Suppression of black-hole growth by strong outflows at redshifts 5.8-6.6.

Bright quasars, powered by accretion onto billion-solar-mass black holes, already existed at the epoch of reionization, when the Universe was 0.5-1 billion years old1. How these black holes formed in such a short time is the subject of debate, particularly as they lie above the correlation between black-hole mass and galaxy dynamical mass2,3 in the local Universe. What slowed down black-hole growth, leading towards the symbiotic growth observed in the local Universe, and when this process started, has hitherto not been known, although black-hole feedback is a likely driver4. Here we report optical and near-infrared observations of a sample of quasars at redshifts 5.8 ≲ z ≲ 6.6. About half of the quasar spectra reveal broad, blueshifted absorption line troughs, tracing black-hole-driven winds with extreme outflow velocities, up to 17% of the speed of light. The fraction of quasars with such outflow winds at z ≳ 5.8 is ≈2.4 times higher than at z ≈ 2-4. We infer that outflows at z ≳ 5.8 inject large amounts of energy into the interstellar medium and suppress nuclear gas accretion, slowing down black-hole growth. The outflow phase may then mark the beginning of substantial black-hole feedback. The red optical colours of outflow quasars at z ≳ 5.8 indeed suggest that these systems are dusty and may be caught during an initial quenching phase of obscured accretion5.

Evaluation of 'implications for research' statements in systematic reviews of interventions in advanced cancer patients - a meta-research study.

BACKGROUND: Implications for research (IfR) sections are an important part of systematic reviews (SRs) to inform health care researchers and policy makers. PRISMA 2020 recommends reporting IfR, while Cochrane Reviews require a separate chapter on IfR. However, it is unclear to what extent SRs discuss IfR. We aimed i) to assess whether SRs include an IfR statement and ii) to evaluate which elements informed IfR statements. METHODS: We conducted a meta-research study based on SRs of interventions in advanced cancer patients from a previous project (CRD42019134904). As suggested in the Cochrane Handbook, we assessed if the following predefined variables were referred to in IfR statements: patient, intervention, control, outcome (PICO) and study design; concepts underlying Grading of Recommendations, Assessment, Development and Evaluation (GRADE) domains: risk of bias, inconsistency, indirectness, imprecision, publication bias. Data were independently extracted by three reviewers after piloting the data extraction form. Discrepancies were resolved in weekly in-depth discussions. RESULTS: We included 261 SRs. The majority evaluated a pharmacological intervention (n = 244, 93.5%); twenty-nine were Cochrane Reviews (11.1%). Four out of five SRs included an IfR statement (n = 210, 80.5%). IfR statements commonly addressed 'intervention' (n = 121, 57.6%), 'patient ' (n = 113, 53.8%), and 'study design' (n = 107, 51.0%). The most frequent PICO and study design combinations were 'patient and intervention ' (n = 71, 33.8%) and 'patient, intervention and study design ' (n = 34, 16.2%). Concepts underlying GRADE domains were rarely used for informing IfR recommendations: 'risk of bias ' (n = 2, 1.0%), and 'imprecision ' (n = 1, 0.5%), 'inconsistency ' (n = 1, 0.5%). Additional elements informing IfR were considerations on cost effectiveness (n = 9, 4.3%), reporting standards (n = 4, 1.9%), and individual patient data meta-analysis (n = 4, 1.9%). CONCLUSION: Although about 80% of SRs included an IfR statement, the reporting of PICO elements varied across SRs. Concepts underlying GRADE domains were rarely used to derive IfR. Further work needs to assess the generalizability beyond SRs in advanced cancer patients. We suggest that more specific guidance on which and how IfR elements to report in SRs of interventions needs to be developed. Utilizing PICO elements and concepts underlying GRADE according to the Cochrane Handbook to state IfR seems to be a reasonable approach in the interim. REGISTRATION: CRD42019134904.

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]. / Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l'échelle d'imprégnation anticholinergique.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic ¼ drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.

Genome-wide association study to identify genetic loci associated with gastrointestinal nematode resistance in Katahdin sheep.

Resistance to gastrointestinal nematodes has previously been shown to be a moderately heritable trait in some breeds of sheep, but the mechanisms of resistance are not well understood. Selection for resistance currently relies upon faecal egg counts (FEC), blood packed cell volumes and FAMACHA visual indicator scores of anaemia. Identifying genomic markers associated with disease resistance would potentially improve the selection process and provide a more reliable means of classifying and understanding the biology behind resistant and susceptible sheep. A GWAS was conducted to identify possible genetic loci associated with resistance to Haemonchus contortus in Katahdin sheep. Forty animals were selected from the top and bottom 10% of estimated breeding values for FEC from a total pool of 641 sires and ram lambs. Samples were genotyped using Applied Biosystems™ Axiom™ Ovine Genotyping Array (50K) consisting of 51 572 SNPs. Following quality control, 46 268 SNPs were included in subsequent analyses. Analyses were conducted using a linear regression model in plink v1.90 and a single-locus mixed model in snp and variation suite. Genome-wide significance was determined by a Bonferroni correction for multiple testing. Using linear regression, loci on chromosomes 2, 3, 16, 23 and 24 were significantly associated at the genome level with FEC estimated breeding values, and we identified a region on chromosome 2 that was significant using both statistical analyses. We suggest a potential role for the gene DIS3L2 for gastrointestinal nematode resistance in Katahdin sheep, although further research is needed to validate these findings.

The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Novel approach of phosphate-reclamation as struvite from sewage sludge by utilising hydrothermal carbonization.

Hydrothermal carbonization (HTC) showed promising performance as an alternative sewage sludge treatment already, as the draining ability of sludge is improved while fuel properties of the yielded hydrochar are superior to native sludge. On the other hand, the sole combustion of sewage sludge and its corresponding hydrochars are a waste in terms of nutrients like phosphorus and nitrogen. Therefore, a combination of HTC and a nutrient recycling strategy via the precipitation of phosphate and nitrogen as struvite (magnesium ammonium phosphate) are introduced in this research. We used an anaerobically digested sewage sludge with high loads of aluminium- and ironsalts. Phosphate release cannot be reached by HTC alone, as phosphate is heavily bound in stable iron- and aluminium-associations. An acid leaching step removes it from the hydrochar (58.5-94.8% P), while the process liquid arising from HTC is used as ammonium source (107-291 mmol l-1NH4). After adjusting pH and addition of a magnesium source, struvite is rapidly precipitated in high purity. Nitric acid is used as a "catalyst" in HTC to improve the degree of carbonization on one hand but also improve the phosphate recovery on the other hand by increasing the amount of ammonium available for struvite formation in the process liquid. The highest total recovery rate of phosphate from sludge was 82.5 wt.% and therefore this approach showed to be a serious alternative to other P-recovery techniques.

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases.

BACKGROUND: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. METHODS: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. RESULTS: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1­4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1­13) and dose per fraction (median: 18.5 Gy; range 3­37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. CONCLUSION: After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

Elimination of micropollutants by activated carbon produced from fibers taken from wastewater screenings using hydrothermal carbonization.

Activated Carbon (AC) can be used to reduce organic micropollutants (OMPs) in wastewater treatment plants (WWTPs). While producing ACs conventionally still damages the environment, this can be reduced by using renewable raw material from waste streams und producing AC locally. In this study, fibers (toilet paper) were separated out of wastewater by screening WWTP influents in full scale and then used as a no-cost, carbon-rich and heavy metal-poor raw material to produce ACs. Pretreatment was hydrothermal carbonization (HTC). Thereafter, they were activated using KOH to generate activated carbons (HTC-ACs). Their functional groups were characterized using FT-IR, and the alteration of their chemical composition was traced by elementary analysis. Adsorption tests were performed with nitrogen (BET surface) and methylene blue as standard tests. The adsorption capacity was tested with WWTP effluent and the removal of UVA254 as a surrogate for OMP removal was measured. After HTC and activation 13-16% of the fibers dry mass was obtained as HTC-ACs. Higher dehydration and formation of aromatic structures on the HTC-ACs were detected with FT-IR as HTC and activation temperature increased. BET surface and methylene blue adsorption of some HTC-ACs was higher than the Reference AC. Nevertheless, their ability to reduce OMPs is still lower than the Reference AC due to the different nature of their functional groups and their microporous structure that is not fully accessible for OMPs in real wastewater. Further research has to be carried out to adjust the production process so as to obtain mesoporous HTC-ACs tailored to reduce OMP concentrations and to close the carbon loop within WWTPs.

Emotional eating and in vivo norepinephrine transporter availability in obesity: A [11 C]MRB PET pilot study.

OBJECTIVE: Emotional eating (EE) has been linked to norepinephrine dysfunction. Therefore, we aimed to investigate the relationship between EE and norepinephrine transporter (NET) availability. METHOD: Ten severely obese individuals (body mass index (BMI) 42.4 ± 3.7 kg/m2 ) and ten non-obese, healthy controls (BMI 23.9 ± 2.5 kg/m2 ) matched for age and sex were studied using (S,S)-[11 C]-O-methylreboxetine ([11 C]MRB) positron emission tomography (PET). Kinetic modeling of regional tissue time activity curves was performed using multilinear reference tissue model 2 (MRTM2, with the occipital cortex as a reference region) to estimate binding potential based on individual PET-MR coregistration. To test for associations of EE and NET availability, participants completed the EE subscale of the Dutch Eating Behavior Questionnaire before scanning. RESULTS: Obese individuals and non-obese, healthy controls did not significantly differ regarding EE scores and regional NET availability. For obese individuals only, correlative data analyses pointed to a sinoidal distribution pattern as a higher degree of EE related to lower NET availability in the locus coeruleus and to higher NET availability in the left thalamus. DISCUSSION: These results indicate that central in vivo NET availability is altered in EE of individuals with obesity. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:152-156).

Hunger and disinhibition but not cognitive restraint are associated with central norepinephrine transporter availability.

The relationship between food-intake related behaviours measured by the Three-Factor Eating Questionnaire (TFEQ) and in vivo norepinephrine transporter (NET) availability has not been explored yet. We investigated ten obese individuals (body mass index (BMI) 42.4 ± 3.7 kg/m2) and ten normal-weight healthy controls (HC, BMI 23.9 ± 2.5 kg/m2) with (S,S)-[11C]-O-methylreboxetine ([11C]MRB) positron emission tomography (PET). All participants completed the TFEQ, which measures cognitive restraint, disinhibition and hunger. Image analysis required magnetic resonance imaging data sets onto which volumes-of-interests were drawn. Tissue time activity curves (TACs) were obtained from the dynamic PET data followed by kinetic modeling of these regional brain TACs applying the multilinear reference tissue model (2 parameters) with the occipital cortex as reference region. Obese individuals scored significantly higher on the hunger subscale of the TFEQ. Correlative data analysis showed that a higher degree of hunger correlated negatively with the NET availability of the insular cortex in both obese individuals and HC; however, this finding was more pronounced in obesity. Further, for obese individuals, a negative correlation between disinhibition and NET BPND of the locus coeruleus was detected. In conclusion, these initial data provide in vivo imaging support for the involvement of the central NE system in maladaptive eating behaviors such as susceptibility to hunger.

Sex differences in serotonin-hypothalamic connections underpin a diminished sense of emotional well-being with increasing body weight.

BACKGROUND/OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress related to weight remain largely unknown. PARTICIPANTS/METHODS: Here we combined positron emission tomography, using the serotonin transporter (5-HTT) radiotracer [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, with functional connectivity magnetic resonance imaging, the Beck Depression Inventory (BDI-II) and the Impact of Weight on Quality of Life-Lite questionnaire (IWQOL-Lite) to investigate the role of central serotonin in the severity of depression (BDI-II), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). RESULTS: In a group of lean to morbidly obese individuals (n=28), we found sex differences in the 5-HTT availability-related connectivity of the hypothalamus. Males (n=11) presented a strengthened connectivity to the lateral orbitofrontal cortex, whereas in females (n=17) we found strengethened projections to the ventral striatum. Both regions are known as reward regions involved in mediating the emotional response to food. Their resting-state activity correlated positively to the body mass index (BMI) and IWQOL-Lite scores, suggesting that each region in both sexes also underpins a diminished sense of emotional well-being with body weight. Contrarily to males, we found that in females also the BDI-II positively correlated with the BMI and by trend with the activity in ventral striatum, suggesting that in females an increased body weight may convey to other mood dimensions than those weight-related ones included in the IWQOL-Lite. CONCLUSIONS: This study suggests sex differences in serotonin-hypothalamic connections to brain regions of the reward circuitry underpinning a diminished sense of emotional well-being with an increasing body weight.

The central nervous norepinephrine network links a diminished sense of emotional well-being to an increased body weight.

OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress remain largely undiscovered. METHODS: In this pilot study, we combined positron emission tomography, using the norepinephrine transporter (NET) tracer [(11)C]-O-methylreboxetine, with functional connectivity magnetic resonance imaging, the Beck depression inventory (BDI), and the impact of weight on quality of life-Lite questionnaire (IWQOL-Lite), to investigate the role of norepinephrine in the severity of depression (BDI), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). RESULTS: In a small group of lean-to-morbidly obese individuals (n=20), we show that an increased body mass index (BMI) is related to a lowered NET availability within the hypothalamus, known as the brain's homeostatic control site. The hypothalamus displayed a strengthened connectivity in relation to the individual hypothalamic NET availability to the anterior insula/frontal operculum, as well as the medial orbitofrontal cortex, assumed to host the primary and secondary gustatory cortex, respectively (n=19). The resting-state activity in these two regions was correlated positively to the BMI and IWQOL-Lite scores, but not to the BDI, suggesting that the higher the resting-state activity in these regions, and hence the higher the BMI, the stronger the negative impact of the body weight on the individual's emotional well-being was. CONCLUSIONS: This pilot study suggests that the loss in emotional well-being with weight is embedded within the central norepinephrine network.

Single-dose rituximab in refractory lupus nephritis.

BACKGROUND: Off-label use of rituximab in lupus nephritis is reported to be beneficial. While the optimal dose is unknown, the regimen of four intravenous doses of 375 mg/m(2) is commonly employed, despite expense and potential side-effects. AIM: To investigate the response to single-dose rituximab, added to standard corticosteroids plus additional immunosuppressive agent, in refractory lupus nephritis. METHODS: Consecutive consenting patients with refractory lupus nephritis despite steroids plus either cyclophosphamide, mycophenolate or azathioprine were enrolled in this ethics-approved, open-label, prospective study. After baseline assessment, patients received one intravenous infusion of 375 mg/m(2) rituximab. Clinical, biochemical and serological (DsDNA, complement) responses to this dose were analysed. Complete renal response (CR) was defined as normalisation of creatinine, albumin, proteinuria and urinary RBCs and partial response (PR) as ≥50% improvement in at least one parameter, without deterioration in others. B-cell depletion was defined as peripheral CD19 lymphocyte count ≤0.05 × 10(9) /L. RESULTS: Fourteen patients were enrolled in the study. All were B-cell-depleted until 8 months post-dose. Eleven patients (79%) responded (2CR, 9PR) at a median time of 5 months, with a 6-month probability of renal response of 43%. Five patients (45%) relapsed at a median time of 17 months. DsDNA titres decreased in 69%. Side-effects were minimal. CONCLUSIONS: Single-dose rituximab is effective in relapsed/refractory lupus nephritis. Longevity of B-cell depletion with single-dose rituximab is similar to that of four doses with potentially fewer side-effects.

[Availability and integration of palliative medicine at certified lung cancer centers]. / Verfügbarkeit und Integration von Palliativmedizin an zertifizierten Lungenkrebszentren.

BACKGROUND: It is the aim of the certification system for Organ Cancer Centers of the German Cancer Society to ensure that oncology patients receive therapy meeting high quality standards. Lung cancer patients require comprehensive palliative care due to their high symptom load. The purpose of the present study was to identify the existing palliative care structures at 39 certified lung cancer centers. METHODS: The survey tool used was an 18-question questionnaire sent by surface mail to the respective centers. RESULTS: A total of 30 centers took part in the survey. A physician with the additional qualification 'palliative care' was employed at 21 of the centers, a certified palliative care nurse worked at 24 centers. A palliative care unit was available at 9 centers. The cited obstacles to the delivery of palliative care included a shortage of qualified palliative care staff, a lack of refinancing, and the concern that the suggestion of palliative care might cause negative emotions in the respective patients. CONCLUSIONS: Certified lung cancer centers had a wide range of palliative care structures. Openness to and interest in extending existing palliative care services were most commonly identified. A number of serious obstacles in achieving this goal were nevertheless cited.

'Curative' treatments and palliative care: the lack of consensus.

PURPOSE OF REVIEW: A survey was performed to assess whether authors who report about palliative treatments or palliative care share a common understanding of 'curative' treatments. RECENT FINDINGS: Of 107 authors from publications about cancer who used both 'palliative' and 'curative' in the same abstract, 42 (39%) responded. The majority (n=24; 57%) understood 'curative' treatments as 'aimed at complete absence of disease for the rest of life', but 43% (n=18) did not share this view. For example, 19% (n=7) stated that the term describes cancer-directed therapy for prolongation of life or even regardless of the aspired goal. SUMMARY: In the care for cancer patients, unambiguous terminology is essential for the participatory and interdisciplinary decision-making process. Clinicians, researchers and policy makers should be aware of the difference between curative and disease-modifying therapies. Otherwise, this may be a major source of misunderstandings as disease-modifying therapy may be indicated in the incurable stages of the disease as well. In these palliative situations, it is essential to identify the realistic aim(s) of the therapy: prolongation of life, alleviation of suffering or both.

QT interval measurement and correction in patients with atrial flutter: a pilot study.

BACKGROUND AND PURPOSE: Measurement of QT intervals during atrial flutter (AFL) is relevant to monitor the safety of drug delivery. Our aim is to compare QT and QTc intervals in AFL patients before and after catheter ablation in order to validate QT measurement during AFL. METHODS: 25 patients suffering from AFL underwent catheter ablation; 9 were in sinus rhythm and 16 were in AFL at the time of the procedure. Holter ECGs were continuously recorded before, during and after the procedure. In AFL signals, flutter waves were subtracted using a previously-validated deconvolution-based method. Fridericia's QTc was computed before and after ablation after hysteresis reduction. RESULTS: Comparing QTc values obtained before and after ablation showed that (1) the intervention did not significantly affect QTc, and (2) the QTc during AFL was concordant with the QTc value in sinus rhythm. CONCLUSION: QTc can be reliably measured in patients with AFL using flutter wave subtraction and hysteresis reduction.

Brain Charts for the Rhesus Macaque Lifespan.

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Predictors of mortality in Ugandan children with TB, 2016-2021.

BACKGROUND: The burden of pediatric TB is high in Uganda. Our objective was to evaluate predictors of mortality during TB treatment among children at an urban and a rural referral hospital.METHODS: We designed a historical cohort study of TB cases at Mulago National Referral Hospital, Kampala; and Fort Portal Regional Referral Hospital, Fort Portal, Uganda, in children aged <15 years from 2016 to 2021. We used Kaplan-Meier models to estimate survival and fit multivariable Cox regression models to determine mortality hazards during TB treatment.RESULTS: We identified 1,658 children diagnosed with TB from 2016 to 2021. Of 1,623 children with known treatment outcomes, 127/1,623 (7.8%) died during TB treatment, 1,298/1,623 (78.3%) completed treatment, 150/1,623 (9.2%) were lost to follow-up, and two children failed treatment. Using Kaplan-Meier functions, the median time to death was 27 days following treatment initiation. In adjusted Cox models, predictors of mortality included HIV (aHR 1.68, 95% CI 1.01-2.81), moderate malnutrition (aHR 2.22, 95% CI 1.18-4.16), and severe malnutrition (aHR 2.92, 95% CI 1.75-4.87).CONCLUSION: Mortality was high at an urban and a rural referral hospital among children who initiated TB treatment from 2016 to 2021, with the majority of deaths occurring during the intensive phase of TB treatment. Malnutrition and HIV were significant predictors of death during treatment.