We present measurements of a long-range smoke transport event recorded on 20-21 July 2011 over Halifax, Nova Scotia, Canada, during the Quantifying the impact of BOReal forest fires on Tropospheric ...oxidants over the Atlantic using Aircraft and Satellites (BORTAS-B) campaign. Ground-based Fourier transform spectrometers and photometers detected air masses associated with large wildland fires burning in eastern Manitoba and western Ontario. We investigate a plume with high trace gas amounts but low amounts of particles that preceded and overlapped at the Halifax site with a second plume with high trace gas loadings and significant amounts of particulate material. We show that the first plume experienced a meteorological scavenging event, but the second plume had not been similarly scavenged. This points to the necessity to account carefully for the plume history when considering long-range transport since simultaneous or near-simultaneous times of arrival are not necessarily indicative of either similar trajectories or meteorological history. We investigate the origin of the scavenged plume, and the possibility of an aerosol wet deposition event occurring in the plume ~ 24 h prior to the measurements over Halifax. The region of lofting and scavenging is only monitored on an intermittent basis by the present observing network, and thus we must consider many different pieces of evidence in an effort to understand the early dynamics of the plume. Through this discussion we also demonstrate the value of having many simultaneous remote-sensing measurements in order to understand the physical and chemical behaviour of biomass burning plumes.
Anopheles gambiae M and S swarming behaviour in areas of sympatry in Burkina Faso revealed segregation between the two species with the occurrence of few mixed swarms without any hybrids.
•Anopheles ...gambiae M and S forms swarming and mating systems were investigated in Burkina Faso in areas of sympatry.•Few mixed swarms and mating pairs of the two species were collected.•Despite mixed swarms and mating pairs occurred, no mixed insemination was found in females.
The swarming behaviour of natural populations of Anopheles gambiae and An. coluzzii (formerly known as An. gambiae S and M forms, respectively) were investigated through longitudinal surveys conducted between July 2006 and October 2009 in two rural areas of south-western Burkina Faso where these forms are sympatric. In both sites, the majority of swarms were recorded above visual markers localised among houses. In Soumousso, a wooded area of savannah, 108 pairs caught in copula from 205 swarms were sampled; in VK7, a rice growing area, 491 couples from 250 swarms were sampled. If segregated swarms were the norm in both sites, many visual markers were shared by the two forms of An. gambiae. Furthermore, mixed swarms were collected annually in frequencies varying from one site to another, though no mixed inseminations were recorded, corroborating the low hybrid rate previously reported in the field. The occurrence of inter-specific mate-recognition mechanisms, which allow individuals to avoid hybridisation, is discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
There is an epidemic in New Zealand of infectious bovine anaemia associated with Theileria orientalis Ikeda type, an obligate intracellular protozoan parasite. To establish whether T. orientalis ...Ikeda type infection adversely affects fertility of bulls used for natural mating, a randomised controlled experimental study was conducted. Ten of 17 2-year-old Friesian bulls that had not been previously infected with T. orientalis were infected with T. orientalis Ikeda type and then evaluations occurred during a 20-week period. There were semen and libido evaluations every 2 weeks, starting 4 weeks before the date of infection. In addition, there were blood collections, for haematocrit and infection intensity evaluations, rectal temperatures recorded, and bulls weighed three times weekly for 13 weeks after infection and then once weekly until completion of the study. Physical activity meters were also attached from Days 9–60 and 65–124 post-infection. The ten bulls were successfully infected with T. orientalis Ikeda type and this resulted in a decrease in HCT to about 0.25 by 70 days post-infection. There were no effects of infection on semen quality; however, during the acute phase of infection, when the infection intensity was rapidly increasing, the infected bulls took a longer time period for repeated mounting of females, and were less dominant in the herd social heiracrchy. In conclusion, although the transitory effects on libido could reduce conception rates, the overall effects of T. orientalis Ikeda type infection on bull fertility will probably be little.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
γ-Hydroxybutyric acid (GHB), a minor metabolite of the inhibitory neurotransmitter GABA, can accumulate to significant concentrations in the heritable disorder of GABA degradation, succinic ...semialdehyde dehydrogenase (SSADH) deficiency (SSADHD). Moreover, GHB may be employed in therapeutic settings (treatment of narcolepsy), as well as instances of illicit activity, including acquaintance sexual assault and the induction of euphoria. High-affinity binding sites for GHB in the brain have been identified, although the absolute identity of these receptors remains unclear. Pharmacological antagonism of GHB binding may have multiple instances of therapeutic relevance. The high affinity GHB receptor antagonist, NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid) has not been piloted in humans. To address the potential clinical utility of NCS-382, we have piloted initial studies of its toxicology in HepG2 and primary hepatocyte cells. At high dose (0.5mM), NCS-382 showed no capacity for inhibition of microsomal CYPs (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and minimal potential for activation of xenobiotic nuclear receptors. Additional cellular integrity and functional assays (viability, oxidative stress, apoptosis, ATP production) revealed little evidence for cytotoxicity, and a low degree of dysregulation of >370 genes actively engaged in the mediation of cellular toxicity. In vitro testing indicates a low probability of cellular toxicity associated with NCS-382.
•NCS-382 did not inhibit multiple human microsomal cytochrome P450s•NCS-382 did not significantly induce xenobiotic nuclear receptors•NCS-382 did not provide evidence of cell toxicity•NCS-382 did not dysregulate multiple genes implicated in toxicological processes•NCS-382 appears to have a good safety profile.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Aliment Pharmacol Ther 2011; 34: 1123–1132
Summary
Background Cirrhotic patients have an impaired health‐related quality of life (HRQOL), which is usually analysed using static paper‐pencil ...questionnaires. The Patient Reported Outcomes Measurement Information System (PROMIS) computerised adaptive testing (CAT) are flexible, freely available, noncopyrighted, HRQOL instruments with US‐based norms across 11 domains. CAT presents five to seven questions/domain depending on the patient’s response, from large validated question banks. This provides brevity and precision equivalent to the entire question bank.
Aim To evaluate PROMIS CAT tools against ‘legacy instruments’ for cirrhotics and their informal caregivers.
Methods A total of 200 subjects: 100 cirrhotics (70 men, 53% decompensated) and 100 caregivers were administered the PROMIS and legacy instruments Sickness Impact Profile (SIP), Beck depression/anxiety inventories, Pittsburgh Sleep‐Quality Index (PSQI) and Epworth Sleepiness scale (ESS) concurrently. Both legacy and PROMIS results for patients were compared with caregivers and US norms. These were also compared between compensated and decompensated patients. Preference for SIP or PROMIS was inquired of a selected group (n = 70, 50% patients). Test – retest reliability was assessed in another group of 20 patients.
Results Patients had significant impairment on all PROMIS domains apart from anger and anxiety compared with caregivers and US norms (P < 0.02 to <0.0001). Decompensated patients had significantly worse sleep, pain, social and physical function scores compared with compensated ones, similar to legacy instruments. There was a statistically significant correlation between PROMIS and their corresponding legacy instruments. The majority (71%) preferred PROMIS over SIP. PROMIS tools had significant test – retest reliability (ICC range 0.759–0.985) when administered 12 ± 6 days apart.
Conclusion PROMIS computerised adaptive testing tools had significant concurrent and discriminant validity, test – retest reliability and subject preference for assessing HRQOL in cirrhotic patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Self-assembled thermoresponsive polymers in aqueous solution have great potential as smart, switchable materials for use in biomedical applications. In recent years, attention has turned to the ...reversibility of these polymers' thermal transitions, which has led to debate over what factors influence discrepancies in the transition temperature when heating the system compared to the temperature obtained when cooling the system, known as the thermal hysteresis. Herein, we synthesize micelles with tunable aggregation numbers (
) whose cores contain poly(
-butyl acrylate-
,
-dimethylacrylamide) (p(
BA-
-DMA)) and four different thermoresponsive corona blocks, namely poly(
-isopropylacrylamide) (pNIPAM), poly(
,
-diethylacrylamide) (pDEAm), poly(diethylene glycol monomethyl ether methacrylate) (pDEGMA) and poly(oligo(ethylene glycol) monomethyl ether methacrylate) (pOEGMA). By studying their thermoresponsive behavior, we elucidate the effects of changing numerous important characteristics both in the thermoresponsive chain chemistry and architecture, and in the structure of their self-assemblies. Our findings demonstrate large deviations in the reversibility between the self-assemblies and the corresponding thermoresponsive homopolymers; specifically we find that micelles whose corona consist of polymers with a brush-like architecture (pDEGMA and pOEGMA) exhibit irreversible phase transitions at a critical chain density. These results lead to a deeper understanding of stimuli-responsive self-assemblies and demonstrate the potential of tunable
micelles for uncovering structure-property relationships in responsive polymer systems.
We hypothesized that blood levels of γ-aminobutyric acid (GABA) and γ-hydroxybutyric acid (GHB), biomarkers of succinic semialdehyde dehydrogenase deficiency (SSADHD), would correlate with age. GABA ...and GHB were quantified in plasma and red blood cells (RBCs) from 18 patients (age range 5–41 years; median 8). Both metabolites negatively correlated with age (
P
< 0.05). Plasma and RBC GHB declined with age, reaching a nadir and approximate steady state by 10 years. Declining plasma GABA achieved this approximate steady state at 30–40 years of age. These biomarker relationships may reflect further GABA- and GHB-ergic neurotransmission imbalances that correlate with the onset of adolescent/adulthood neuropsychiatric morbidity and epilepsy in SSADHD.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Sickle cell disease (SCD) occurs in 2.8 % of our Jamaican antenatal population with homozygous HbSS being most associated with adverse maternal and perinatal outcomes.
A retrospective comparative ...analysis of HbSS, HbSC and HbSβThal pregnancy outcomes at the University Hospital of the West Indies (UHWI) between January 2012 and December 2022 was conducted.
Of 120 patients (138 pregnancies), obesity occurred in 36 % (20/56) of the 'non-HbSS' group, i.e. HbSβThal (55 %, 5/9) and HbSC (32 %, 15/47) combined vs. 9.7 % of the HbSS (8/82). HbSS patients had more crises requiring transfusions, acute chest syndrome (ACS), maternal 'near-misses' (OR=10.7, 95 % 3.5-32.3; p<0.001), hospitalizations (OR 7.6, 95 % CI 3.4-16.9; p<0.001), low birth weight (LBW) neonates (OR 3.1, 1.1-8.9; p=0.037) and preterm birth (OR=2.6, 1.2-5.8; p=0.018) compared to HbSC and HbSβThal. Low dose aspirin was prescribed in 43 %. Logistic regression showed those NOT on aspirin (n=76) had more miscarriages (22 v. 2 %), were LESS likely to have a live birth (75 v. 95 % (0.2, 0.04-0.57, p=0.005)), but surprisingly had fewer painful crises (28 v. 46 % (0.5, 0.03-0.9, p=0.03)).
HbSS women had a 10-fold excess of maternal near-misses. Additional research may further clarify the effects of aspirin on pregnancy outcomes as related to SCD genotypes.
Detection of ovarian cancer (OC) circulating tumour cells (CTCs) is primarily based on targeting epithelial markers, thus failing to detect mesenchymal tumour cells. More importantly, the immune ...checkpoint inhibitor marker PD-L1 has not been demonstrated on CTCs from OC patients. An antibody staining protocol was developed and tested using SKOV-3 and OVCA432 OC cell lines. We targeted epithelial (cytokeratin (CK) and EpCAM), mesenchymal (vimentin), and OC-specific (PAX8) markers for detection of CTCs, and CD45/16 and CD31 were used for the exclusion of white blood and vascular endothelial cells, respectively. PD-L1 was used for CTC characterisation. CTCs were enriched using the Parsortix™ system from 16 OC patients. Results revealed the presence of CTCs in 10 (63%) cases. CTCs were heterogeneous, with 113/157 (72%) cells positive for CK/EpCAM (epithelial marker), 58/157 (37%) positive for vimentin (mesenchymal marker), and 17/157 (11%) for both (hybrid). PAX8 was only found in 11/157 (7%) CTCs. In addition, 62/157 (39%) CTCs were positive for PD-L1. Positivity for PD-L1 was significantly associated with the hybrid phenotype when compared with the epithelial (
= 0.007) and mesenchymal (
= 0.0009) expressing CTCs. Characterisation of CTC phenotypes in relation to clinical outcomes is needed to provide insight into the role that epithelial to mesenchymal plasticity plays in OC and its relationship with PD-L1.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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