McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues

Relationship between urinary calcium and calcium intake during calcitriol administration

Relationship between urinary calcium and calcium intake during calcitriol administration. The hypercalciuria that occurs when 1,25(OH)2D3 (calcitriol) is given to humans with normal renal function depends on dietary Ca absorption and may also relate, in part, to enhanced bone resorption. To evaluate the relationship between urinary and dietary Ca during treatment with calcitriol, 12 metabolic balance studies were performed in normal volunteers ingesting a diet containing 350 mg/day of Ca, to which Ca gluconate was added. After 10 days on either 350 mg/day or 1550 mg/day of Ca, calcitriol, 0.5 µg every 12hr, was given. Then diet Ca was changed in successive 5-day treatment periods from 350 to 650, 950 and 1550 mg/day (group A) or from 1550 to 950, 650 and 350 mg/day (group B). On the lowest diet Ca, urinary Ca was less than Ca intake during calcitriol treatment (group A, 220 ± 50 mg/day; group B, 247 ± 40). As diet Ca was changed during calcitriol treatment, urinary Ca correlated with diet Ca (r = 0.60) until diet Ca reached 950 mg/day. With calcitriol, serum iPTH fell by 18 to 25% (P < 0.01) and urinary hydroxyproline fell by 11 to 19% (P < 0.05 to 0.01). Baseline serum levels of 1,25(OH)2D were 47 ± 8 and 34 ± 5 pg/ml in group A and B, respectively, and the values increased to 51 ± 12 and 45 ±7.4 pg/ml during treatment with calcitriol. Serum Ca from fasted subjects was not affected by calcitriol, but the mean postabsorptive serum Ca (noon) was increased by 0.35 mg/dl. Although urine Ca/creatinine from fasted subjects increased with calcitriol treatment, the values varied directly with the 24-hr urine Ca and inversely with serum iPTH levels. Thus, dietary Ca is the major determinant of urinary Ca during treatment with calcitriol, and the latter may decrease dietary Ca requirements. There was no evidence for an increased bone resorption. The reduction of hydroxyproline excretion suggests that bone resorption was initially depressed, perhaps due to iPTH suppression. The data also suggest that urine Ca/creatinine after fasting for 12 hr is influenced by previous dietary Ca intake or intestinal Ca absorption, perhaps related to changing iPTH levels

Discussions and Reviews : Theorizing about theory in international politics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66906/2/10.1177_002200276000400405.pd

Machine learning for the Zwicky transient facility

The Zwicky Transient Facility is a large optical survey in multiple filters producing hundreds of thousands of transient alerts per night. We describe here various machine learning (ML) implementations and plans to make the maximal use of the large data set by taking advantage of the temporal nature of the data, and further combining it with other data sets. We start with the initial steps of separating bogus candidates from real ones, separating stars and galaxies, and go on to the classification of real objects into various classes. Besides the usual methods (e.g., based on features extracted from light curves) we also describe early plans for alternate methods including the use of domain adaptation, and deep learning. In a similar fashion we describe efforts to detect fast moving asteroids. We also describe the use of the Zooniverse platform for helping with classifications through the creation of training samples, and active learning. Finally we mention the synergistic aspects of ZTF and LSST from the ML perspective

Machine learning for the Zwicky Transient Facility

The Zwicky Transient Facility is a large optical survey in multiple filters producing hundreds of thousands of transient alerts per night. We describe here various machine learning (ML) implementations and plans to make the maximal use of the large data set by taking advantage of the temporal nature of the data, and further combining it with other data sets. We start with the initial steps of separating bogus candidates from real ones, separating stars and galaxies, and go on to the classification of real objects into various classes. Besides the usual methods (e.g., based on features extracted from light curves) we also describe early plans for alternate methods including the use of domain adaptation, and deep learning. In a similar fashion we describe efforts to detect fast moving asteroids. We also describe the use of the Zooniverse platform for helping with classifications through the creation of training samples, and active learning. Finally we mention the synergistic aspects of ZTF and LSST from the ML perspective

Evidence of the Importance of Host Habitat Use in Predicting the Dilution Effect of Wild Boar for Deer Exposure to Anaplasma spp

Foci of tick-borne pathogens occur at fine spatial scales, and depend upon a complex arrangement of factors involving climate, host abundance and landscape composition. It has been proposed that the presence of hosts that support tick feeding but not pathogen multiplication may dilute the transmission of the pathogen. However, models need to consider the spatial component to adequately explain how hosts, ticks and pathogens are distributed into the landscape

Can Sophie's Choice Be Adequately Captured by Cold Computation of Minimizing Losses? An fMRI Study of Vital Loss Decisions

The vast majority of decision-making research is performed under the assumption of the value maximizing principle. This principle implies that when making decisions, individuals try to optimize outcomes on the basis of cold mathematical equations. However, decisions are emotion-laden rather than cool and analytic when they tap into life-threatening considerations. Using functional magnetic resonance imaging (fMRI), this study investigated the neural mechanisms underlying vital loss decisions. Participants were asked to make a forced choice between two losses across three conditions: both losses are trivial (trivial-trivial), both losses are vital (vital-vital), or one loss is trivial and the other is vital (vital-trivial). Our results revealed that the amygdala was more active and correlated positively with self-reported negative emotion associated with choice during vital-vital loss decisions, when compared to trivial-trivial loss decisions. The rostral anterior cingulate cortex was also more active and correlated positively with self-reported difficulty of choice during vital-vital loss decisions. Compared to the activity observed during trivial-trivial loss decisions, the orbitofrontal cortex and ventral striatum were more active and correlated positively with self-reported positive emotion of choice during vital-trivial loss decisions. Our findings suggest that vital loss decisions involve emotions and cannot be adequately captured by cold computation of minimizing losses. This research will shed light on how people make vital loss decisions

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington\u27s Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington\u27s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington\u27s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression