoorogen as the main source for the deposits of the central regions of the East European Platform in the stratigraphic interval close to the Permian–Triassic boundary. The deposits were formed as a result of a high degree of mixing and averaging of clastic material of sedimentary flows containing the Uralian and Asha provenance signals.

Composition and Age of Sources of the Lower–Middle Cambrian (?) Terrigenous Rocks from The Ernichny Formation in the Argun Massif, Eastern Part of the Central Asian Fold Belt

The paper presents the results of the mineralogical and geochemical studies of sandstones and siltstones of the Ernichny formation of the Argun series in the Argun continental massif, and the results of U–Pb (LA‑ICP-MS) dating for the detrital zircons from these rocks. It is established that the youngest detrital zircons from sandstone of the Ernichny Formation have age of 549–570 Ma. A maximum on the relative probability curve of zircon age corresponds to 566 Ma. These data determine the lower age limit of their accumulation on the border of the Ediacaran and Paleozoic age. According to the results of U–Pb dating of detrital zircon, the majority of detrital zircons from sandstones of Ernichny Formation are characterized by Neo- and Paleoproterozoic ages. The sources of zircons were Neo- and Paleoproterozoic igneous and metamorphic rocks that were widely developed within the Argun continental massif. In turn, the geochemical features of the terrigenous rocks of the Ernichny Formation, together with the presence of the poorly sorted and rounded clastic material in the studied samples, as well as the presence of interlayers of gravelstones, enabled us to establish that they were formed in a subduction-related setting.

SP7.5 Should we analyse all cholecystectomy specimens? An analysis of the features of incidentally discovered gallbladder cancers

Abstract Aims Gallbladder cancer is the commonest form of malignancy of the biliary tract, but is rare in Western countries. A large proportion of cases are incidentally diagnosed at surgery or from the cholecystectomy specimen. The analysis of gallbladder specimens costs our health board around £42,000 per year. The aim was to identify any predictive factors in incidentally discovered gallbladder cancers. Methods All gallbladder specimen reports at our health board between May 2012 and September 2022 were analysed and filtered so incidental cancer cases could be analysed for any predictive features. Outcomes with only dysplasia were removed. Results 16,695 eligible reports were analysed of which 32 had malignant outcomes. The median age for malignancy was 71 vs 50 for benign. 30 were adenocarcinoma and 2 were adenosquamous carcinoma. 14 presented with cholecystitis, 9 with biliary colic, 6 with choledocholithiasis and 3 with gallstone pancreatitis. Intraoperatively, 7 had normal appearances, 20 were reported at being ‘thickened’, 2 ‘contracted’, 2 with empyema and 1 with a mucocoele. 6 patients had a subtotal cholecystectomy and in all cases this was due to intraoperative difficulty. Conclusions We could not identify any single feature that predicted or excluded the presence of cancer. Given that the lower age limit for malignancy was 51, a consideration could be made for not processing specimens from patients under the age of 45 as the likelihood of diagnosing incidental carcinoma is extremely unlikely and would reduce the yearly processing by 37% with a cost saving of £15,500 per year.

Myocardial contraction fraction: an underused imaging biomarker

Abstract Funding Acknowledgements Type of funding sources: None. Background The Myocardial contraction fraction (MCF% – stroke volume over myocardial volume) is an alternative/complementary measure of cardiac function to the ejection fraction (EF% – stroke volume over end diastolic volume), (1–2). It is dimensionless, does not need allometric scaling, is easy to compute and intuitive: the stroke volume produced per unit of myocardium, with some data for its utility in different forms of hypertrophy, (3–5). EF limitations (eg HFpEF) are well known. We explored the potential utility of MCF in a variety of cardiac diseases. Purpose To define reference ranges for MCF in normal and disease using a large dataset, exploring sex and age-related differences. To evaluate and compare the potential use of MCF as a prognostic biomarker compared to the more commonly used LVEF. Methods 3 cohorts were used: 1. Health: 3,541 subjects from UK biobank, supplemented by 72 local healthy volunteers (UKB lower age limit is 45) to define normality and age/sex differences. 2. Disease: n=380 with a range of diseases : 125 HCM, 157 Fabry disease (FD) and 26 Transthyretin (TTR) Amyloid. 3. Prognostic cohort: n=1500 patients from a single centre with outcomes (26% death or hospitalisation with heart failure over a median 5.5years follow-up) All CMR images were analysed using a clinically validated artificial intelligence (AI) algorithm for convenience of large-scale analysis (6) to determine MCF and LVEF. Results Health: There was no significant changes in MCF with age but there was a significant sex difference (male 0.94, range 0.68–1.2; female 1.10, range 0.82–1.37 p<0.05)—see figure 1. Disease: MCF values for each disease cohort is shown in figure 2, all with a significant reduction compared to the healthy controls. Values ranged from 0.47 with Amyloid to 0.94 with Fabrys. Outcome: MCF strongly predicted patient outcomes – and was a more powerful predictor than LVEF (LVEF chi-squared=84 vs MCF chi-squared=160). Conclusion MCF is a complementary measure of cardiac performance to LVEF and equally as logical, intuitive and easy to calculate. It is frequently reduced even when LVEF is normal, and is a much stronger predictor of outcome than LVEF.

A Scoping Review on The Use of Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-Of-Hospital Cardiac Arrest

Aim of the review: To provide an overview of studies that have published data regarding region and population size, procedure location, team composition, inclusion and exclusion criteria, outcome parameters, and cost–benefit analyses on extracorporeal membrane oxygenation use for refractory out-of-hospital cardiac arrest. Data sources: A structured systematic literature search of articles published prior to April 27, 2021, was performed in online databases (PubMed, EMBASE, ClinicalTrials.gov, the EU Clinical Trials Register, and Cochrane Library). Results: Sixty-three articles were included based on predefined eligibility criteria. The included articles were published between 2011 and 2021, with the highest number of articles in 2020 and 2021 (50%). Of the 58 articles that reported data on organisational topics, 47 reported transporting the patients to the hospital for cannulation, 10 reported initiating extracorporeal cardiopulmonary resuscitation (ECPR) on-scene, and one reported doing both. The most common inclusion criterion was a lower age limit of 18 years (in 86% of the articles). Other inclusion criteria were witnessed collapse (67%) and initial ventricular fibrillation/tachycardia (43%), asystole (3%), pulseless electrical activity (5%), pulmonary embolism (2%), and signs of life during CPR (5%). The most common exclusion criterion was a do-not-resuscitate order (38%). Of the 44 studies reporting outcomes, 77% reported survival to hospital discharge and 50%, a cerebral performance category score of 1-2. Other outcome parameters were sparsely reported. Conclusion: There is a variation in regional size, team composition, inclusion and exclusion criteria and reported outcomes. These discrepancies make it challenging to determine how to effectively use ECPR.

Using I135-Xe135 Parent-Daughter Isotopic Activity Ratio for Dating a Recent Nuclear Event

This work focuses on the determination of time zero nuclear events considering the Xe-135/I-135 isotopic activity ratio. Considered as relevant isotopes for CTBT, theses two radionuclides are usable for radioactive release timing. According the considered databases, some parameters namely A, U and F are evaluated taking into account the numerical difference between the radioactive values from nuclear database. We found that these parameters give different values by considering the databases ENDF 2011 and TENDL 2011. These proposed parameters can be used for a quick and accurate evaluation of the nuclear event time and its upper and lower age limits.

Increasing the study of novel anticancer therapies in adolescents: Facilitating adolescent inclusion in adult research.

e13654 Background: Adolescent cancer patients are disproportionately excluded from clinical trials due to trial designs with lower age limits set to the legal age of majority. This has led to a persistent time lag between adult and pediatric approval of new medicines. Publication of new US regulatory guidance encourages inclusion of adolescents in disease- and/or target-appropriate adult trials to facilitate earlier adolescent access to effective therapies. To understand impacts of this and other initiatives fostering adolescent inclusion, a review of recent cancer drug approvals was performed by the ACCELERATE Fostering Age Inclusive Research (FAIR) group. FAIR is an international research collaborative whose aim is to reduce adolescent inequities in access to novel anticancer therapies. Methods: A comprehensive analysis of new oncology drug approvals in Europe (EMA) and the US (FDA) will be conducted. EMA and FDA databases will be interrogated to identify all novel anticancer drug approvals and new use approvals (innovator and generic or biosimilar) between 2018 and 2022. Specific sections of drug labels (Indications and Usage, Dosing and Administration, Use in Specific Populations, Clinical Pharmacology, Clinical studies) will be evaluated. The study team will assess: inclusiveness of the Indication for Use statement; applicability of the approved indication to an adolescent cohort. This analysis will be conducted in sequence: phase 1 analyzes the EMA approvals, phase 2 analyzes the FDA approvals, followed by a comparative analysis across the regions. Phase 1 data are presented using descriptive statistics. Results:. Conclusions: This research evaluating new European drug approvals shows a limited number of anticancer therapies have been adequately studied or approved for adolescent use, even when the approved indication is relevant to adolescents. Recent regulatory guidance to promote the inclusion of adolescents in adult oncology drug trials has not yet led to an increase in adolescent labelling. Increasing awareness of medical oncologists and study sponsors may facilitate cultural mindset change, leading to expansion of eligibility criterion to adolescents and shortening the time lag of adolescent access to novel anticancer therapies. [Table: see text]

Donating a Kidney to a Stranger: Are Healthcare Professionals Facilitating the Journey? Results From the BOUnD Study.

Unspecified kidney donors (UKDs) are approached cautiously by some transplant professionals. The aim of this study was to interrogate the views of UK transplant professionals towards UKDs and identify potential barriers. A purposely designed questionnaire was validated, piloted and distributed amongst transplant professionals at each of the 23 UK transplant centres. Data captured included personal experiences, attitudes towards organ donation, and specific concerns about UKD. 153 responses were obtained, with representation from all UK centres and professional groups. The majority reported a positive experience with UKDs (81.7%; p < 0.001) and were comfortable with UKDs undergoing major surgery (85.7%; p < 0.001). 43.8% reported UKDs to be more time consuming and 52% felt that a mental health assessment should take place before any medical tests. 77% indicated the need for a lower age limit. The suggested age range was broad (16-50years). Adjusted mean acceptance scores did not differ by profession (p = 0.68) but higher volume centres were more accepting (46.2 vs. 52.9; p < 0.001). This is the first quantitative study of acceptance by transplant professionals to a large national UKD programme. Support is broad, however potential barriers to donation have been identified, including lack of training. Unified national guidance is needed to address these.

Visual impairment due to retinopathy of prematurity and concomitant disabilities in the Netherlands

AimDetermine incidence of visual impairment due to retinopathy of prematurity (ROP) and concomitant disabilities between 2009 and 2018 in the Netherlands and compare data to four former similar studies. Secondly, monitor if infants were missed for ROP-screening since the adoption of stricter, risk factor guided criteria (2013). MethodsRetrospective inventory on anonymous data of infants diagnosed with ROP from Dutch visual impairment-institutes. Data including: best corrected visual acuity, ROP-treatment and concomitant disabilities: bronchopulmonary dysplasia, behavioral abnormalities, epilepsy, hearing deficit, developmental delay, cerebral palsy and cerebral visual impairment. During the study period, lower age limit for neonatal life support (2010) and higher oxygen saturation targets (2014) were implemented. ResultsRecords of 53 infants were analyzed. Visual impairment incidence due to ROP was 2.02 per 100.000 live births (2000–2009: 1.84, p = 0.643). Compared to earlier periods (1975–2000), a significant decrease was observed. The incidence of concomitant disabilities remained stable. Mean gestational age (GA) continued to decrease to 26.6 ± 1.9 weeks (2000–2009: 27.4 ± 2.0 weeks, p = 0.047). All patients met the screening inclusion criteria. ConclusionThe incidence of visual impairment due to ROP and concomitant disabilities between 2009 and 2018 has not increased, despite lower GA and higher oxygen saturation targets. None of the infants were missed for ROP screening following introduction of more restricted screening inclusion criteria.

World Health Organization Guideline on the Management of Tuberculosis in Children: Critical Appraisal, Concerns, and Caution.

In September 2022, the World Health Organization (WHO) published a new guideline for the management of tuberculosis (TB) in children and adolescents. It included eight new recommendations. Xpert MTB/RIF Ultra (Xpert Ultra) has been designated as the preferred initial diagnostic test for pulmonary TB and detection of rifampicin resistance. But its place vis-à-vis the previously recommended GeneXpert has not been clarified. Further, the limited diagnostic accuracy of Xpert Ultra in some biological specimens like nasopharyngeal aspirates, and the inability to report the presence or absence of rifampicin resistance in 'trace' reports has not been addressed. The guideline also recommends a shortened 4-mo treatment regimen for non-severe drug-susceptible TB. This is based on a single trial having several methodological issues that limit its applicability and generalizability. Interestingly, the criteria for designating 'non-severe' TB in the trial is based on smear negativity, whereas the new WHO recommendation is to omit smear microscopy altogether. The guideline also recommends an alternative 6-mo intensive regimen for drug-susceptible TB meningitis, which needs more supportive evidence. The lower age limits for the use of bedaquiline and delamanid have been decreased to less than 6 and 3 y respectively. While this makes it feasible to treat drug resistant TB in children with oral medications, the resource implications need careful consideration. These concerns advocate caution before the WHO guideline recommendations can be universally implemented.

Live birth using autologous sperm cryopreserved for 26 years.

We report the successful delivery of a healthy baby after intracytoplasmic sperm injection (ICSI) with frozen-thawed autologous sperm, cryostored for 26 years, the longest successful autologous sperm cryostorage reported. Sperm was cryostored for a 15-year-old boy at the time of his cancer diagnosis. Semen samples were frozen with cryoprotectant, using a graduated vapour-phase nitrogen protocol. Straws were stored in a large vapour-phase nitrogen tank until transfer for use. The couple underwent a single ICSI-in vitro fertilisation procedure using the frozen-thawed sperm with a transfer of five fertilised embryos, resulting in the live birth of a healthy baby boy. This reinforces the importance of offering sperm cryopreservation to men who have not completed their family prior to gonadotoxic treatment for cancer or other diseases. As practical, low-cost fertility insurance, it should be offered to any young man who can collect semen and it provides essentially unlimited duration of fertility preservation. Gonadotoxic chemo or radiotherapy treatment for cancer or other diseases usually causes temporary or permanent male infertility. Sperm cryostorage serves as a practical, low-cost insurance to facilitate future paternity. All men who have not completed their families and are scheduled for gonadotoxic treatments should be offered sperm cryostorage. There is no lower age limit for young men who can collect semen. Sperm cryostorage offers essentially indefinite duration for the preservation of male fertility.

Combining HIPPARCOS and Gaia data for the study of binaries: The BINARYS tool

Context. Orbital motion in binary and planetary systems is the main source of precise stellar and planetary mass measurements, and the joint analysis of data obtained using multiple observational methods can both lift degeneracies and improve precision. Aims. We set out to measure the masses of individual stars in binary systems using all the information brought by the HIPPARCOS and Gaia absolute astrometric missions. Methods. We present BINARYS, a tool that uses the HIPPARCOS and Gaia absolute astrometric data and combines them with relative astrometry and/or radial velocity measurements to determine the orbit of a binary system. This tool rigorously combines the HIPPARCOS and Gaia data (here EDR3) and can use the HIPPARCOS Transit Data as needed for binaries where HIPPARCOS detects significant flux from the secondary component. It also supports the case where Gaia has resolved the system, giving an astrometric solution for both components. Results. We determine model-independent individual masses for the first time for three systems: the two mature binaries Gl 494 (M1 = 0.584 ± 0.003 M⊙ and M2 = 87 ± 1 MJup) and HIP 88745 (M1 = 0.96 ± 0.02 M⊙ and 0.62-0.008+0.009 ), and the younger AB Dor member GJ 2060 (1926-6+7 and 0.882 -0.005+0.004). The latter provides a rare test of evolutionary model predictions at young ages in the low-stellar-mass range and sets a lower age limit of 100 Myr for the moving group.

Inflammation and micronutrient deficiency as major risk factors for anemia in children with intestinal failure:A longitudinal cohort study.

Most data on anemia in children with intestinal failure (IF) have been obtained from studies in which the data were collected at a single point in time. We aimed to identify the frequency of anemia and factors associated with hemoglobin levels in children with IF during their course of home parenteral nutrition. We performed a longitudinal cohort study of patients with IF followed up at a pediatric intestinal rehabilitation center. Outcome variables were hemoglobin levels and prevalence of anemia during the follow-up period. The exposure variables were age, duration of parenteral nutrition, chronic disease, and serum concentrations of C-reactive protein, iron, copper, selenium, vitamins A, D, B12 , and folic acid. Twenty-five children with a median time of receiving parenteral nutrition of 40.7 months were included. A median (and interquartile range) of 40.7 (25.2-58) hemoglobin measurements were performed per patient. Mean (SD) hemoglobin was 10.7 (1.8) g/dL at baseline and 11.6 (0.9) g/dL in the last observation (paired t test, P = 0.07); 32% of patients had mean hemoglobin values below the lower limit for age. In a multivariable predictive model, having C-reactive protein >1 mg/dL was associated with a decrease of 0.57 g/dL in hemoglobin (95% CI, -0.90 to -0.24, P = 0.01), and an increase of 1 mg/L in vitamin A concentration was associated with the increase of 0.93 g/dL in Hb level (95% CI, 0.24-1.61; P = 0.008). Anemia affects almost one-third of children with IF and its frequency decreases during the follow-up period. Hemoglobin levels are associated with inflammatory response and serum micronutrient concentrations.

Triassic Nappe in the Central Part of the Southern Central Asian Orogenic Belt (Ejinaq, NW China): Evidence from Structural Analysis and Geothermochronology

AbstractThe thrust nappe played an important role in the Mesozoic tectonic evolution of the middle part of the Central Asian Orogenic Belt (CAOB). However, the timing, structural style and kinematic processes of the thrust nappe remain controversial, particularly the detail of the thrust nappe in the Guaizihu region (110 km east of Ejinaq). In this study, we investigate new field mapping, seismic sections, geochronology and low‐temperature thermochronometric dating to provide constraints on the history of this thrust nappe in the Chaheilingashun area (northwestern Guaizihu region). The field mapping, seismic sections and structural analysis reveal that the autochthonous system had developed a series of strong fold structures in the upper Permian strata. The allochthonous system mainly contains Devonian monzogranite (U‐Pb age, ranges from 386.7 to 389.0 Ma) and Meso–Neoproterozoic schists (the maximum depositional age, ∼880 Ma), which were thrust upon the upper Permian strata during Middle to Late Triassic. Based on similar rocks, geochronological dating and the Yagan thrust, we suggest that the postulated root zone of this allochthon might have originated from the Huhetaoergai area (40–60 km northwest of the study area). The geochronological results reveal that the lower age limit of this thrust nappe is constrained by the Lower–Middle Triassic syntectonic sediments (tuffaceous sandstone, ∼247 Ma), which is the sedimentary response of the fold structure., The timing of the termination of this thrust nappe is defined by the cooling age (40Ar/39Ar data, 217–211 Ma) of the Devonian monzogranite and Meso–Neoproterozoic schists. Thus, we consider this thrust event in the study area to potentially have occurred in the period from 247 Ma to 211 Ma, which may represent the tectonic response to the closure of the Paleo‐Asian Ocean.