Positron detection in silica monoliths for miniaturised quality control of PET radiotracers

We demonstrate the use of the miniaturised Medipix positron sensor for detection of the clinical PET radiotracer, [⁶⁸Ga]gallium-citrate, on a silica-based monolith, towards microfluidic quality control. The system achieved a far superior signal-to-noise ratio compared to conventional sodium iodide-based radio-HPLC detection and allowed real-time visualisation of positrons in the monolith

Alcohol Discrimination and Preferences in Two Species of Nectar-Feeding Primate

Recent reports suggest that dietary ethanol, or alcohol, is a supplemental source of calories for some primates. For example, slow lorises (Nycticebus coucang) consume fermented nectars with a mean alcohol concentration of 0.6% (range: 0.0–3.8%). A similar behaviour is hypothesized for aye-ayes (Daubentonia madagascariensis) based on a single point mutation (A294V) in the gene that encodes alcohol dehydrogenase class IV (ADH4), the first enzyme to catabolize alcohol during digestion. The mutation increases catalytic efficiency 40-fold and may confer a selective advantage to aye-ayes that consume the nectar of Ravenala madagascariensis. It is uncertain, however, whether alcohol exists in this nectar or whether alcohol is preferred or merely tolerated by nectarivorous primates. Here, we report the results of a multiple-choice food preference experiment with two aye-ayes and a slow loris. We conducted observer-blind trials with randomized, serial dilutions of ethanol (0–5%) in a standard array of nectar- simulating sucrose solutions. We found that both species can discriminate varying concentrations of alcohol; and further, that both species prefer the highest available concentrations. These results bolster the hypothesized adaptive function of the A294V mutation in ADH4, and a connection with fermented foods, both in aye-ayes and the last common ancestor of African apes and humans

A standardized comparison of peri-operative complications after minimally invasive esophagectomy: Ivor Lewis versus McKeown.

BACKGROUND: While our institutional approach to esophageal resection for cancer has traditionally favored a minimally invasive (MI) 3-hole, McKeown esophagectomy (MIE 3-hole) during the last five years several factors has determined a shift in our practice with an increasing number of minimally invasive Ivor Lewis (MIE IL) resections being performed. We compared peri-operative outcomes of the two procedures, hypothesizing that MIE IL would be less morbid in the peri-operative setting compared to MIE 3-hole. METHODS: Our institution\u27s IRB-approved esophageal database was queried to identify all patients who underwent totally MI esophagectomy (MIE IL vs. MIE 3-hole) from June 2011 to May 2016. Patient demographics, preoperative and peri-operative data, as well as post-operative complications were compared between the two groups. Post-operative complications were analyzed using the Clavien-Dindo classification system. RESULTS: There were 110 patients who underwent totally MI esophagectomy (MIE IL n = 49 [45%], MIE 3-hole n = 61 [55%]). The majority of patients were men (n = 91, 83%) with a median age of 62.5 (range 31-83). Preoperative risk stratifiers such as ECOG score, ASA, and Charlson Comorbidity Index were not significantly different between groups. Anastomotic leak rate was 2.0% in the MIE IL group compared to 6.6% in the MIE 3-hole group (p = 0.379). The rate of serious (Clavien-Dindo 3, 4, or 5) post-operative complications was significantly less in the MIE IL group (34.7 vs. 59.0%, p = 0.013). Serious pulmonary complications were not significantly different (16.3 vs. 26.2%, p = 0.251) between the two groups. CONCLUSIONS: In this cohort, totally MIE IL showed significantly less severe peri-operative morbidity than MIE 3-hole, but similar rates of serious pulmonary complications and anastomotic leaks. These findings confirm the safety of minimally invasive Ivor Lewis esophagectomies for esophageal cancer when oncologically and clinically appropriate. Minimally invasive McKeown esophagectomy remains a satisfactory and appropriate option when clinically indicated

Marginal Cost Analysis of Two Train-the-Trainer Models for Implementing SafeCare

[West J Emerg Med. 2014;15(5):623–626.

Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause defects in hematopoiesis and in thymocyte apoptosis

The proapoptotic members of the Bcl-2 family can be subdivided into members that contain several Bcl-2 homology (BH) domains and those that contain only the BH3 domain. Although it is known that BH3-only proteins and the multi-BH domain proteins, Bak and Bax, are essential for programmed cell death, the overlapping role of these two subgroups has not been examined in vivo. To investigate this, we generated Bak/Bim and Bax/Bim double deficient mice. We found that although Bax−/−Bim−/−, but not Bak−/−Bim−/−, mice display webbed hind and front paws and malocclusion of the incisors, both groups of mice present with dysregulated hematopoiesis. Combined loss of Bak and Bim or Bax and Bim causes defects in myeloid and B-lymphoid development that are more severe than those found in the single knock-out mice. Bak−/−Bim−/− mice have a complement of thymocytes that resembles those in control mice, whereas Bax−/−Bim−/− mice are more similar to Bim−/− mice. However, thymocytes isolated from Bak−/−Bim−/− or Bax−/−Bim−/− mice are markedly more resistant to apoptotic stimuli mediated by the intrinsic pathway as compared with thymocytes from single-knockout mice. These data suggest an essential overlapping role for Bak or Bax and Bim in the intrinsic apoptotic pathway

Optical control of ground-state atomic orbital alignment: Cl(P-2(3/2)) atoms from HCl(v=2,J=1) photodissociation

H(35)Cl(v=0,J=0) molecules in a supersonic expansion were excited to the H(35)Cl(v=2,J=1,M=0) state with linearly polarized laser pulses at about 1.7 microm. These rotationally aligned J=1 molecules were then selectively photodissociated with a linearly polarized laser pulse at 220 nm after a time delay, and the velocity-dependent alignment of the (35)Cl((2)P(32)) photofragments was measured using 2+1 REMPI and time-of-flight mass spectrometry. The (35)Cl((2)P(32)) atoms are aligned by two mechanisms: (1) the time-dependent transfer of rotational polarization of the H(35)Cl(v=2,J=1,M=0) molecule to the (35)Cl((2)P(32)) nuclear spin which is conserved during the photodissociation and thus contributes to the total (35)Cl((2)P(32)) photofragment atomic polarization] and (2) the alignment of the (35)Cl((2)P(32)) electronic polarization resulting from the photoexcitation and dissociation process. The total alignment of the (35)Cl((2)P(32)) photofragments from these two mechanisms was found to vary as a function of time delay between the excitation and the photolysis laser pulses, in agreement with theoretical predictions. We show that the alignment of the ground-state (35)Cl((2)P(32)) atoms, with respect to the photodissociation recoil direction, can be controlled optically. Potential applications include the study of alignment-dependent collision effects

Exercise Training Improves Cardiac and Skeletal Muscle Metabolism in Rats with Pulmonary Arterial Hypertension

poster abstractIn patients with pulmonary arterial hypertension (PAH), a shift from oxidative to glycolytic metabolism promotes right ventricular (RV) and skeletal muscle dysfunction that contributes to reduced exercise tolerance. As seen for other cardiopulmonary diseases, exercise training (ExT) may ameliorate this glycolytic switch in PAH and improve exercise capacity. The purpose of this research is to investigate ExT in a rat model of PAH on markers of glycolytic and oxidative metabolism in RV and skeletal muscle. Male Sprague-Dawley rats received monocrotaline (MCT, 40 mg/kg, s.q.) to induce PAH (n= 13), or saline, for healthy controls (n=5). After 2 wks, with MCT-induced PAH established, 6 wks of treadmill (TM) ExT was initiated for a subset of PAH animals (PAH-ExT, n= 6) and healthy controls (CON-ExT, n=3). ExT runs progressed up to 60 min at mild relative intensity, 50% of maximal aerobic capacity (VO2max). VO2max was assessed at baseline, in pre-training and post-training TM testing via analysis of expired gases. Abundance of Glut-1, a marker of glycolytic metabolism, was evaluated in cryosections of RV and soleus with immunofluorescent (IF) staining and quantification. Data are presented as mean±SE. MCT-ExT rats maintained aerobic capacity over 6 wks better than sedentary counterparts (MCT-SED)(VO2max= -134±109 vs. -521±129 ml/kg/hr, p=0.04) and was not different than CON-ExT (-201±31 ml/kg/hr, p=0.82). A lower abundance of Glut-1 was observed in both RV and soleus myocytes of PAH-ExT rats (MPI= 10.9 ±0.9 for RV; 13.7±0.8 for soleus) compared to PAH-SED rats (15.7±2.4, p=0.05, for RV; 17.4±1.4, p=0.04, for soleus) and was similar to CON-ExT rats (13.0±2.2, p=0.33, for RV; 9.0±2.3, p=0.26, for soleus), indicative of a shift toward greater dependency on oxidative metabolism. Exercise training attenuates functional decline following MCT administration in rats. Preservation of aerobic capacity may be explained by promotion of more efficient RV and skeletal muscle mitochondrial substrate utilization

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria

The endowment effect and beliefs about the market

The endowment effect occurs when people assign a higher value to an item they own than to the same item when they do not own it, and this effect is often taken to reflect an ownership-induced change in the intrinsic value people assign to the object. However recent evidence shows that valuations made by buyers and sellers are influenced by market prices provided for the individual products, suggesting a role for beliefs about the markets. Here we elicit individuals’ beliefs about whole distributions of market prices, enabling us to quantify whether or not a given transaction constitutes a “good deal” and to demonstrate how an endowment effect may reflect such considerations. In a meta-analysis and three laboratory experiments, we show for the first time that ownership has no effect on beliefs about either: (a) the quality of the item or (b) the appropriate market price for the item. Instead, we show that sellers demand a price for the item that matches their beliefs about the item’s relative quality and the distribution of market prices in the market. Buyers, in contrast, offer less than what they believe the appropriate market price is. Thus, we argue that the endowment effect may largely reflect “adaptively rational” behavior on the part of both buyers and sellers (given their beliefs about relevant markets) rather than any ownership-induced bias or change in intrinsic preferences