The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

The current orthodoxy is that home is the best and preferred place of death for most people, but in this podcast, Kristian Pollock a sociologist from Nottingham University questions these assumptions and calls for greater attention to improving the experience of dying in hospital and elsewhere. Read the full...

15s30m is a social movement to reduce frustration & increase joy - the idea is to spend 15 seconds of your time now, and save someone else 30 minutes down the line. To talk about their movement we're joined by the founders, Rachel Pilling, consultant ophthalmologist, and Dan Wadsworth, transformation manager - both from Bradford Teaching...

Ted Kaptchuk, professor of medicine at Harvard Medical school - and leading placebo researcher, has just published an analysis on bmj.com describing the effect of open label placebo - placebos that patient's know are placebos, but still seem to have some clinical effect. Ted joins us to speculate about what's going on in the body, what this means...

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10^–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.

5 November 2019

This ethnographic study is the first of its kind to analyse energy access and resilience strategies deployed in two refugee camps in Kenya and Burkina Faso. It highlights the need for new methodological approaches to expand the evidence base for humanitarian energy interventions and policies.

Nearly 6 million Afghans fled after violence erupted in the late 1970s, primarily to Iran and Pakistan. While millions returned after the collapse of the Taliban in 2001, the security situation has since deteriorated and the government struggles to meet the needs of vulnerable populations, particularly the internally displaced. This country profile explores Afghanistan’s complex migration and displacement history as well as ongoing challenges.

With nearly 1.4 million internally displaced persons (IDPs), Ukraine is home to one of the largest IDP populations in the world. Five years after Russia's annexation of Crimea, displaced Ukrainians continue to face challenges related to national identity, social cohesion, and political participation. While the Ukrainian government has had some success integrating IDPs, the conflict’s end remains uncertain, and many are unlikely to return to their communities of origin no matter the outcome.

From earthquakes to drought, natural disasters and climate change played a key role in migration flows in 2015. Climate-induced migration surfaced as a concern at the United Nations Climate Change Conference (known as COP21) as international organizations and policymakers have begun to recognize the growing challenges, and potential protection obligations, of such movement.

Climate-related displacement is not hypothetical: An average of 21.5 million people per year have been displaced since 2008 by natural disasters, and thousands more have fled slow-onset environmental hazards. While migration can serve as a safety valve to adapt to changing conditions, few orderly, legal channels exist for climate migrants (also known as environmental migrants), as this article explores.

OBJECTIVE

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

OBJECTIVE

Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.

Robert R. Henry
Mar 1, 2015; 38:412-419
Evolving Tactics With Inhibition of Sodium-Glucose Cotransporters

Hans-Ulrich Häring
Jun 1, 2014; 37:1650-1659
Emerging Technologies and Therapeutics

Khalid A. Jadoon
Oct 1, 2016; 39:1777-1786
Emerging Technologies and Therapeutics

Vanita R. Aroda
Sep 1, 2019; 42:1724-1732
Emerging Therapies: Drugs and Regimens

OBJECTIVE

Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone.

OBJECTIVE

To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI.

Shortly after the Sept. 11, 2001, attacks, psychologist Jennifer Lerner conducted a national field experiment: She asked a random sampling of Americans how likely it was that they would be the victim of a terrorist attack in the next 12 months.

In Eliot Spitzer's sex scandal and tragicomic downfall, the question that bugged many people did not have to do with ethics or politics, but whether Spitzer got a raw deal.

John B. Buse
Jul 1, 2002; 20:
Feature Articles

State Board of Education members weighed in today about a proposal to eliminate their elected positions and replace the board with an appointed commission.

An internationally known gifted-education center is scouting—and helping to develop—gifted students in after-school programs and pullout classes in one of Maryland’s most challenged school districts.

Gov. Christie has pushed to flatten the state's funding formula so that the state's impoverished urban districts would get the same amount of money wealthy suburban districts get.

The Knowledge Sharing for the Development of Learning Resources tutorial provides a professional step forward, a learning experience that leads to recognition that your leadership is well founded as well as ensuring that participants in the development of learning resources recognize they are contributing to an exceptional achievement.

Guantánamo Bay Detention Camp.

Paris : G. Steinheil, 1892.

[Edinburgh] : [publisher not identified], [1890]

In a case implicating the use of schools as voting locations as well as free speech in education, the justices said Minnesota went too far.

[London] (Haymarket) : Published ... for the proprietors, by T McLean, Septr. 1. 1836 ([London?] : Printed by Lahee & Co.)

The NHL suspended its season March 12 with 189 regular-season games left.

Stuttgart : Franz Steiner Verlag, 2019.

Over four years in Eugene, Ruthy Hebard has made a name for herself with reliability and dynamic play. She's had many memorable moments in a Duck uniform. But her career day against Washington State (34 points), her moment reaching 2,000 career points and her NCAA record for consecutive made FGs (2018) tops the list. Against the Trojans, she set the record (30) and later extended it to 33.

We develop ancestral Gumbel-Top-$k$ sampling: a generic and efficient method for sampling without replacement from discrete-valued Bayesian networks, which includes multivariate discrete distributions, Markov chains and sequence models. The method uses an extension of the Gumbel-Max trick to sample without replacement by finding the top $k$ of perturbed log-probabilities among all possible configurations of a Bayesian network. Despite the exponentially large domain, the algorithm has a complexity linear in the number of variables and sample size $k$. Our algorithm allows to set the number of parallel processors $m$, to trade off the number of iterations versus the total cost (iterations times $m$) of running the algorithm. For $m = 1$ the algorithm has minimum total cost, whereas for $m = k$ the number of iterations is minimized, and the resulting algorithm is known as Stochastic Beam Search. We provide extensions of the algorithm and discuss a number of related algorithms. We analyze the properties of ancestral Gumbel-Top-$k$ sampling and compare against alternatives on randomly generated Bayesian networks with different levels of connectivity. In the context of (deep) sequence models, we show its use as a method to generate diverse but high-quality translations and statistical estimates of translation quality and entropy.

Bastien Mallein.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 2, 356--373.

Abstract:
Consider a supercritical branching random walk on the real line. The consistent maximal displacement is the smallest of the distances between the trajectories followed by individuals at the $n$th generation and the boundary of the process. Fang and Zeitouni, and Faraud, Hu and Shi proved that under some integrability conditions, the consistent maximal displacement grows almost surely at rate $lambda^{*}n^{1/3}$ for some explicit constant $lambda^{*}$. We obtain here a necessary and sufficient condition for this asymptotic behaviour to hold.

[London?], [199-?]

Fabrizio Benedetti
Nov 9, 2005; 25:10390-10402
Symposia and Mini-Symposia

Geoscientists noticed the normal rumbles of human activity picked up by their instruments have died down as much of the world ground to a halt

The new book 'The Rainbow Atlas' invites readers on a vivid journey across the globe

Why not use quarantine as an opportunity to have your homeschoolers master woodworking or engine repair?

The National Trust for Historic Preservation is looking for 1,000 places tied to women's history, and to share the stories of the figures behind them

The remote cabin could be the difference between life and death for travellers stuck on the territory’s long winter road. It was built to remember Stella Barnaby, who would have been 55 this Saturday.

Seven people were displaced by a fire early Saturday on the north end of Saint John.

Leonard Rodriquez's grieving loved ones say he was a man who would drop everything to help those in need. But they say his death could have been prevented if he'd had the personal protective gear he needed to do his job.