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1.
Syst Rev ; 13(1): 154, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858798

ABSTRACT

BACKGROUND: Frailty reduction and reversal have been addressed successfully among older populations within community settings. However, these findings may not be applicable to residential care settings, largely due to the complex and multidimensional nature of the condition. Relatively, few attempts at frailty prevention exist in residential settings. This review aims to identify and describe best practice models of care for addressing frailty among older populations in residential care settings. This research also sets out to explore the impact of multidisciplinary health service delivery models on health outcomes such as mortality, hospitalisations, quality of life, falls and frailty. METHODS: A scoping review of the literature was conducted to address the project objectives. Reference lists of included studies, bibliographic databases and the grey literature were systematically searched for literature reporting multidisciplinary, multidimensional models of care for frailty. RESULTS: The scoping review found no interventions that met the inclusion criteria. Of the 704 articles screened, 664 were excluded as not relevant. Forty articles were fully assessed, and while no eligible studies were found, relevant data were extracted from 10 near-eligible studies that reported single disciplines or single dimensions rather than a model of care. The physical, nutritional, medicinal, social and cognitive aspects of the near eligible studies have been discussed as playing a key role in frailty reduction or prevention care models. CONCLUSION: This review has identified a paucity of interventions for addressing and reducing frailty in residential care settings. High-quality studies investigating novel models of care for addressing frailty in residential care facilities are required to address this knowledge gap. Similarly, there is a need to develop and validate appropriate screening and assessment tools for frailty in residential care populations. Health service providers and policy-makers should also increase their awareness of frailty as a dynamic and reversible condition. While age is a non-modifiable predictor of frailty, addressing modifiable factors through comprehensive care models may help manage and prevent the physical, social and financial impacts of frailty in the ageing population.


Subject(s)
Frail Elderly , Frailty , Humans , Frailty/prevention & control , Aged , Residential Facilities , Quality of Life , Homes for the Aged
2.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38517258

ABSTRACT

We present the development of a versatile apparatus for 6.2 eV laser-based time and angle-resolved photoemission spectroscopy with micrometer spatial resolution (time-resolved µ-ARPES). With a combination of tunable spatial resolution down to ∼11 µm, high energy resolution (∼11 meV), near-transform-limited temporal resolution (∼280 fs), and tunable 1.55 eV pump fluence up to 3 mJ/cm2, this time-resolved µ-ARPES system enables the measurement of ultrafast electron dynamics in exfoliated and inhomogeneous materials. We demonstrate the performance of our system by correlating the spectral broadening of the topological surface state of Bi2Se3 with the spatial dimension of the probe pulse, as well as resolving the spatial inhomogeneity contribution to the observed spectral broadening. Finally, after in situ exfoliation, we performed time-resolved µ-ARPES on a ∼30 µm flake of transition metal dichalcogenide WTe2, thus demonstrating the ability to access ultrafast electron dynamics with momentum resolution on micro-exfoliated materials.

3.
Ann R Coll Surg Engl ; 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38362753

ABSTRACT

INTRODUCTION: The utilisation of laparoscopic appendicectomy (LA) in children remains contentious despite the well-recognised advantages of laparoscopic surgery. The purpose of this study was to compare intraoperative and postoperative outcomes in LA and open appendicectomy (OA) when performed by adult general surgeons outside specialist paediatric practice in younger children. METHODS: A retrospective review of all patients under the age of 13 who underwent LA for suspected appendicitis over a two-year period was conducted. These were case-matched with an equivalent number of patients who underwent OA during the same period. Intraoperative and postoperative outcomes were compared. RESULTS: Fifty-one patients underwent LA during the study period. Patient demographics were statistically equivalent with the OA cohort. A statistically significant longer median operating time (58 vs 49min) was noted in the LA group, but intraoperative outcomes were otherwise comparable. LA, when compared with OA, was associated with a significant improvement in postoperative length of stay (2 vs 3 days, p < 0.001), postoperative complication rate (0% vs 6%, p = 0.01), negative appendicectomy rate (3.9% vs 17.6%, p < 0.001) and 30-day readmission rate (0% vs 5.9%, p = 0.03). No patients in the LA group required conversion to open surgery. CONCLUSION: LA can be safely delivered by adult general surgeons to younger paediatric populations outside the setting of paediatric specialist practice, with statistically significant improvements in postoperative outcomes noted when compared with OA. These findings are of importance in the current healthcare context where adult general surgeons continue to perform the majority of paediatric appendicectomies.

4.
Phys Rev Lett ; 128(20): 207201, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35657897

ABSTRACT

The Elliott-Yafet theory of spin relaxation in nonmagnetic metals predicts proportionality between spin and momentum relaxation times for scattering centers such as phonons. Here, we test this theory in Al nanowires over a very large thickness range (8.5-300 nm), finding that the Elliott-Yafet proportionality "constant" for phonon scattering in fact exhibits a large, unanticipated finite-size effect. Supported by analytical and numerical modeling, we explain this via strong phonon-induced spin relaxation at surfaces and interfaces, driven in particular by enhanced spin-orbit coupling.

5.
Sci Rep ; 12(1): 7786, 2022 May 11.
Article in English | MEDLINE | ID: mdl-35545648

ABSTRACT

We report on the electronic and magnetic properties of superconductor-ferromagnet heterostructures fabricated by electron beam evaporation on to unheated thermally oxidised Si substrates. Polycrystalline Nb thin films (5 to 50 nm thick) were shown to possess reliably high superconducting critical temperatures ([Formula: see text]), which correlate well with the residual resistivity ratio (RRR) of the film. These properties improved during ex-situ annealing, resulting in [Formula: see text] and [Formula: see text]RRR increases of up 2.2 K ([Formula: see text] 40% of the pre-annealed [Formula: see text]) and 0.8 ([Formula: see text] 60% of the pre-annealed RRR) respectively. Nb/Pt/Co/Pt heterostructures showed substantial perpendicular anisotropy in the ultrathin limit (≤ 2.5 nm), even in the extreme limit of Pt(0.8 nm)/Co(1 nm)/Pt(0.6 nm). These results point to the use of electron beam evaporation as route to line-of-sight deposited, low-thickness, high quality Nb-based superspintronic multilayers.

7.
Int J Oral Maxillofac Surg ; 51(3): 332-337, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34364736

ABSTRACT

The purpose of this study was to investigate the association between habitual snoring (HS), middle ear disease (MED), and speech problems in children with cleft palate. This cross-sectional study included children aged 2.0-7.9 years with non-syndromic cleft palate anomalies. Parents completed the Pediatric Sleep Questionnaire and a questionnaire about MED. Audiograms and speech assessment were also conducted. Ninety-five children were enrolled; 15.2% of families reported HS, 97.6% MED, and 17.1% speech problems. HS (37.5% vs 10.3%, P = 0.007) and early episodes of MED (92.3% vs 58.2%, P = 0.021) were more likely to be reported for children with isolated cleft palate when compared to those with cleft lip and palate. Children with cleft lip and palate had a higher frequency of MED with effusion compared to those with Robin sequence (86.4% vs 57.1%, P = 0.049). The odds ratio for HS in children with ≥1 episode of MED in the last year was 7.37 (95% confidence interval 1.55-35.15, P = 0.012). There was a trend for children with speech problems reported by parents to have HS (30.8% vs 11.5%, P= 0.076). Anatomical factors play a role in the frequency of upper airway symptoms in children with cleft palate. A recent history of at least one episode of MED was associated with an increased frequency of HS.


Subject(s)
Cleft Lip , Cleft Palate , Ear Diseases , Child , Child, Preschool , Cleft Lip/complications , Cleft Palate/complications , Cross-Sectional Studies , Ear Diseases/complications , Humans , Snoring/complications , Snoring/epidemiology , Speech
8.
Immunohematology ; 37(4): 165-170, 2021.
Article in English | MEDLINE | ID: mdl-34964318

ABSTRACT

Some individuals are at risk of anti-D alloimmunization if they inherit D antigens that are qualitatively and/or quantitatively different than wild-type D. We hypothesized that patients who showed serologically inconsistent, weak, or historically discordant D typing results by microplate direct agglutination (MDA) on NEO or Echo (Immucor, Norcross, GA) might be at risk of carrying RHD allelic variants. The present study was designed to evaluate patients with RHD allelic variants if they presented with weakly reactive D typing results on the NEO or Echo. Patients were selected for RHD genotyping if their specimens showed weak reactivity with either series 4 or series 5 anti-D typing reagent, if the strength of reactivity was ≤1+ on the NEO or Echo, or if historical or current D typing results were discordant with current results. Patients selected for RHD genotyping were also tested by saline tube testing using the same anti-D series 4 and 5 reagents. Genotyping was performed by the Immucor genotyping laboratory in Warren, NJ. Of 80 patients whose samples met study inclusion, 52 (65.0%) were found to have RHD allelic variants. Sixteen patients (20.0%) expressed possible Ceppellini effect reactivity. Most importantly, 51.25 percent of the patients who presented with weakly reactive D typing results by MDA testing on the NEO (≤1+) or Echo (≤1+) had RHD allelic variants that were associated with the potential for anti-D alloimmunization. Laboratories that use MDA testing on the Neo or Echo for D typing should consider that female patients of childbearing age might be at risk of anti-D alloimmunization if they are classified as D+ based on weakly reactive D typing results.Some individuals are at risk of anti-D alloimmunization if they inherit D antigens that are qualitatively and/or quantitatively different than wild-type D. We hypothesized that patients who showed serologically inconsistent, weak, or historically discordant D typing results by microplate direct agglutination (MDA) on NEO or Echo (Immucor, Norcross, GA) might be at risk of carrying RHD allelic variants. The present study was designed to evaluate patients with RHD allelic variants if they presented with weakly reactive D typing results on the NEO or Echo. Patients were selected for RHD genotyping if their specimens showed weak reactivity with either series 4 or series 5 anti-D typing reagent, if the strength of reactivity was ≤1+ on the NEO or Echo, or if historical or current D typing results were discordant with current results. Patients selected for RHD genotyping were also tested by saline tube testing using the same anti-D series 4 and 5 reagents. Genotyping was performed by the Immucor genotyping laboratory in Warren, NJ. Of 80 patients whose samples met study inclusion, 52 (65.0%) were found to have RHD allelic variants. Sixteen patients (20.0%) expressed possible Ceppellini effect reactivity. Most importantly, 51.25 percent of the patients who presented with weakly reactive D typing results by MDA testing on the NEO (≤1+) or Echo (≤1+) had RHD allelic variants that were associated with the potential for anti-D alloimmunization. Laboratories that use MDA testing on the Neo or Echo for D typing should consider that female patients of childbearing age might be at risk of anti-D alloimmunization if they are classified as D+ based on weakly reactive D typing results.


Subject(s)
Agglutination , Rh-Hr Blood-Group System , Alleles , Female , Genotype , Humans , Rh-Hr Blood-Group System/genetics , Saline Solution
9.
Vaccine ; 37(30): 4094-4102, 2019 07 09.
Article in English | MEDLINE | ID: mdl-31178378

ABSTRACT

Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/metabolism , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Animals , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Disease Models, Animal , Female , Immunity, Mucosal/physiology , Lung/immunology , Lung/metabolism , Lung/virology , Mice , Mice, Inbred BALB C , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods , Viral Load
10.
Andrology ; 6(1): 151-157, 2018 01.
Article in English | MEDLINE | ID: mdl-28981994

ABSTRACT

There is substantial inter-individual variability in serum testosterone levels in hypogonadal men treated with testosterone gels. We aimed to elucidate participant-level factors that contribute to inter-individual variability in testosterone levels during testosterone therapy. An exploratory aim was to determine whether polymorphisms in genes encoding testosterone-metabolizing enzymes could explain the variation in on-treatment testosterone concentrations in men who were randomized to testosterone arm in TOM Trial. We used data from three randomized trials that used 1% transdermal testosterone gels and had testosterone levels measured 2-4 weeks after randomization for dose adjustment: Testosterone in Older Men with Mobility Limitation (TOM), Effects of Testosterone on Pain Perception (TAP), and Effects of Testosterone on Atherosclerosis Progression (TEAAM). Forty-seven percent, 38%, and 9% of participants in TAP, TEAAM, and TOM trials, respectively, failed to raise testosterone levels >400 ng/dL; 6, 8, and 30% of participants had on-treatment testosterone levels >1000 ng/dL. Even after dose adjustment, there was substantial variation in on-treatment levels at subsequent study visits. Baseline characteristics (age, height, weight, baseline testosterone, SHBG, hematocrit, and creatinine) accounted for only a small fraction of the variance (<8%). Polymorphisms in SHBG and AKR1C3 genes were suggestively associated with on-treatment testosterone levels. To conclude, baseline participant characteristics account for only a small fraction of the variance in on-treatment testosterone levels investigated. Multiple dose titrations are needed to maintain on-treatment testosterone levels in the target range. The role of SHBG and AKR3C1 polymorphisms as contributors to variations in on-treatment testosterone levels should be investigated.


Subject(s)
Androgens/administration & dosage , Eunuchism/drug therapy , Testosterone/administration & dosage , Testosterone/blood , Administration, Cutaneous , Adult , Aged , Aldo-Keto Reductase Family 1 Member C3/genetics , Gels , Hormone Replacement Therapy/methods , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Randomized Controlled Trials as Topic , Sex Hormone-Binding Globulin/genetics
11.
Transbound Emerg Dis ; 65(3): 719-726, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29250933

ABSTRACT

Controlling the spread of Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), in domestic livestock is challenging. Current diagnostic methods lack sufficient sensitivity to detect subclinically infected animals, and thus, better diagnostic methods are needed. This study was carried out to investigate the diagnostic potential of two novel peptide-mediated magnetic separation (PMS)-based tests-a PMS-phage assay and PMS-culture-both of which have been developed and optimized to detect viable MAP cells in bovine milk. Individual milk samples (50 ml) were obtained from 105 "non-infected" and 40 "MAP-infected" animals (classified as such on the basis of prior faecal culture and serum-ELISA results) in three dairy herds and tested in parallel by the PMS-phage assay and PMS-culture. Diagnostic sensitivity (DSe) and specificity (DSp) of the PMS-phage and PMS-culture methods were determined relative to the MAP infection status of the animal contributing the milk sample. The PMS-based tests applied individually showed moderate DSe (PMS-culture 0.250 and PMS-phage assay 0.325) and high DSp (0.962 and 1.000, respectively). When results of the two PMS-based tests were combined, DSe increased substantially to 0.525, and the DSp was calculated to be 0.962. It was concluded that combined application of the PMS-phage assay and PMS-culture provided the most complete picture regarding the presence of viable MAP in bovine milk samples. A comprehensive validation of the PMS-based assays relative to currently used diagnostic methods (faecal culture and serum-ELISA) would be the next step in assessment of the diagnostic potential of these novel PMS-based methods.


Subject(s)
Biological Assay/methods , Milk/microbiology , Mycobacterium avium subsp. paratuberculosis/isolation & purification , Animals , Bacteriophages/physiology , Cattle , Food Contamination/analysis , Mycobacterium avium subsp. paratuberculosis/genetics , Paratuberculosis/microbiology , Peptides/chemistry , Sensitivity and Specificity
12.
Phys Rev B ; 95(10)2017 Mar.
Article in English | MEDLINE | ID: mdl-28758157

ABSTRACT

We theoretically analyze contributions from the Kondo effect to the spin polarization and spin diffusion length in all-metal nonlocal spin valves. Interdiffusion of ferromagnetic atoms into the normal metal layer creates a region in which Kondo physics plays a significant role, giving discrepancies between experiment and existing theory. We start from a simple model and construct a modified spin drift-diffusion equation which clearly demonstrates how the Kondo physics not only suppresses the electrical conductivity but even more strongly reduces the spin diffusion length. We also present an explicit expression for the suppression of spin polarization due to Kondo physics in an illustrative regime. We compare this theory to previous experimental data to extract an estimate of the Elliot-Yafet probability for Kondo spin flip scattering of 0.7 ± 0.4, in good agreement with the value of 2/3 derived in the original theory of Kondo.

13.
Osteoarthritis Cartilage ; 24(10): 1667-1681, 2016 10.
Article in English | MEDLINE | ID: mdl-27224276

ABSTRACT

BACKGROUND: Temporal and dose-response relationships between allied health (AH) and recovery in the acute phase following lower limb (LL) arthroplasty are unclear. This systematic review investigates whether early commencement, additional therapy and/or weekend AH affects length of stay (LOS) and patient outcomes in the acute phase following LL arthroplasty. METHODS: Electronic databases were searched in February 2015. Studies were included if they evaluated any of the following aspects of AH for adults following LL arthroplasty in the acute phase: Early compared to later therapy commencement; Additional therapy; or a 6- or 7-day service compared to a lesser service. RESULTS: Twenty-four studies met the inclusion criteria, of which 19 investigated effects of physical therapy (PT) alone. Earlier PT reduced LOS (WMD = -1.23 days; 95% CI, -2.16 to -0.30) and resulted in higher probability of discharge directly home (relative risk = 1.45; 95% CI, 1.26-1.67). Addition of weekend PT reduced LOS (WMD = -1.04 days; 95% CI, -1.66 to -0.41) and improved function (SMD = 0.37; 95% CI, 0.02-0.73). Increasing PT from once to twice daily did not affect LOS (WMD = -0.35 days; 95% CI, -0.96-0.26) or function (SMD = 0.31; 95% CI, -0.06-0.71). DISCUSSION: Early PT commencement and a weekend service may produce favorable outcomes following LL arthroplasty when baseline LOS is 4 days or more. Redistributing PT resources to commence as early as day of surgery regardless of weekday may accelerate postoperative recovery. Current, high quality research is needed to confirm these findings.


Subject(s)
Physical Therapy Modalities , Arthroplasty, Replacement, Knee , Humans , Length of Stay , Lower Extremity , Patient Discharge
14.
Appl Clin Inform ; 6(1): 96-109, 2015.
Article in English | MEDLINE | ID: mdl-25848416

ABSTRACT

BACKGROUND: Hospital length of stay and discharge destination are important outcome measures in evaluating effectiveness and efficiency of health services. Although hospital administrative data are readily used as a data collection source in health services research, no research has assessed this data collection method against other commonly used methods. OBJECTIVE: Determine if administrative data from electronic patient management programs are an effective data collection method for key hospital outcome measures when compared with alternative hospital data collection methods. METHOD: Prospective observational study comparing the completeness of data capture and level of agreement between three data collection methods; manual data collection from ward-based sources, administrative data from an electronic patient management program (i.PM), and inpatient medical record review (gold standard) for hospital length of stay and discharge destination. RESULTS: Manual data collection from ward-based sources captured only 376 (69%) of the 542 inpatient episodes captured from the hospital administrative electronic patient management program. Administrative data from the electronic patient management program had the highest levels of agreement with inpatient medical record review for both length of stay (93.4%) and discharge destination (91%) data. CONCLUSION: This is the first paper to demonstrate differences between data collection methods for hospital length of stay and discharge destination. Administrative data from an electronic patient management program showed the highest level of completeness of capture and level of agreement with the gold standard of inpatient medical record review for both length of stay and discharge destination, and therefore may be an acceptable data collection method for these measures.


Subject(s)
Data Collection/methods , Length of Stay/statistics & numerical data , Patient Discharge/statistics & numerical data , Data Mining , Decision Making , Female , Health Policy , Hospital Administration/statistics & numerical data , Humans , Male , Middle Aged , Outcome Assessment, Health Care
15.
BJOG ; 121(13): 1685-93, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24888772

ABSTRACT

OBJECTIVE: To assess the frequency of obstructive sleep apnoea among women with and without hypertensive disorders of pregnancy. DESIGN: Cohort study. SETTING: Obstetric clinics at an academic medical centre. POPULATION: Pregnant women with hypertensive disorders (chronic hypertension, gestational hypertension, or pre-eclampsia) and women who were normotensive. METHODS: Women completed a questionnaire about habitual snoring and underwent overnight ambulatory polysomnography. MAIN OUTCOME MEASURES: The presence and severity of obstructive sleep apnoea. RESULTS: Obstructive sleep apnoea was found among 21 of 51 women with hypertensive disorders (41%), but in only three of 16 women who were normotensive (19%, chi-square test, P=0.005). [Author correction added on 16 June 2014, after first online publication: Results mentioned in the abstract were amended.] Non-snoring women with hypertensive disorders typically had mild obstructive sleep apnoea, but >25% of snoring women with hypertensive disorders had moderate to severe obstructive sleep apnoea. Among women with hypertensive disorders, the mean apnoea/hypopnoea index was substantially higher in snorers than in non-snorers (19.9±34.1 versus 3.4±3.1, P=0.013), and the oxyhaemoglobin saturation nadir was significantly lower (86.4±6.6 versus 90.2±3.5, P=0.021). Among women with hypertensive disorders, after stratification by obesity, the pooled relative risk for obstructive sleep apnoea in snoring women with hypertension compared with non-snoring women with hypertension was 2.0 (95% CI 1.4-2.8). CONCLUSIONS: Pregnant women with hypertension are at high risk for unrecognised obstructive sleep apnoea. Although longitudinal and intervention studies are urgently needed, given the known relationship between obstructive sleep apnoea and hypertension in the general population, it would seem pertinent that hypertensive pregnant women who snore should be tested for obstructive sleep apnoea, a condition believed to cause or promote hypertension.


Subject(s)
Hypertension, Pregnancy-Induced/epidemiology , Hypertension/epidemiology , Pregnancy Complications/epidemiology , Sleep Apnea, Obstructive/epidemiology , Snoring/epidemiology , Adult , Cohort Studies , Female , Humans , Polysomnography , Pregnancy , Severity of Illness Index , Sleep Apnea, Obstructive/diagnosis , Surveys and Questionnaires , Young Adult
16.
Nat Commun ; 5: 3927, 2014 May 29.
Article in English | MEDLINE | ID: mdl-24873934

ABSTRACT

The non-local spin-valve is pivotal in spintronics, enabling separation of charge and spin currents, disruptive potential applications and the study of pressing problems in the physics of spin injection and relaxation. Primary among these problems is the perplexing non-monotonicity in the temperature-dependent spin accumulation in non-local ferromagnetic/non-magnetic metal structures, where the spin signal decreases at low temperatures. Here we show that this effect is strongly correlated with the ability of the ferromagnetic to form dilute local magnetic moments in the NM. This we achieve by studying a significantly expanded range of ferromagnetic/non-magnetic combinations. We argue that local moments, formed by ferromagnetic/non-magnetic interdiffusion, suppress the injected spin polarization and diffusion length via a manifestation of the Kondo effect, thus explaining all observations. We further show that this suppression can be completely quenched, even at interfaces that are highly susceptible to the effect, by insertion of a thin non-moment-supporting interlayer.

17.
Rev Sci Instrum ; 85(3): 035113, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24689626

ABSTRACT

A linear time-of-flight mass spectrometer is developed for the detection and chemical analysis of nanometer-sized particles originating near the Sun. Nano-dust particles are thought to be produced by mutual collisions between interplanetary dust particles slowly spiraling toward the Sun and are accelerated outward to high velocities by interaction with the solar wind plasma. The WAVES instruments on the two STEREO spacecraft reported the detection, strong temporal variation, and potentially high flux of these particles. Here we report on the optimization and the results from the detailed characterization of the instrument's performance using submicrometer sized dust particles accelerated to 8-60 km/s. The Nano Dust Analyzer (NDA) concept is derived from previously developed detectors. It has a 200 cm(2) effective target area and a mass resolution of approximately m/Δm = 50. The NDA instrument is designed to reliably detect and analyze nanometer-sized dust particles while being pointed close to the Sun's direction, from where they are expected to arrive. Measurements by such an instrument will determine the size-dependent flux of the nano-dust particles and its variations, it will characterize the composition of the nano-dust and, ultimately, it may determine their source. The flight version of the NDA instrument is estimated to be <5 kg and requires <10 W for operation.

18.
Br J Pharmacol ; 170(5): 1130-6, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23991698

ABSTRACT

BACKGROUND AND PURPOSE: To understand how anandamide transport inhibition impacts the regulation of nausea and vomiting and the receptor level mechanism of action involved. In light of recent characterization of an anandamide transporter, fatty acid amide hydrolase-1-like anandamide transporter, to provide behavioural support for anandamide cellular reuptake as a facilitated transport process. EXPERIMENTAL APPROACH: The systemic administration of the anandamide transport inhibitor ARN272 ([(4-(5-(4-hydroxy-phenyl)-3,4-diaza-bicyclo[4.4.0]deca-1(6),2,4,7,9-pentaen-2-ylamino)-phenyl)-phenylamino-methanone]) was used to evaluate the prevention of LiCl-induced nausea-induced behaviour (conditioned gaping) in rats, and LiCl-induced emesis in shrews (Suncus murinus). The mechanism of how prolonging anandamide availability acts to regulate nausea in rats was explored by the antagonism of cannabinoid 1 (CB1) receptors with the systemic co-administration of SR141716. KEY RESULTS: The systemic administration of ARN272 produced a dose-dependent suppression of nausea-induced conditioned gaping in rats, and produced a dose-dependent reduction of vomiting in shrews. The systemic co-administration of SR141716 with ARN272 (at 3.0 mg·kg(-1)) in rats produced a complete reversal of ARN272-suppressed gaping at 1.0 mg·kg(-1). SR141716 alone did not differ from the vehicle solution. CONCLUSIONS AND IMPLICATIONS: These results suggest that anandamide transport inhibition by the compound ARN272 tonically activates CB1 receptors and as such produces a type of indirect agonism to regulate toxin-induced nausea and vomiting. The results also provide behavioural evidence in support of a facilitated transport mechanism used in the cellular reuptake of anandamide.


Subject(s)
Amidohydrolases/antagonists & inhibitors , Antiemetics/pharmacology , Arachidonic Acids/metabolism , Behavior, Animal/drug effects , Endocannabinoids/metabolism , Nausea/prevention & control , Polyunsaturated Alkamides/metabolism , Vomiting/prevention & control , Amidohydrolases/metabolism , Animals , Biological Transport , Cannabinoid Receptor Antagonists/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Isoenzymes , Lithium Chloride , Male , Nausea/chemically induced , Nausea/metabolism , Nausea/psychology , Piperidines/pharmacology , Pyrazoles/pharmacology , Rats , Rats, Sprague-Dawley , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Receptor, Cannabinoid, CB1/metabolism , Rimonabant , Shrews , Vomiting/chemically induced , Vomiting/metabolism , Vomiting/psychology
19.
Int J Clin Pract ; 67(9): 895-903, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23701141

ABSTRACT

BACKGROUND AND AIM: Current treatment for irritable bowel syndrome (IBS) is suboptimal. Fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) may trigger gastrointestinal symptoms in IBS patients. Our aim was to determine whether a low FODMAP diet improves symptoms in IBS patients. METHODS: Irritable bowel syndrome patients, who had performed hydrogen/methane breath testing for fructose and lactose malabsorption and had received dietary advice regarding the low FODMAP diet, were included. The effect of low FODMAP diet was prospectively evaluated using a symptom questionnaire. Furthermore, questions about adherence and satisfaction with symptom improvement, dietary advice and diet were assessed. RESULTS: Ninety patients with a mean follow up of 15.7 months were studied. Most symptoms including abdominal pain, bloating, flatulence and diarrhoea significantly improved (p < 0.001 for all). 75.6%, 37.8% and 13.3% of patients had fructose, lactose malabsorption or small intestinal bacterial overgrowth respectively. Fructose malabsorption was significantly associated with symptom improvement (abdominal pain odds ratio (OR) 7.09 [95% confidence interval (CI) 2.01-25.0], bloating OR 8.71 (95% CI 2.76-27.5), flatulence OR 7.64 (95% CI 2.53-23.0) and diarrhoea OR 3.39 (95% CI 1.17-9.78), p < 0.029 for all). Most patients (75.6%) were adherent to the diet, which was associated with symptom improvement (abdominal pain, bloating, flatulence and diarrhoea all significantly associated with adherence, r > 0.27, p < 0.011). Most patients (72.1%) were satisfied with their symptoms. CONCLUSIONS: The low FODMAP diet shows efficacy for IBS patients. The current strategy of breath testing and dietary advice provides a good basis to understand and adhere to the diet.


Subject(s)
Irritable Bowel Syndrome/diet therapy , Malabsorption Syndromes/diet therapy , Abdominal Pain/diet therapy , Abdominal Pain/etiology , Breath Tests , Diarrhea/diet therapy , Diarrhea/etiology , Female , Flatulence/diet therapy , Flatulence/etiology , Fructose/pharmacokinetics , Fructose Intolerance/complications , Fructose Intolerance/diet therapy , Humans , Irritable Bowel Syndrome/etiology , Lactose/pharmacokinetics , Lactose Intolerance/complications , Lactose Intolerance/diet therapy , Malabsorption Syndromes/complications , Male , Middle Aged , Patient Compliance , Patient Satisfaction , Prospective Studies , Treatment Outcome
20.
Neuroscience ; 246: 382-90, 2013 Aug 29.
Article in English | MEDLINE | ID: mdl-23623990

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder primarily affecting the dopaminergic neurons in the nigrastriatal pathway resulting in debilitating motor impairment in both familial and sporadic cases. Histone deacetylase (HDAC) inhibitors have been recently implicated as a therapeutic candidate because of their ability to correct the disrupted HDAC activity in PD and other neurodegenerative diseases. Sodium butyrate (SB), an HDAC inhibitor, reduces degeneration of dopaminergic neurons in a mutant alpha-synuclein Drosophila transgenic model of familial PD. Chronic exposure to the pesticide rotenone also causes selective degeneration of dopaminergic neurons and causes locomotor impairment and early mortality in a Drosophila model of chemically induced PD. This study investigated the effects of sodium butyrate on locomotor impairment and early mortality in a rotenone-induced PD model. We show that treatment with 10mM SB-supplemented food rescued the rotenone-induced locomotor impairment and early mortality in flies. Additionally, flies with the genetic knockdown of HDAC activity through Sin3A loss-of-function mutation (Sin3A(lof)) were resistant to rotenone-induced locomotor impairment and early mortality. Furthermore, SB-supplemented Sin3A(lof) flies had a modest additive effect for improving locomotor impairment. We also show SB-mediated improvement of rotenone-induced locomotor impairment was associated with elevated dopamine levels in the brain. However, the possibility of SB-mediated protective role through mechanisms independent from dopamine system is also discussed. These findings demonstrate that HDAC inhibitors like SB can ameliorate locomotor impairment in a rotenone-induced PD model.


Subject(s)
Butyric Acid/therapeutic use , Disease Models, Animal , Motor Activity/drug effects , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/drug therapy , Rotenone/toxicity , Animals , Animals, Genetically Modified , Butyric Acid/pharmacology , Drosophila , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , Motor Activity/physiology , Parkinson Disease, Secondary/mortality , Pesticides/toxicity
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