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Purpose: The recently introduced Pipeline Vantage Embolization Device with Shield Technology is the fourth generation of Pipeline flow diverter devices. Due to the relatively high rate of intraprocedural technical complications, modifications were subsequently made to the device after a limited release of the device in 2020. This study aimed to evaluate the safety and efficacy of the modified version of this device., Methods: This was a multicentre retrospective series. The primary efficacy endpoint was aneurysm occlusion in the absence of retreatment. The primary safety endpoint was any neurological morbidity or death. Ruptured and unruptured aneurysms were included in the study., Results: A total of 52 procedures were performed for 60 target aneurysms. Treatment was performed on 5 patients with ruptured aneurysms. The technical success rate was 98%. The mean clinical follow-up time was 5.5 months. In patients presenting with unruptured aneurysms there were no deaths, 3 (6.4%) major complications and 7 (13%) minor complications. In the five patients presenting with subarachnoid haemorrhage there were 2 (40%) major complications with 1 (20%) of these resulting in death, and 1 (20%) minor complication. Of the patients 29 (56%) had undergone 6‑monthly postprocedural angiographic imaging with a mean time of 6.6 months demonstrating that 83% of patients had achieved adequate occlusion (RROC1/2) of the aneurysm., Conclusions: In this non-industry-sponsored study, the occlusion rates and safety outcomes were similar to those seen in previously published studies with flow diverter devices and earlier generation Pipeline devices. Modifications to the device appear to have improved ease of deployment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The Pipeline Vantage Embolization Device (PEDV) is the fourth-generation pipeline flow diverter for intracranial aneurysm treatment. There are no outcome studies for the second PEDV version. We aimed to evaluate safety and efficacy outcomes. Primary and secondary objectives were to determine outcomes for unruptured and ruptured cohorts, respectively., Methods: In this multicenter retrospective and prospective study, we analyzed outcome data from eight centers using core laboratory assessments. We determined 30-day and ≥3-month mortality and morbidity rates, and 6- and 18-month radiographic aneurysm occlusion rates for procedures performed during the period July 2021-March 2023., Results: We included 121 consecutive patients with 131 aneurysms. The adequate occlusion rate for the unruptured cohort at short-term and medium-term follow up, and also for the ruptured cohort at short-term follow up, was >90%. Two aneurysms (1.5%) underwent retreatment. When mortality attributed to a palliative case in the unruptured cohort, or subarachnoid hemorrhage in the ruptured cohort, was excluded then the overall major adverse event rate in respective cohorts was 7.5% and 23.5%, with 0% mortality rates for each. When all event causes were included on an intention-to-treat basis, the major adverse event rates in respective cohorts were 8.3% and 40.9%, with 0.9% and 22.7% mortality rates., Conclusions: For unruptured aneurysm treatment, the second PEDV version appears to have a superior efficacy and similar safety profile to previous-generation PEDs. These are acceptable outcomes in this pragmatic and non-industry-sponsored study. Analysis of ruptured aneurysm outcomes is limited by cohort size. Further prospective studies, particularly for ruptured aneurysms, are needed., Competing Interests: Competing interests: Microvention core laboratory for neurointerventional study: payment to TCB. Siemens Healthineers Speakers Bureau Educational lecture on brain tumours, not related to aneurysms: payment to TCB. Medtronic Speakers Bureau Educational lecture on an independent non-industry-sponsored study published in AJNR 2019 on Pipeline Flow Diverter device: payment to TCB. Bayer Speakers Bureau Educational lecture on Explainability in AI, not related to aneurysms: payment to TCB. Consulting and proctoring agreement with Medtronic, Stryker, Balt, and Cerenovus: payment to TP. Microvention, Balt, and Medtronic support to attend meetings: payment to TM., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Context: Although sleep disordered breathing (SDB) is well-recognised in acromegaly, most studies have reported heterogeneous, often heavily treated, groups and few have performed detailed sleep phenotyping at presentation., Objective: To study SDB using the gold standard of polysomnography, in the largest group of newly-diagnosed, treatment-naïve patients with acromegaly., Setting and Patients: 40 patients [22 males, 18 females; mean age 54 years (range 23-78)], were studied to: (i) establish the prevalence and severity of SDB (ii) assess the reliability of commonly employed screening tools [Epworth Sleepiness Scale (ESS) and overnight oxygen desaturation index (DI)] to detect SDB (iii) determine the extent to which sleep architecture is disrupted., Results: Obstructive sleep apnoea (OSA), defined by the apnoea-hypopnoea index (AHI), was present in 79% of subjects (mild, n = 12; moderate, n = 5; severe, n = 14). However, in these individuals with OSA by AHI criteria, ESS (positive in 35% [n = 11]) and DI (positive in 71%: mild, n = 11; moderate, n = 6; severe, n = 5) markedly underestimated its prevalence/extent. Seventy-eight percent of patients exhibited increased arousal, with marked disruption of the sleep cycle, despite most (82%) having normal total time asleep. Fourteen patients spent longer in stage 1 sleep. Deeper sleep stages were severely attenuated in many subjects (reduced stage 2, n = 18; reduced slow wave sleep, n = 24; reduced rapid eye movement sleep, n = 32)., Conclusion: Our study provides strong support for clinical guidelines that recommend screening for sleep apnoea syndrome in patients with newly-diagnosed acromegaly. Importantly, however, it highlights shortcomings in commonly recommended screening tools (questionnaires, desaturation index) and demonstrates the added value of polysomnography to allow timely detection of obstructive sleep apnoea and associated sleep cycle disruption., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Process Mining is a technique looking into the analysis and mining of existing process flow. On the other hand, Machine Learning is a data science field and a sub-branch of Artificial Intelligence with the main purpose of replicating human behavior through algorithms. The separate application of Process Mining and Machine Learning for healthcare purposes has been widely explored with a various number of published works discussing their use. However, the simultaneous application of Process Mining and Machine Learning algorithms is still a growing field with ongoing studies on its application. This paper proposes a feasible framework where Process Mining and Machine Learning can be used in combination within the healthcare environment.

A previously independent 82-year-old woman presented with 5 months of worsening confusion, mobility and cognitive decline, with deficits in orientation, language and executive function. A cerebral dural arteriovenous fistula was identified and successfully embolised, after which her cognitive ability and independence dramatically improved. Although rare, a dural arteriovenous fistula may mimic a rapidly progressive dementia, but its early recognition and treatment can completely reverse the dementia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Image registration is an inherently ill-posed problem that lacks the constraints needed for a unique mapping between voxels of the two images being registered. As such, one must regularize the registration to achieve physically meaningful transforms. The regularization penalty is usually a function of derivatives of the displacement-vector field and can be calculated either analytically or numerically. The numerical approach, however, is computationally expensive depending on the image size, and therefore a computationally efficient analytical framework has been developed. Using cubic B-splines as the registration transform, we develop a generalized mathematical framework that supports five distinct regularizers: diffusion, curvature, linear elastic, third-order, and total displacement. We validate our approach by comparing each with its numerical counterpart in terms of accuracy. We also provide benchmarking results showing that the analytic solutions run significantly faster-up to two orders of magnitude-than finite differencing based numerical implementations., (© 2021 IOP Publishing Ltd.)

Rare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson's disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments.

Background: Surgical clipping of intracranial aneurysms is typically robust and durable. However, residual aneurysmal components may be seen after clipping. Furthermore, there may be occasional aneurysmal recurrence. These factors are both clinically relevant because subarachnoid hemorrhage after clipping is a rare but important event. The rationale for any treatment is to substantially decrease the future risk of hemorrhage. Small series have shown coiling as a retreatment strategy after unsuccessful clipping, but none has explored the feasibility of Woven Endobridge (WEB) implantation., Case Description: We examined the feasibility of WEB implantation as second-line treatment for wide-necked residual aneurysms after unsuccessful clipping. We also recorded the safety and efficacy in this small series of 6 patients. To determine safety, we measured the modified Rankin Scale score before and after the procedure, and at 2 later time points (mean follow-up, 5 months and 15 months). To determine efficacy, we obtained radiographic aneurysm occlusion outcomes (including WEB Occlusion Scale) at these 2 time points. Four middle cerebral artery and 2 anterior communicating artery complex aneurysms were treated with WEB implantation, showing feasibility in 6/6 cases (100%). Follow-up at 15 months showed no change from preprocedural modified Rankin Scale score and there were no other complications. There was adequate occlusion in 5/6 cases (83%)., Conclusions: WEB implantation provided a feasible option in this challenging retreatment scenario. This is a small series and prospective data are required to make outcome inferences for this population. Nonetheless, we observed no complications and high adequate occlusion rates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: The recently introduced Pipeline Flex Embolization Device with Shield Technology (Pipeline Shield) is the third generation of Pipeline flow-diverter devices. It has a new stent-surface modification, which reduces thrombogenicity. We aimed to evaluate clinical and radiographic (safety and efficacy) outcomes of the Pipeline Shield., Materials and Methods: The 30-day and 1-year mortality and morbidity rates and the 6- and 18-month radiographic aneurysm occlusion outcomes for procedures performed between March 2016 and January 2018 were analyzed. 3D-TOF-MRA was used for follow-up., Results: Forty-four attempted Pipeline Shield procedures were performed for 41 patients with 44 target aneurysms (total of 52 aneurysms treated). A total of 88.5% of devices were inserted in the anterior circulation, and 11.5%, in the posterior circulation; 49/52 (94.2%) aneurysms were saccular; and 1/52 (1.9%) was fusiform. One (1.9%) aneurysm was an iatrogenic pseudoaneurysm, and 1 (1.9%) was a dissecting aneurysm. Seventy-one percent (35/49) of the saccular aneurysms were wide-neck (neck, >4 mm), 34.6% (18/52) were large (≥10 mm), and 3.8% (2/52) were giant (≥25 mm). The mean aneurysm sac maximal diameter was 9.0 mm, and the mean neck width was 5.0 mm. The cumulative mortality and morbidity rates were 2.3% and 6.8% at 1 year, respectively. The adequate occlusion rate was 78.8% at 6 months and 90.3% at 18 months., Conclusions: In this pragmatic and non-industry-sponsored study, the occlusion rates and safety outcomes were similar to those seen in previously published studies with flow-diverter devices and earlier generation Pipeline Embolization Devices., (© 2019 by American Journal of Neuroradiology.)

Atypical parkinsonian disorders (APDs) comprise a group of neurodegenerative diseases with heterogeneous clinical and pathological features. Most APDs are sporadic, but rare familial forms have also been reported. Epidemiological and post-mortem studies associated APDs with oxidative stress and cellular protein aggregates. Identifying molecular mechanisms that translate stress into toxic protein aggregation and neurodegeneration in APDs is an active area of research. Recently, ribonucleic acid (RNA) stress granule (SG) pathways were discussed to be pathogenically relevant in several neurodegenerative disorders including APDs. Using whole genome sequencing, mRNA expression analysis, transfection assays and cell imaging, we investigated the genetic and molecular basis of a familial neurodegenerative atypical parkinsonian disorder. We investigated a family with six living members in two generations exhibiting clinical symptoms consistent with atypical parkinsonism. Two affected family members suffered from parkinsonism that was associated with ataxia. Magnetic resonance imaging (MRI) of these patients showed brainstem and cerebellar atrophy. Whole genome sequencing identified a heterozygous stop-gain variant (c.C811T; p.R271X) in the Poly(A) binding protein, cytoplasmic 4-like (PABPC4L) gene, which co-segregated with the disease in the family. In situ hybridization showed that the murine pabpc4l is expressed in several brain regions and in particular in the cerebellum and brainstem. To determine the functional impact of the stop-gain variant in the PABPC4L gene, we investigated the subcellular localization of PABPC4L in heterologous cells. Wild-type PABPC4L protein localized predominantly to the cell nucleus, in contrast to the truncated protein encoded by the stop-gain variant p.R271X, which was found homogeneously throughout the cell. Interestingly, the wild-type, but not the truncated protein localized to RasGAP SH3 domain Binding Protein (G3BP)-labeled cytoplasmic granules in response to oxidative stress induction. This suggests that the PABPC4L variant alters intracellular distribution and possibly the stress granule associated function of the protein, which may underlie APD in this family. In conclusion, we present genetic and molecular evidence supporting the role of a stop-gain PABPC4L variant in a rare familial APD. Our data shows that the variant results in cellular mislocalization and inability of the protein to associate with stress granules.

A flower like cobalt oxide nanostructured thin film (Co2O3) on Nickel (Ni) plate as have been successfully developed via alcoholic Seed Layer assisted chemical bath Deposition (SLD) process. Through the controlled alkaline electrolytes, the flower and paddles like Co2O3 nanoarchitectures were formed. The prepared thin film was characterized by X-ray diffraction (XRD), scanning electron microscope with energy dispersive X-ray (SEM and EDX), Atomic Force Microscope (AFM), Raman spectroscopy techniques. Electron micrograph reveals the flower and paddles like nanostructured Co2O3 thin film deposited on Ni plates. The electrochemical characteristics were investigated using cyclic voltammetry (CV), charge-discharge and AC impedance spectroscopy in different aqueous electrolytes such as NaOH, KOH, and LiOH. The maximum specific capacitance of 856 Fg-1 was attained with 2 M KOH electrolyte with 2 mVs-1 of the Co2O3 thin film coated Ni plate at 80 °C using SLD method. The capacitance values obtained with various electrolytes are in the order of KOH > NaOH > LiOH. The results indicate that the present method is economical and the material is ecofriendly with enhanced capacitance property.

Background: The introduction of flow-diverting stents in the last decade provides an alternative endovascular treatment choice in selected intracranial aneurysms. This retrospective analysis of a UK centre's experience provides insight into clinical and radiographic outcomes., Methods: Electronic patient records, diagnostic and procedural images and written procedural records for patients treated with the PED between August 2009 and April 2014 were reviewed. Follow-up TOF MRA was performed after treatment. Clinical and radiographic outcomes were analyzed and compared with other PED studies., Results: Twenty-nine patients with 30 attempted PED treatments were reviewed representing 3.5% of the treated aneurysm patient cohort. 63.6% (21/33) of the aneurysms were wide-necked (>4 mm), 60.6% (20/33) were large or giant (≥10 mm). The mean aneurysm sac diameter was 12.0 mm; the mean neck width was 4.5 mm. Mortality and morbidity rates were 3.3% and 10.0%, respectively. The total adequate occlusion rate was 78.1% (25/32) at 18 months. The neck width of aneurysms with residual sac filling and complete occlusion differed significantly (p = 0.04)., Conclusions: Highly selected aneurysms treated with a PED in a UK centre have similar occlusion and complication rates when compared to non-UK studies. Again, it appeared that delayed aneurysm rupture remained a risk for PED treatment in large or giant aneurysms. Follow-up with TOF MRA gave similar occlusion results compared to those obtained with DSA in other studies. The influence of neck size on occlusion rate should be examined in future PED studies.

Background and Objective: Modern sulfonylureas like glimepiride offer effective glycemic control with extrapancreatic benefits and good tolerability. The objective of the present study was to evaluate and compare safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus (T2DM)., Methods: In this open-label, randomized, comparative, multicenter study, a total of 305 T2DM patients who were either drug naïve or uncontrolled on metformin were randomized to glimepiride 1 or 2 mg/sustained-release metformin 1000 mg once daily (glimepiride group, n = 202) or sitagliptin 50 mg/metformin 500 mg twice daily (sitagliptin group, n = 103) for 12 weeks. Primary endpoint was change in glycosylated hemoglobin (HbA1c). Secondary endpoints were change in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body mass index (BMI) and to assess overall safety profile., Results: At 12 weeks, there was a statistically significant difference in the mean HbA1c reduction in glimepiride group (0.42%) as compared to sitagliptin group (0.30%) ( P = 0.001). Mean reduction in FPG and PPG was also statistically significant in the glimepiride group as compared to the sitagliptin group ( P = 0.008). There was no significant difference in terms of change in BMI (0.07 ± 0.39 kg/m 2 vs. 0.08 ± 0.31 kg/m 2 ) in glimepiride and sitagliptin groups, respectively, ( P = 0.644) between both the groups. The incidences of hypoglycemic events were also comparable among both the groups., Conclusion: In T2DM patients, glimepiride/metformin combination exhibited significant reduction in glycemic parameters as compared to sitagliptin/metformin combination. Moreover, there was no significant difference between both the groups in terms of change in BMI and incidence of hypoglycemia., Competing Interests: There are no conflicts of interest.

This article draws on grounded qualitative research with rural Tamil women who acquired a disability during the civil war in Sri Lanka and conceptualizes an intersectionality-peace framework. Three main themes were developed from the interviews: narratives of conflict, survival outcomes of social assistance and mobilization of cross-ethnic relationships. With the support of a local women's disability advocacy organization, Tamil women with disabilities were enabled to overcome social stigma and claim a positive identity as women with disabilities. The organization's focus on realizing disability rights created new opportunities for these highly marginalized rural women. The women were also supported to form cross-ethnic relationships with women who similarly faced multiple oppressions. These relationships transformed the women into 'agents of peace', using their newfound disability identity to foster cross-ethnic dialogue and create safe spaces in the post-conflict context.

Objective: To determine if functional imaging using 11 C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment., Design/methods: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied., Results: Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS., Conclusions: In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy)., (© 2016 European Society of Endocrinology.)

Interoception is the sensing of physiological signals originating inside the body, such as hunger, pain and heart rate. People with greater sensitivity to interoceptive signals, as measured by, for example, tests of heart beat detection, perform better in laboratory studies of risky decision-making. However, there has been little field work to determine if interoceptive sensitivity contributes to success in real-world, high-stakes risk taking. Here, we report on a study in which we quantified heartbeat detection skills in a group of financial traders working on a London trading floor. We found that traders are better able to perceive their own heartbeats than matched controls from the non-trading population. Moreover, the interoceptive ability of traders predicted their relative profitability, and strikingly, how long they survived in the financial markets. Our results suggest that signals from the body - the gut feelings of financial lore - contribute to success in the markets.

Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Although the majority of childhood ACC arises in the context of inherited cancer susceptibility syndromes, it remains less clear whether a hereditary tumor predisposition exists for the development of ACC in adults. Here, we report the first occurrence of familial ACC in a kindred with Lynch syndrome resulting from a pathogenic germline MSH2 mutation., Case: A 54-year-old female with a history of ovarian and colorectal malignancy was found to have an ACC. A detailed family history revealed her mother had died of ACC and her sister had previously been diagnosed with endometrial and colorectal cancers. A unifying diagnosis of Lynch syndrome was considered, and immunohistochemical analyses demonstrated loss of MSH2 and MSH6 expression in both AACs (proband and her mother) and in the endometrial carcinoma of her sister. Subsequent genetic screening confirmed the presence of a germline MSH2 mutation (resulting in deletions of exons 1-3) in the proband and her sister., Conclusion: Our findings provide strong support for the recent proposal that ACC should be considered a Lynch syndrome-associated tumor and included in the Amsterdam II clinical diagnostic criteria. We also suggest that screening for ACC should be considered in cancer surveillance strategies directed at individuals with germline mutations in DNA mismatch repair genes.

Background: This review critically addresses the putative molecular targets of Diabetic Nephropathy (DN) and screens effective phytocompounds that can be therapeutically beneficial, and highlights their mechanistic modalities of action., Introduction: DN has become one of the most prevalent complications of clinical hyperglycemia, with individual-specific variations in the disease spectrum that leads to fatal consequences. Diverse etiologies involving oxidative and nitrosative stress, activation of polyol pathway, inflammasome formation, Extracellular Matrix (ECM) modifications, fibrosis, and change in dynamics of podocyte functional and mesangial cell proliferation adds up to the clinical complexity of DN. Current synthetic therapeutics lacks target-specific approach, and is associated with the development of inevitable residual toxicity and drug resistance. Phytocompounds provides a vast diversity of novel compounds that can become an alternative therapeutic approach to combat the DN., Methods: Relevant publications were searched and screened from research databases like GOOGLE SCHOLAR, PUBMED and SCISEARCH. Out of 4895 publications, the most relevant publications were selected and included in this article., Result: This study critically reviews over 60 most promising phytochemical and provides with their molecular targets, that can be of pharmacological significance in context to current treatment and concomitant research in DN., Conclusion: This review highlights those most promising phytocompounds that have the potential of becoming new safer naturally-sourced therapeutic candidates and demands further attention at clinical level., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Myricetin is a natural flavonoid used in various health management systems. In this present study myricetin tested to evaluate the effect on lipids and lipid metabolism enzymes in normal and streptozotocin (STZ) with cadmium (Cd) induced diabetic nephrotoxic rats. Diabetic nephrotoxic rats were significantly (P<0.05) increased the levels of urinary albumin and lipid profiles: total cholesterol (TC), triglycerides (TGs), free fatty acids (FFAs), phospholipids (PLs), low density lipoprotein (LDL), very low-density lipoproteins (VLDL), and decreased in the levels of high-density lipoproteins (HDL). In addition, the activity of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were decreased significantly, whereas the 3-hydroxy 3-methylglutaryl coenzyme A (HmgCoA) reductase activity was increased. The upregulation of sterol regulatory element binding protein-1a (SREBP-1a), SREBP-1c, SREBP-2, transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF) and downregulation peroxisome proliferator-activated receptor alpha (PPAR-α) proteins expression levels were noticed. An administration of myricetin (1.0 mg/kg body weight (b/w)) for 12 weeks was brought the above parameters towards normal level. Histopathological study of kidney samples showed that extracellular mesangial matrix expansion, glomerulosclerosis and interstitial fibrosis in diabetic nephrotoxic rats was suppressed by myricetin treatment. Further our results indicate that administration of myricetin afforded remarkable protection against STZ-Cd induced alterations in lipid metabolism and thereby reduced the diabetic nephropathy in experimental rats., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Risk taking is central to human activity. Consequently, it lies at the focal point of behavioral sciences such as neuroscience, economics, and finance. Many influential models from these sciences assume that financial risk preferences form a stable trait. Is this assumption justified and, if not, what causes the appetite for risk to fluctuate? We have previously found that traders experience a sustained increase in the stress hormone cortisol when the amount of uncertainty, in the form of market volatility, increases. Here we ask whether these elevated cortisol levels shift risk preferences. Using a double-blind, placebo-controlled, cross-over protocol we raised cortisol levels in volunteers over 8 d to the same extent previously observed in traders. We then tested for the utility and probability weighting functions underlying their risk taking and found that participants became more risk-averse. We also observed that the weighting of probabilities became more distorted among men relative to women. These results suggest that risk preferences are highly dynamic. Specifically, the stress response calibrates risk taking to our circumstances, reducing it in times of prolonged uncertainty, such as a financial crisis. Physiology-induced shifts in risk preferences may thus be an underappreciated cause of market instability.

Background: Multimodal CT or MR imaging may be helpful in guiding reperfusion therapy for stroke. However, access to multimodal imaging may frequently be limited. We hypothesised that certain clinical and non-enhanced CT (NECT) findings at initial assessment can potentially predict mismatch on CT perfusion (CTP) in patients with acute ischaemic stroke., Methods: We undertook an analysis of prospectively collected clinical and imaging data of consecutive patients with anterior circulation ischaemic stroke who underwent CTP during their initial assessment. NECT was read for early ischaemic change as measured by the Alberta Stroke Program Early CT Score (ASPECTS), and for hyperdense middle cerebral artery sign (HMCAS). CTP images were evaluated for mismatch. Independent clinical and imaging predictors of a CTP mismatch were identified using stepwise logistic regression., Results: Of the 202 patients, 92 (46%) demonstrated a mismatch, 23 (11%) a matched deficit, and 87 (43%) no perfusion deficit. HMCAS on NECT (OR 13.65, 95% CI 6.04-30.81, p<0.001), female gender (OR 2.37, 95% CI 1.19-4.72, p = 0.015), atrial fibrillation (OR 2.05, 95% CI 1.02-4.11, p = 0.044), and absence of a history of hypertension (OR 0.46, 95% CI 0.22-0.96, p = 0.037) were independent predictors of a CTP mismatch. HMCAS had 58% sensitivity, 91% specificity, 84% positive predictive value and 72% negative predictive value., Conclusions: A HMCAS on the initial NECT is associated with a high probability of mismatch in acute ischaemic stroke, and may identify patients most likely to benefit from recanalisation treatments when access to multimodal CT or MR facilities is limited., (© 2013 Elsevier B.V. All rights reserved.)

Objective: To develop an alternative method to immunoassay for the quantitative analysis of insulin-like growth factor 1 (IGF-1) using a mass spectrometry (MS)-based approach., Study Design and Patients: A stable isotope dilution Ultra High Performance Liquid Chromatography tandem MS (uHPLC-MS/MS)-based method for the quantification of IGF-1 was developed. The method employed Selected Reaction Monitoring (SRM) of two tryptic peptides derived from IGF-1, and utilised solid phase extraction for enrichment of the peptide fraction containing IGF-1 rather than immunocapture, so was less susceptible to assay interference. Plasma samples from 25 consecutive unselected patients with newly diagnosed acromegaly, collected both before and after 24 weeks of primary medical therapy with Lanreotide Autogel(®), were analysed by a widely used commercial immunoassay (Siemens Immulite 2000(®)) and by uHPLC-MS/MS., Results: The uHPLC-MS/MS method showed good correlation with the immunoassay over a wide range of IGF-1 concentrations. The Passing and Bablock regression was: uHPLC-MS/MS (nmol/l) = 1.37 (95% confidence interval: 1.26-1.46) × immunoassay (nmol/l) + 3.14 (95% confidence interval: -2.71 to 10.32). Six patients had discordant growth hormone (GH) and IGF-1 levels following primary medical therapy, and in all six the immunoassay and uHPLC-MS/MS platforms returned comparable results. The method was not affected by concentrations of IGFBP3 up to 12,500 ng/ml., Conclusions: uHPLC-MS/MS offers an independent method for determining/validating IGF-1 in subjects with acromegaly. Further studies, including the establishment of age- and sex-matched reference ranges and calibration to the new International IGF-1 standard IS 02/254, are now required to allow its introduction in to routine clinical use., (© 2012 Blackwell Publishing Ltd.)

Context: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management., Objective: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort., Study Design: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy., Results: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 μg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged., Conclusions: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.

Glioblastoma is a highly aggressive tumour with marked heterogeneity at the morphological level in both the tumour cells and the associated highly prominent vasculature. As we begin to develop an increased biological insight into the underlying processes driving the disease, fewer attempts have thus far been made to understand these phenotypic differences. We sought to address this by carefully assessing the morphological characteristics of both the tumour cells and the associated vasculature, relating these observations to the IDH1/MGMT status, with a particular focus on the early onset population of young adults who develop primary glioblastoma. 276 primary glioblastoma specimens were classified into their predominant cell morphological type (fibrillary, gemistocytic, giant cell, small cell, oligodendroglial, sarcomatous), and assessed for specific tumour (cellularity, necrosis, palisades) and vascular features (glomeruloid structures, arcades, pericyte proliferation). IDH1 positive glioblastomas were associated with a younger age at diagnosis, better clinical outcome, prominent oligodendroglial and small cell tumour cell morphology, pallisading necrosis and glomeruloid vascular proliferation in the absence of arcade-like structures. These features widen the phenotype of IDH1 mutation-positive primary glioblastoma in young adults and provide correlative evidence for a functional role of mutant IDH1 in the differential nature of neo-angiogenesis in different subtypes of glioblastoma.

Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.

Objective: To describe a case illustrating the use of sitagliptin, an inhibitor of dipeptidyl-peptidase-4 (DPP-4), in anti-glutamic acid decarboxylase antibody-positive diabetes mellitus in association with a rare ataxic variant of stiff person syndrome., Methods: We present our experience with use of the DPP-4 inhibitor sitagliptin for management of autoimmune diabetes in a elderly woman and highlight the association of diabetes with other autoimmune conditions., Results: A 68-year-old Japanese woman presented with poorly controlled "type 2" diabetes mellitus, cerebral palsy, cerebellar ataxia, and hypothyroidism. She complained of stiffness and spasms, which had resulted in multiple falls and immobility. Antidiabetic medications included gliclazide, rosiglitazone, and acarbose; various insulins had been tried but discontinued because they worsened her stiffness and spasms. Her hemoglobin A1c values remained above 9% despite maximal doses of the aforementioned orally administered hypoglycemic agents. After sitagliptin therapy was initiated, her hemoglobin A1c level decreased from 9.3% (78 mmol/mol) to 7.3% (56 mmol/mol) in 5 months. Investigations confirmed the presence of an ataxic variant of stiff person syndrome. On repeated testing 18 months later, her anti-glutamic acid decarboxylase antibody levels had declined by more than 85%., Conclusion: Apart from the well-known mechanism of an increase in glucagonlike peptide-1, sitagliptin may exert its glucose-lowering effect by other mechanisms in patients with autoimmune diabetes. Further studies should be undertaken to address the effectiveness of DPP-4 inhibitors in non-type 2 diabetes.

Introduction: A total of 17 cases of penetrating neck injury were managed by the otolaryngology team at King's College Hospital over a 3-year period in the 1980s. In April 2010 King's College Hospital became the major trauma centre for South East London. This prospective cohort study compares the incidence, changing demographic features and treatment outcomes of penetrating neck trauma in South East London over the previous 23 years., Methods: Data were collected over a 12-month period (April 2010 to March 2011) and a selective management protocol was introduced to standardise initial investigations and further treatment., Results: The past 23 years have seen a 550% increase in the incidence of penetrating neck injuries in South East London, with a marked increase in gun crime. Only 38% of cases underwent negative neck exploration in 2011 compared with 65% in 1987. Selective conservative management based on the absence of haemodynamic instability or radiological findings reduces length of hospital stay, lightens surgical workload and cuts costs without affecting morbidity or mortality., Conclusions: The increased incidence of penetrating neck injury is a reflection of more interpersonal violence rather than a consequence of the larger South East London trauma centre catchment area. Tackling this problem requires focus on wider issues of community prevention. Sharing of data between the four London trauma centres and the police is needed to help prevent interpersonal violence and develop a universal treatment algorithm for other institutions to follow.

The sequence specificity of the anti-tumour drug, cisplatin, was determined in a DNA sequence that contained seven telomeric repeats and a run of ten consecutive guanine bases. Cisplatin preferentially forms DNA adducts at consecutive guanine sequences. Hence these DNA sequences were examined in order to gain an insight into the important human genomic regions that are damaged by cisplatin. A polymerase stop/linear amplification assay was employed with an automated DNA capillary sequencer and laser-induced fluorescence detection to quantitatively determine the DNA sequence specificity of cisplatin in a plasmid clone containing seven telomeric repeats and a sequence of ten consecutive guanine bases. It was found that cisplatin preferentially damaged the ten consecutive guanine sequence although the telomeric DNA sequences were also a major site of cisplatin adduct formation.

Image registration is inherently ill-posed, and lacks a unique solution. In the context of medical applications, it is desirable to avoid solutions that describe physically unsound deformations within the patient anatomy. Among the accepted methods of regularizing non-rigid image registration to provide solutions applicable to medical practice is the penalty of thin-plate bending energy. In this paper, we develop an exact, analytic method for computing the bending energy of a three-dimensional B-spline deformation field as a quadratic matrix operation on the spline coefficient values. Results presented on ten thoracic case studies indicate the analytic solution is between 61-1371x faster than a numerical central differencing solution.

Introduction: Pendred syndrome, a combination of sensorineural deafness, impaired organification of iodide in the thyroid and goitre, results from biallelic defects in pendrin (encoded by SLC26A4), which transports chloride and iodide in the inner ear and thyroid respectively. Recently, pendrin has also been identified in the kidneys, where it is found in the apical plasma membrane of non-α-type intercalated cells of the cortical collecting duct. Here, it functions as a chloride-bicarbonate exchanger, capable of secreting bicarbonate into the urine. Despite this function, patients with Pendred syndrome have not been reported to develop any significant acid-base disturbances, except a single previous reported case of metabolic alkalosis in the context of Pendred syndrome in a child started on a diuretic., Case Report: We describe a 46-year-old female with sensorineural deafness and hypothyroidism, who presented with severe hypokalaemic metabolic alkalosis during inter-current illnesses on two occasions, and who was found to be homozygous for a loss-of-function mutation (V138F) in SLC26A4. Her acid-base status and electrolytes were unremarkable when she was well., Conclusion: This case illustrates that, although pendrin is not usually required to maintain acid-base homeostasis under ambient condition, loss of renal bicarbonate excretion by pendrin during a metabolic alkalotic challenge may contribute to life-threatening acid-base disturbances in patients with Pendred syndrome.

Spline-based deformable registration methods are quite popular within the medical-imaging community due to their flexibility and robustness. However, they require a large amount of computing time to obtain adequate results. This paper makes two contributions towards accelerating B-spline-based registration. First, we propose a grid-alignment scheme and associated data structures that greatly reduce the complexity of the registration algorithm. Based on this grid-alignment scheme, we then develop highly data parallel designs for B-spline registration within the stream-processing model, suitable for implementation on multi-core processors such as graphics processing units (GPUs). Particular attention is focused on an optimal method for performing analytic gradient computations in a data parallel fashion. CPU and GPU versions are validated for execution time and registration quality. Performance results on large images show that our GPU algorithm achieves a speedup of 15 times over the single-threaded CPU implementation whereas our multi-core CPU algorithm achieves a speedup of 8 times over the single-threaded implementation. The CPU and GPU versions achieve near-identical registration quality in terms of RMS differences between the generated vector fields.

A 29-year-old male university student, with no prior history of trauma, presented with a 1 year history of clear fluid leaking intermittently from his left nostril. His past medical history included bilateral gynaecomastia since age 12, and recent low libido. β2-transferrin analysis of the nasal fluid confirmed a diagnosis of cerebrospinal fluid (CSF) rhinorrhoea. The serum prolactin was grossly elevated at 42 700 mU/l and brain magnetic resonance imaging (MRI) revealed a large parasellar/sellar mass. A diagnosis of invasive macroprolactinoma complicated by spontaneous CSF rhinorrhoea was made. The patient was commenced on treatment with cabergoline, but while awaiting surgery to repair the CSF leak he developed streptococcus mitis and sanguis meningitis. He made an uncomplicated recovery with antibiotic treatment. Immediately following this episode, the CSF rhinorrhoea resolved spontaneously. Subsequently, a repeat MRI scan revealed dramatic involution of the pituitary mass and the serum prolactin had fallen to 604 mU/l.

A promising method of automating management tasks in computing systems is to formulate them as control or optimization problems in terms of performance metrics. For an online optimization scheme to be of practical value in a distributed setting, however, it must successfully tackle the curses of dimensionality and modeling. This paper develops a hierarchical control framework to solve performance management problems in distributed computing systems operating in a data center. Concepts from approximation theory are used to reduce the computational burden of controlling such large-scale systems. The relevant approximations are made in the construction of the dynamical models to predict system behavior and in the solution of the associated control equations. Using a dynamic resource-provisioning problem as a case study, we show that a computing system managed by the proposed control framework with approximation models realizes profit gains that are, in the best case, within 1% of a controller using an explicit model of the system.

This paper shows how to significantly accelerate cone-beam CT reconstruction and 3D deformable image registration using the stream-processing model. We describe data-parallel designs for the Feldkamp, Davis and Kress (FDK) reconstruction algorithm, and the demons deformable registration algorithm, suitable for use on a commodity graphics processing unit. The streaming versions of these algorithms are implemented using the Brook programming environment and executed on an NVidia 8800 GPU. Performance results using CT data of a preserved swine lung indicate that the GPU-based implementations of the FDK and demons algorithms achieve a substantial speedup--up to 80 times for FDK and 70 times for demons when compared to an optimized reference implementation on a 2.8 GHz Intel processor. In addition, the accuracy of the GPU-based implementations was found to be excellent. Compared with CPU-based implementations, the RMS differences were less than 0.1 Hounsfield unit for reconstruction and less than 0.1 mm for deformable registration.

This paper presents an overview of a major, long-term program for tropospheric gas and aerosol research in the southeastern United States. Building on three existing ozone (O3)-focused research sites begun in mid-1992, the Southeastern Aerosol Research and Characterization Study (SEARCH) was initiated in mid-1998 as a 7-year observation and research program with a broader focus including aerosols and an expanded geographical coverage in the Southeast. The monitoring network comprises four urban-rural (or urban-suburban) site pairs at locations along the coast of the Gulf of Mexico and inland, including two moderately sized and two major urban areas (Pensacola, FL; Gulfport, MS; Atlanta, GA; and Birmingham, AL). The sites are equipped with an extensive suite of instruments for measuring particulate matter (PM), gases relevant to secondary O3 and the production of secondary aerosol particles, and surface meteorology. The measurements taken to date have added substantially to the knowledge about the temporal behavior and geographic variability of tropospheric aerosols in the Southeast. Details are presented in four papers to follow.

This paper reports the milk protein polymorphism, the allele frequencies of variants and the possible linkages among various combinations of milk protein phenotypes in the Kangayam cattle of south India. Milk samples from 156 Kangayam cows were typed by starch gel and polyacrylamide gel electrophoresis for caseins and whey proteins, respectively. All the four milk protein components studied, alpha(s)1-casein. beta-casein, beta-lactoglobulin and alpha-lactalbumin, exhibited polymorphism with high allele frequencies of 0.9231 +/- 0.0151 for alpha(s)1-casein C, 0.9263 +/- 0.0148 for beta-casein A, 0.9135 +/- 0.0159 for beta-lactoglobulin B and a relatively high frequency of 0.6218 +/- 0.0275 for alpha-lactalbumin A. The mean heterozygosity estimated over all the four milk protein loci was 0.2420. Genetic equilibrium was observed among all the loci studied, except alpha-lactalbumin. Linkage analysis confirmed the non-independence between alpha(s)1- and beta-caseins and between caseins and alpha-lactalbumin phenotypes.

The effect of stress on risk-taking or risk-averse behavior in decision-making has been inconclusive in previous research, with few studies revealing the underlying neural mechanisms. This study employed event-related potentials technique and combined a social cold pressor assessment test with a mental arithmetic task to induce stress responses, aiming to investigate the influence of exogenous stress on the risk decision-making process. Stress induction results indicated that, in addition to raising heart rate and blood pressure, stress responses were accompanied by enhanced negative emotions, diminished positive emotions, and alterations in neural activity. The outcomes of risk decision-making showed that stress did not significantly affect risk preference or time of choice but did reduce the feedback-related negativity/reward positivity, with a particularly significant effect observed for large outcomes. Stress also altered the amplitude of the P3 component, with stress decreasing the P3 value for winning outcomes relative to losing outcomes. The study suggests that understanding how stress affects risk preference should consider the emotional valence induced by stress. Contrary to the reward sensitivity hypothesis, stress weakened reward sensitivity. Stress led to changes in the allocation of cognitive resources for outcome evaluation: compared to negative outcomes, stress reduced cognitive resources for positive outcomes, which might be related to the enhanced negative emotions induced by stress. The study highlights the importance of focusing on the subjective emotional experience induced by stress in future research on stress and risk decision-making., (© 2024 Society for Psychophysiological Research.)

Previous studies have shown that people prefer risk-taking at the end of gambles, a phenomenon called the ending effect. By using the Guess Gambling Game, we investigated the impact of gain-loss status on the ending effect (Experiment 1) and whether and how this effect may be affected by time reference (Experiment 2) and gender (Experiment 1&2). In Experiment 1, we observed the ending effect only in the gain group. Furthermore, gender differences exist in the loss group behavior, females were more risk-averse than males, and males tend to investment more initially and then reduce their investment in a U-shaped pattern (Experiment 1&2). Next, in Experiment 2, the findings indicated that participants in the gain group made riskier decisions and were willing to allocate more money for additional decision opportunities, irrespective of the time conditions. Additionally, under time-limited condition, participants tended to make more decisions in the final round, aiming to maximize their choices times within the limited time. These results contribute to a better understanding of the boundary conditions surrounding the ending effect in risky decision-making and may offer a scientific basis for mitigating and intervening in irrational decision-making., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Emotions have been theorized to be important drivers of economic choices, such as intertemporal or risky decisions. Our systematic review and meta-analysis of the previous literature (378 results and 50,972 participants) indicates that the empirical basis for these claims is mixed and the cross-cultural generalizability of these claims has yet to be systematically tested. We analysed a dataset with representative samples from 74 countries (n = 77,242), providing a multinational test of theoretical claims that individuals' ongoing emotional states predict their economic preferences regarding time or risk. Overall, more positive self-reported emotions generally predicted a willingness to wait for delayed rewards or to take favourable risks, in line with some existing theories. Contrary to the assumption of a universal relationship between emotions and decision-making, we show that these relationships vary substantially and systematically across countries. Emotions were stronger predictors of economic decisions in more economically developed and individualistic countries., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To report our experience with 18 F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRI CR ) in the care trajectory for persistent acromegaly., Design: Prospective case series., Patients: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options., Measurements: FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery., Results: FET-PET/MRI CR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRI CR was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRI CR identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRI CR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients., Conclusions: In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRI CR is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

Horses revolutionized human history with fast mobility 1 . However, the timeline between their domestication and their widespread integration as a means of transport remains contentious 2-4 . Here we assemble a collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged around 2200 BCE, through close-kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than approximately 2700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe around 3000 BCE and earlier 3,5 . Finally, we detect significantly shortened generation times at Botai around 3500 BCE, a settlement from central Asia associated with corrals and a subsistence economy centred on horses 6,7 . This supports local horse husbandry before the rise of modern domestic bloodlines., (© 2024. The Author(s).)