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Hypoparathyroidism (HypoPT) is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. HypoPT is most commonly seen after neck surgery, which accounts for approximately 75% of cases, whereas approximately 25% have HypoPT due to nonsurgical causes. In both groups of patients, conventional therapy includes calcium and active vitamin D analogue therapy aiming to maintain serum calcium concentration in the low normal or just below the normal reference range and normalize serum phosphorus, magnesium concentrations, and urine calcium levels. The limitations of conventional therapy include wide fluctuations in serum calcium, high pill burden, poor quality of life, and renal complications. Parathyroid hormone (PTH) replacement therapy may improve the biochemical profile in those in whom conventional therapy proves unsatisfactory. Based on a systematic review and meta-analysis of the literature, the panel made a graded recommendation suggesting conventional therapy as first line therapy rather than administration of PTH (weak recommendation, low quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers use of PTH. Because pregnancy and lactation are associated with changes in calcium homeostasis close monitoring is required during these periods, with appropriate adjustment of calcium and active vitamin D analogue therapy to ensure that serum calcium remains in the mid to low normal reference range in order to avoid maternal and fetal complications. Emerging therapies include molecules with prolonged PTH action as well as different mechanisms of action that may significantly enhance drug efficacy and safety. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Methylation profiling has radically transformed our understanding of tumors previously called central nervous system primitive neuro-ectodermal tumors (CNS-PNET). While this marks a momentous step toward defining key differences, reclassification has thrown treatment into disarray. To shed light on response to therapy and guide clinical decision-making, we report outcomes and molecular features of children with CNS-PNETs from two multi-center risk-adapted studies (SJMB03 for patients ≥ 3 years; SJYC07 for patients 3 years) complemented by a non-protocol institutional cohort. Seventy patients who had a histological diagnosis of CNS-PNET or CNS embryonal tumor from one of the new categories that has supplanted CNS-PNET were included. This cohort was molecularly characterized by DNA methylation profiling (n = 70), whole-exome sequencing (n = 53), RNA sequencing (n = 20), and germline sequencing (n = 28). Clinical characteristics were detailed, and treatment was divided into craniospinal irradiation (CSI)-containing (SJMB03 and SJMB03-like) and CSI-sparing therapy (SJYC07 and SJYC07-like). When the cohort was analyzed in its entirety, no differences were observed in the 5-year survival rates even when CSI-containing therapy was compared to CSI-sparing therapy. However, when analyzed by DNA methylation molecular grouping, significant survival differences were observed, and treatment particulars provided suggestions of therapeutic response. Patients with CNS neuroblastoma with FOXR2 activation (CNS-NB-FOXR2) had a 5-year event-free survival (EFS)/overall survival (OS) of 66.7% ± 19.2%/83.3% ± 15.2%, and CIC rearranged sarcoma (CNS-SARC-CIC) had a 5-year EFS/OS both of 57.1% ± 18.7% with most receiving regimens that contained radiation (focal or CSI) and multidrug chemotherapy. Patients with high-grade neuroepithelial tumor with BCOR alteration (HGNET-BCOR) had abysmal responses to upfront chemotherapy-only regimens (5-year EFS = 0%), but survival extended with salvage radiation after progression [5-year OS = 53.6% ± 20.1%]. Patients with embryonal tumor with multilayered rosettes (ETMR) or high-grade glioma/glioblastoma multiforme (HGG/GBM) did not respond favorably to any modality (5-year EFS/OS = 10.7 ± 5.8%/17.9 ± 7.2%, and 10% ± 9.0%/10% ± 9.0%, respectively). As an accompaniment, we have assembled this data onto an interactive website to allow users to probe and query the cases. By reporting on a carefully matched clinical and molecular cohort, we provide the needed insight for future clinical management.

I consider a sample of eight pressure-supported low-surface brightness galaxies in terms of Milgrom's modified Newtonian dynamics (MOND). These objects include seven nearby dwarf spheroidal galaxies -- Sextans, Carina, Leo II, Sculptor, Draco, Leo I, Fornax, and the ultra-diffuse galaxy DF44. The objects are modelled as Milgromian isotropic isothermal spheres characterised by two parameters that are constrained by observations: the constant line-of-sight velocity dispersion and the central surface density. The velocity dispersion determines the total mass, and, with the implied mass-to-light ratio, the central surface brightness. This then specifies the radial run of surface brightness over the entire isothermal sphere. For these objects the predicted radial distribution of surface brightness is shown to be entirely consistent with observations. This constitutes a success for MOND that is independent of the reduced dynamical mass., Comment: 7 pages, 4 figures, minor errors in Table 1 corrected

Consciousness requires subjective experience in the 'now.' Establishing 'now' however necessitates temporal processing. In the current article, we review one method of altering consciousness, anaesthetic drug administration, and its effects on perceived duration.We searched PubMed, PsycInfo and ScienceDirect databases, and article reference sections, for combinations of anaesthetic drugs and time perception tasks, finding a total of 36 articles which met our inclusion criteria. We categorised these articles with regards to whether they altered the felt passage of time, short or long interval timing, or were motor timing tasks.We found that various drugs alter the perceived passage of time; ketamine makes time subjectively slow down while GABA-ergic drugs make time subjectively speed up. At short interval there is little established evidence of a shift in time perception, though temporal estimates appear more variable. Similarly, when asked to use time to optimize responses (i.e. in motor timing tasks), various anaesthetic agents make timing more variable. Longer durations are estimated as lasting longer than their objective duration, though there is some variation across articles in this regard.We conclude by proposing further experiments to examine time perception under altered states of consciousness and ask whether it is possible to perceive the passage of time of events which do not necessarily reach the level of conscious perception. The variety of methods used raises the need for more systematic investigations of time perception under anaesthesia. We encourage future investigations into the overlap of consciousness and time perception to advance both fields.

The authors reflect on their experiences hosting a literary contest for Spanish as a heritage language (SHL) at a major university in the Pacific Northwest. The contest is described and recommendations are offered for those seeking to host such a competition. The goal of this paper is to underscore the potential of SHL creative writing competitions to empower students and their communities, to foster student retention and success, and to promote SHL program growth.

This paper argues that the local dimension of working-class radicalism has been underestimated in accounts of the campaigns and agitations that fed into early Chartism. It illustrates this by exami...

The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported.To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia.Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505).46 U.S. and Canadian hospitals.Patients aged 50 years or older undergoing hip fracture surgery.Spinal or general anesthesia.Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care.A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups.Missing outcome data and multiple outcomes assessed.Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia.Patient-Centered Outcomes Research Institute

The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) surgical risk calculator (SRC) is an open access calculator predicting patients' risk of postoperative complications. This study aims to assess the validity of the SRC in patients undergoing microsurgical free flap reconstruction at an Australian tertiary referral centre.This is a retrospective cohort study of 200 consecutive patients treated up to November 2020. SRC-predicted rates of postoperative complications and hospital length of stay (LOS) were compared to those observed for the ablative and reconstructive components of the procedure. The performance of the SRC was assessed using Brier scores, area under the receiver operating characteristic (ROC) curve (AUC), and the Hosmer-Lemeshow test.For both ablative and reconstructive components, the SRC discriminates well for pneumonia and urinary tract infection, and it is calibrated well for readmission and sepsis, but it does not discriminate and calibrate well for any single outcome. SRC-predicted hospital LOS and actual LOS did not correlate well for the reconstructive component, but they correlated strongly for the ablative component.The SRC is a poor predictor of postoperative complication rates and hospital LOS in patients undergoing head and neck microsurgical reconstruction.

Background Perioperative arterial blood pressure management is a physiologically complex challenge influenced by multiple factors. Methods A multidisciplinary, international working subgroup of the Third Perioperative Quality Initiative (POQI) consensus meeting reviewed the (patho)physiology and measurement of arterial pressure as applied to perioperative medicine. We addressed predefined questions by undertaking a modified Delphi analysis, in which primary clinical research and review articles were identified using MEDLINE. Strength of recommendations, where applicable, were graded by National Institute for Health and Care Excellence (NICE) guidelines. Results Multiple physiological factors contribute to the perioperative physiological importance of arterial pressure: (i) arterial pressure is the input pressure to organ blood flow, but is not the sole determinant of perfusion pressure; (ii) blood flow is often independent of changes in perfusion pressure because of autoregulatory changes in vascular resistance; (iii) microvascular dysfunction uncouples microvascular blood flow from arterial pressure (haemodynamic incoherence). From a practical clinical perspective, we identified that: (i) ambulatory measurement is the optimal method to establish baseline arterial pressure; (ii) automated and invasive arterial pressure measurements have inherent physiological and technical limitations; (iii) individualised arterial pressure targets may change over time, especially in the perioperative period. There remains a need for research in non-invasive, continuous arterial pressure measurements, macro- and micro-circulatory control, regional perfusion pressure measurement, and the development of sensitive, specific, and continuous measures of cellular function to evaluate blood pressure management in a physiologically coherent manner. Conclusion The multivariable, complex physiology contributing to dynamic changes in perioperative arterial pressure may be underappreciated clinically. The frequently unrecognised dissociation between arterial pressure, organ blood flow, and microvascular and cellular function requires further research to develop a more refined, contextualised clinical approach to this routine perioperative measurement.

I consider the observed rotation curves of 12 gas-dominated low-surface-brightness galaxies -- objects in which the mass of gas ranges between 2.2 and 27 times the mass of the stellar disk (mean=9.4). This means that, in the usual decomposition of rotation curves into those resulting from various mass components, the mass-to-light ratio of the luminous stellar disk effectively vanishes as an additional adjustable parameter. It is seen that the observed rotation curves reflect the observed structure in gas surface density distribution often in detail. This fact is difficult to comprehend in the context of the dark matter paradigm where the dark halo completely dominates the gravitational potential in the low surface density systems; however it is expected result in the context of modified Newtonian dynamics (MOND) in which the baryonic matter is the only component. With MOND the calculated rotation curves are effectively parameter-free predictions., Comment: 9 pages, 4 figures, submitted

Background A multidisciplinary international working subgroup of the third Perioperative Quality Initiative consensus meeting appraised the evidence on the influence of preoperative arterial blood pressure and community cardiovascular medications on perioperative risk. Methods A modified Delphi technique was used, evaluating papers published in MEDLINE on associations between preoperative numerical arterial pressure values or cardiovascular medications and perioperative outcomes. The strength of the recommendations was graded by National Institute for Health and Care Excellence guidelines. Results Significant heterogeneity in study design, including arterial pressure measures and perioperative outcomes, hampered the comparison of studies. Nonetheless, consensus recommendations were that (i) preoperative arterial pressure measures may be used to define targets for perioperative management; (ii) elective surgery should not be cancelled based solely upon a preoperative arterial pressure value; (iii) there is insufficient evidence to support lowering arterial pressure in the immediate preoperative period to minimise perioperative risk; and (iv) there is insufficient evidence that any one measure of arterial pressure (systolic, diastolic, mean, or pulse) is better than any other for risk prediction of adverse perioperative events. Conclusions Future research should define which preoperative arterial pressure values best correlate with adverse outcomes, and whether modifying arterial pressure in the preoperative setting will change the perioperative morbidity or mortality. Additional research should define optimum strategies for continuation or discontinuation of preoperative cardiovascular medications.

Pulmonary fluid shifts can occur while scuba diving. Such shifts, generally thought to be rare, may result in a life-threatening phenomenon known as immersion pulmonary edema (IPE). This study aims to better classify the normal physiology of diving using ultrasound (US) to determine if these fluid shifts occur routinely during commercial diving work at the NASA Neutral Buoyancy Laboratory (NBL).Chest US was performed on commercial divers prospectively pre- and post-dive to evaluate the presence of B-lines in a total of 12 intercostal points on the anterior, posterior, and lateral chest wall. The number of B-lines at each anatomic site was recorded and scored by two independent reviewers. An increase in the number of B-lines post-dive was considered a positive result.There were 67 exposures; 39 (58%) had an increase of one or more B-lines post dive; 64% of the female exposures and 57% of the male exposures were positive for B-lines post-dive, suggesting no difference across gender (Fisher's exact; p = 0.763). After the dive, all divers remained asymptomatic.From our results, fluid shifts can be viewed as a normal, transient, and physiologic process in commercial divers. This correlation can be compared to the formation of low-grade venous gas emboli (VGE) from decompression that does not result in decompression sickness. Further study of US B-lines in symptomatic divers may define the utility of field US in the diagnosis and management of IPE, and help identify associated risk factors.

In this paper I describe numerical calculations of the motion of particles in a disk about a solar-mass object perturbed by a planet on a circular orbit with mass greater than 0.001 of the stellar mass. A simple algorithm for simulating bulk viscosity is added to the ensemble of particles, and the response of the disk is followed for several planet orbital periods. A two-arm spiral structure forms near the inner resonance (2-1) and extends to the planetary orbit radius (corotation). In the same way for gaseous disks on a galactic scale perturbed by a weak rotating bar-like distortion, this is shown to be related to the appearance of two perpendicular families of periodic orbits near the resonance combined with dissipation which inhibits the crossing of streamlines. Spiral density enhancements result from the crowding of streamlines due to the gradual shift between families. The results, such as the dependence of pitch-angle on radius and the asymmetry of the spiral features, resemble those of sophisticated calculations that include more physical effects. The morphology of structure generated in this way clearly resembles that observed in objects with well-defined two-arm spirals, such as SAO 206462. This illustrates that the process of spiral formation via interaction with planets in such disks can be due to orbital motion in a perturbed Keplerian field combined with kinematic viscosity.}, 12 pages, 11 figures, detailed comparison with observed system added. Minor errors corrected. Section added on role of dissipation. Accepted A&A

Summary Engaging patients—defined broadly as individuals with lived experience of a given condition, family members, caregivers, and the organisations that represent them—as partners in research is a priority for policymakers, funders, and the public. Nonetheless, formal efforts to engage patients are absent from most studies, and models to support meaningful patient engagement in clinical anaesthesia research have not been previously described. Here, we review our experience in developing and implementing a multifaceted patient engagement strategy within the Regional Versus General Anesthesia for Promoting Independence After Hip Fracture (REGAIN) surgery trial, an ongoing randomised trial comparing spinal vs general anaesthesia for hip fracture surgery in 1600 older adults across 45 hospitals in the USA and Canada. This strategy engaged patients and their representatives at both the level of overall trial oversight and at the level of individual recruiting sites. Activities spanned a continuum ranging from events designed to elicit patients' input on key decisions to longitudinal collaborations that empowered patients to actively participate in decision-making related to trial design and management. Engagement activities were highly acceptable to participants and led to concrete changes in the design and conduct of the REGAIN trial. The REGAIN experience offers a model for future efforts to engage patients as partners in clinical anaesthesia research, and highlights potential opportunities for investigators to increase the relevance of anaesthesia studies by incorporating patient voices and perspectives into the research process.