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K Graham

Publications and source records attributed to K Graham.

At least 19 recordsLinked to original sources
PubMed2002

Direct evidence for neutrino flavor transformation from neutral-current interactions in the Sudbury Neutrino Observatory.

Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.

Journal Article↗
PubMed2002

Measurement of day and night neutrino energy spectra at SNO and constraints on neutrino mixing parameters.

The Sudbury Neutrino Observatory (SNO) has measured day and night solar neutrino energy spectra and rates. For charged current events, assuming an undistorted 8B spectrum, the night minus day rate is 14.0%+/-6.3%(+1.5%)(-1.4%) of the average rate. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the nu(e) asymmetry is found to be 7.0%+/-4.9%(+1.3%)(-1.2%). A global solar neutrino analysis in terms of matter-enhanced oscillations of two active flavors strongly favors the large mixing angle solution.

Journal Article↗
PubMed2002

Comparison of three pyrethroid treatments of top-sheets for malaria control in emergencies: entomological and user acceptance studies in an Afghan refugee camp in Pakistan.

Insecticide-treated bedding materials (sheets and blankets) could be protective against vectors of malaria and leishmaniasis--especially in complex emergencies, epidemics and natural disasters where people are more likely to sleep in exposed situations. Comparison of cotton top-sheets impregnated with different pyrethroids (permethrin 500 mg/m2, deltamethrin 25 mg/m2 or alphacypermethrin 25 mg/m2) for effectiveness against mosquitoes (Diptera: Culicidae) was undertaken in a refugee camp in Pakistan. Predominant species encountered were Anopheles stephensi Liston, An. pulcherrimus Theobald, An. nigerrimus Giles, Culex quinquefasciatus Say, Cx. tritaeniorhynchus Giles and other culicine mosquitoes. All three pyrethroid treatments performed significantly better than the untreated sheets in deterrence and killing of mosquitoes. No significant differences were found between the three insecticides tested in terms of entomological effect. Washing of the treated sheets greatly reduced their effectiveness. In a user acceptance study conducted among 88 families (divided into four groups), six families complained of irritation of the skin and mucous membranes. Of these reports, one was from the placebo group (using untreated sheets) and the other five (5/22=23%) from families using deltamethrin-treated sheets. All families allocated to permethrin and alphacypermethrin groups declared an appreciation for the intervention and reported no side-effects. Ten of the placebo group disliked the intervention, citing no prevention of mosquito biting as the reason. Side-effects associated with deltamethrin indicate that alphacypermethrin and permethrin are more appropriate first choice insecticides for treatment of sheets and blankets.

Afghanistan↗
PubMed2002

Insecticide-treated plastic tarpaulins for control of malaria vectors in refugee camps.

Spraying of canvas tents with residual pyrethroid insecticide is an established method of malaria vector control in tented refugee camps. In recent years, plastic sheeting (polythene tarpaulins) has replaced canvas as the utilitarian shelter material for displaced populations in complex emergencies. Advances in technology enable polythene sheeting to be impregnated with pyrethroid during manufacture. The efficacy of such material against mosquitoes when erected as shelters under typical refugee camp conditions is unknown. Tests were undertaken with free-flying mosquitoes on entomological study platforms in an Afghan refugee camp to compare the insecticidal efficacy of plastic tarpaulin sprayed with deltamethrin on its inner surface (target dose 30 mg/m2), tarpaulin impregnated with deltamethrin (initially > or = 30 mg/m2) during manufacture, and a tent made from the factory impregnated tarpaulin material. Preliminary tests done in the laboratory with Anopheles stephensi Liston (Diptera: Culicidae) showed that 1-min exposure to factory-impregnated tarpaulins would give 100% mortality even after outdoor weathering in a temperate climate for 12 weeks. Outdoor platform tests with the erected materials (baited with human subjects) produced mosquito mortality rates between 86-100% for sprayed or factory-impregnated tarpaulins and tents (average approximately 40 anophelines and approximately 200 culicines/per platform/night), whereas control mortality (with untreated tarpaulin) was no more than 5%. Fewer than 20% of mosquitoes blood-fed on human subjects under either insecticide-treated or non-treated shelters. The tarpaulin shelter was a poor barrier to host-seeking mosquitoes and treatment with insecticide did not reduce the proportion blood-feeding. Even so, the deployment of insecticide-impregnated tarpaulins in refugee camps, if used by the majority of refugees, has the potential to control malaria by killing high proportions of mosquitoes and so reducing the average life expectancy of vectors (greatly reducing vectorial capacity), rather than by directly protecting refugees from mosquito bites. Mass coverage with deltamethrin-sprayed or impregnated tarpaulins or tents has strong potential for preventing malaria in displaced populations affected by conflict.

Afghanistan↗
PubMed2001

Expression of high Km 5'-nucleotidase in leukemic blasts is an independent prognostic factor in adults with acute myeloid leukemia.

Cytarabine (ara-C) requires activation into its triphosphorylated form, ara-CTP, to exert cytotoxic activity. Cytoplasmic 5'-nucleotidase (5NT) dephosphorylates ara-CMP, a key intermediate, preventing accumulation of ara-CTP and may reduce cellular sensitivity to the cytotoxic activity of ara-C. To determine whether the level of expression of 5NT is correlated with clinical outcome in patients with acute myeloid leukemia (AML) treated with ara-C, this study analyzed the levels of messenger RNA expression of high Km 5NT by real-time polymerase chain reaction at diagnosis in blast cells of 108 patients with AML. High Km 5NT was expressed at diagnosis in the blast cells of 54% of patients. In univariate analysis, (1) patients whose blast cells contained high levels (values greater than the median value for total population) of high Km 5NT at diagnosis had significantly shorter disease-free survival (DFS) than patients with low levels of high Km 5NT (11 months versus 17.5 months, P =.02) and (2) high levels of high Km 5NT also predicted significantly shorter overall survival (15.7 months versus 39 months, P = .01) in young patients (< or = 57 years; median value for the entire population). In a multivariate analysis taking into account age, karyotype risk, and other factors found to have prognostic significance in univariate analysis, (1) high Km 5NT expression was an independent prognostic factor for DFS and (2) high levels of high Km 5NT also predicted significantly shorter overall survival in young patients. These results demonstrate that the expression of high levels of high Km 5NT in blast cells is correlated with outcome in patients with AML.

5'-Nucleotidase↗
PubMed2001

Differing patterns of temporal atrophy in Alzheimer's disease and semantic dementia.

OBJECTIVE: To characterize and quantify the patterns of temporal lobe atrophy in AD vs semantic dementia and to relate the findings to the cognitive profiles. Medial temporal lobe atrophy is well described in AD. In temporal variant frontotemporal dementia (semantic dementia), clinical studies suggest polar and inferolateral temporal atrophy with hippocampal sparing, but quantification is largely lacking. METHODS: A volumetric method for quantifying multiple temporal structures was applied to 26 patients with probable AD, 18 patients with semantic dementia, and 21 matched control subjects. RESULTS: The authors confirmed the expected bilateral hippocampal atrophy in AD relative to controls, with involvement of the amygdala bilaterally and the right parahippocampal gyrus. Contrary to expectations, patients with semantic dementia had asymmetric hippocampal atrophy, more extensive than AD on the left. As predicted, the semantic dementia group showed more severe involvement of the temporal pole bilaterally and the left amygdala, parahippocampal gyrus (including the entorhinal cortex), fusiform gyrus, and the inferior and middle temporal gyri. Performance on semantic association tasks correlated with the size of the left fusiform gyrus, whereas naming appeared to depend upon a wider left temporal network. Episodic memory measures, with the exception of recognition memory for faces, did not correlate with temporal measures. CONCLUSIONS: Hippocampal atrophy is not specific for AD but is also seen in semantic dementia. Distinguishing the patients with semantic dementia was the severe global but asymmetric (left > right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral temporal gyri. These findings have implications for diagnosis and understanding of the cognitive deficits in AD and semantic dementia.

Aged↗
PubMed2001

Depression of transmitter release at synapses in the rat superior cervical ganglion: the role of transmitter depletion.

The characteristics of depression of the excitatory postsynaptic potential (EPSP) during a short train of impulses to the rat superior cervical ganglion (SCG) have been ascertained with the object of determining the relative contributions of transmitter depletion and autoreceptors to depression. Successive EPSPs in a short train were depressed after the first (Vo) up to about the fourth impulse when a steady-state depressed EPSP level (Vss) was reached. Vss increased with the stimulation frequency between 1 and 30 Hz. Vo recovered after a short train with a time constant of about 2.8 s in the frequency range from 5 to 30 Hz. In order to determine if depression was related to changes in calcium influx with successive impulses in the train. preganglionic boutons were loaded with the calcium indicator Oregon Green 488 BAPTA-1 and line scans taken through individual boutons with a confocal laser microscope. Successive calcium transients were of about the same amplitude in boutons during short trains of impulses at 5 Hz. The contribution of autoreceptors activated by the action of endogenously derived adenosine on the extent of depression of the EPSP during short trains was ascertained by blocking these receptors with 8-phenyltheophylline (10 microM). There was no change in the extent or time course of development of depression. Similar results were obtained with the opioid receptor antagonist naloxone (10 microM) and the adrenergic receptor antagonist yohimbine (10 microM). Factors, which increased the extent of transmitter release during a train, such as increasing the external calcium concentration from 0.8 to 2.5 mM, increased depression. Factors. which decreased the extent of transmitter release such as increasing the exogenous adenosine concentration between 1 and 200 microM decreased depression. These results are interpreted in terms of a model in which vesicles are mobilised by a calcium-dependent process from a store into an available pool of docked vesicles. Depletion of the docked vesicles during exocytosis then leads to depression of transmitter release during a train of impulses.

Animals↗
PubMed2001

Steps towards constructing a global comparative risk analysis for alcohol consumption: determining indicators and empirical weights for patterns of drinking, deciding about theoretical minimum, and dealing with different consequences.

In order to conduct a comparative risk analysis for alcohol within the Global Burden of Disease Study (GBD 2000), several questions had to be answered. (1) What are the appropriate dimensions for alcohol consumption and how can they be categorized? The average volume of alcohol and patterns of drinking were selected as dimensions. Both dimensions could be looked upon as continuous but were categorized for practical purposes. The average volume of drinking was categorized into the following categories: abstention; drinking 1 (> 0-19.99 g pure alcohol daily for females, > 0-39.99 g for males); drinking 2 (20-39.99 g for females, 40-59.99 g for males), and drinking 3 (> or =40 g for females, > or =60 g for males). Patterns of drinking were categorized into four levels of detrimental impact based on an optimal scaling analysis of key informant ratings. (2) What is the theoretical minimum for both dimensions? A pattern of regular light drinking (at most 1 drink every day) was selected as theoretical minimum for established market economies for all people above age 45. For all other regions and age groups, the theoretical minimum was set to zero. Potential problems and uncertainties with this selection are discussed. (3) What are the health outcomes for alcohol and how do they relate to the dimensions? Overall, more than 60 disease conditions were identified as being related to alcohol consumption. Most chronic conditions seem to be related to volume only (exceptions are coronary heart disease and ischemic stroke), and most acute conditions seem to be related to volume and patterns. In addition, using methodology based on aggregate data, patterns were relevant for attributing harms for men but not women.

Adolescent↗
PubMed2000

Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib).

The human concentrative (Na(+)-linked) plasma membrane transport proteins hCNT1 and hCNT2 are selective for pyrimidine nucleosides (system cit) and purine nucleosides (system cif), respectively. Both have homologs in other mammalian species and belong to a gene family (CNT) that also includes hfCNT, a newly identified broad specificity pyrimidine and purine Na(+)-nucleoside symporter (system cib) from the ancient marine vertebrate, the Pacific hagfish (Eptatretus stouti). We now report the cDNA cloning and characterization of cib homologs of hfCNT from human mammary gland, differentiated human myeloid HL-60 cells, and mouse liver. The 691- and 703-residue human and mouse proteins, designated hCNT3 and mCNT3, respectively, were 79% identical in amino acid sequence and contained 13 putative transmembrane helices. hCNT3 was 48, 47, and 57% identical to hCNT1, hCNT2, and hfCNT, respectively. When produced in Xenopus oocytes, both proteins exhibited Na(+)-dependent cib-type functional activities. hCNT3 was electrogenic, and a sigmoidal dependence of uridine influx on Na(+) concentration indicated a Na(+):uridine coupling ratio of at least 2:1 for both hCNT3 and mCNT3 (cf 1:1 for hCNT1/2). Phorbol myristate acetate-induced differentiation of HL-60 cells led to the parallel appearance of cib-type activity and hCNT3 mRNA. Tissues containing hCNT3 transcripts included pancreas, bone marrow, trachea, mammary gland, liver, prostate, and regions of intestine, brain, and heart. The hCNT3 gene mapped to chromosome 9q22.2 and included an upstream phorbol myristate acetate response element.

Amino Acid Sequence↗
PubMed2000

Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription.

Induction of NF-kappaB-dependent transcription requires phosphorylation and subsequent degradation of I-kappaB, an inhibitor of NF-kappaB, followed by nuclear translocation and DNA binding of NF-kappaB. Tumor necrosis factor receptor-associated factor 2 (TRAF2) plays a role in NF-kappaB activation in response to cytokines such as tumor necrosis factor alpha (TNFalpha). In this study, we purified and characterized a novel kinase (T2K, also known as TBK1 or NAK), which associates with TRAF2 and exhibits kinase activity towards I-kappaBalpha in vitro. The physiological function of T2K was investigated using T2K-deficient mice. Heterozygotes appear normal, but t2k(-/-) animals die at approximately E14.5 of massive liver degeneration and apoptosis. Never theless, hematopoietic progenitors from T2K-deficient fetal liver support normal lymphocyte development. Furthermore, t2k(-/-) embryonic fibroblasts and thymocytes do not display increased sensitivity to TNFalpha-induced apoptosis. In response to either TNFalpha or IL-1 induction, t2k(-/-) embryonic fibroblasts exhibit normal degradation of I-kappaB and kappaB-binding activity. However, NF-kappaB-directed transcription is dramatically reduced. These results demonstrate that, like I-kappaB kinase beta and the RelA subunit of NF-kappaB, T2K is critical in protecting embryonic liver from apoptosis. However, T2K has a unique role in the activation of NF-kappaB-directed transcription, apparently independent of I-kappaB degradation and NF-kappaB DNA binding.

Amino Acid Sequence↗
PubMed2000

Characterizing and dating the onset of symptoms in psychotic illness: the Symptom Onset in Schizophrenia (SOS) inventory.

Prodromal symptoms, including disturbances of perceptions, beliefs, cognition, affect, and behavior, are often the first symptoms of schizophrenia. Little is understood about the initial, prodromal stage of schizophrenia, despite the compelling research and clinical need. The development and psychometric properties of a new, time-efficient instrument to characterize and date the initial symptoms of a psychotic illnesses, the Symptom Onset in Schizophrenia (SOS) scale, is described in this paper. The SOS rates the presence and dates the onset of 16 general prodromal, positive, negative, and disorganizational symptoms, as well as a clinician, family, and patient global rating of onset of illness. Inter-rater reliability for the presence of each symptom in 35 patients with schizophrenia, schizoaffective, or schizophreniform disorder was good to excellent, with kappa coefficient >0.7 for 12 items, and >0. 5 for all items. Agreement on symptom duration was good to excellent for individual items (ICC=0.7-1.0) and for global rating of duration of illness (ICC=0.97). Our data indicate that the SOS is a reliable, valid, time-efficient tool useful to retrospectively assess the onset of schizophrenia and related psychotic disorders. Further study is underway to evaluate other psychometric properties of the SOS, including test-retest reliability and predictive validity.

Adult↗
PubMed2000

M11L: a novel mitochondria-localized protein of myxoma virus that blocks apoptosis of infected leukocytes.

M11L, a novel 166-amino acid membrane-associated protein expressed by the poxvirus, myxoma virus, was previously found to modulate apoptosis after infection of rabbit leukocytes. Furthermore, infection of rabbits with an M11L knockout virus unexpectedly produced lesions with a profound proinflammatory phenotype. We show here that M11L is antiapoptotic when expressed independently of other viral proteins, and is directed specifically to mitochondria by a short COOH-terminal region that is necessary and sufficient for targeting. This targeting region consists of a hydrophobic domain flanked by basic amino acid residues, adjacent to a positively charged tail. M11L blocks staurosporine-induced apoptosis by preventing mitochondria from undergoing a permeability transition, and the mitochondrial localization of this protein is essential for this function. We show that M11L is specifically required to inhibit the apoptotic response of monocytes/macrophages during virus infection, as cells of this lineage undergo apoptosis when infected with the M11L knockout virus. As monocyte apoptosis is uniquely proinflammatory, we propose that this observation reconciles the paradoxical proapoptotic and proinflammatory phenotypes of the M11L knockout virus. We suggest that apoptosis of tissue macrophages represents an important antiviral defense, and that the inhibition of apoptosis by viral proteins can be directed in a cell-specific fashion.

Amino Acid Sequence↗
PubMed2000

Post-translational modification of the myxoma-virus anti-inflammatory serpin SERP-1 by a virally encoded sialyltransferase.

SERP-1 is a secreted serpin (serine-proteinase inhibitor) encoded by myxoma virus, a poxvirus pathogen of rabbits. SERP-1 is required for myxoma-virus virulence, and the purified protein has been shown to possess independent anti-inflammatory activity in animal models of restenosis and antigen-induced arthritis. As an inhibitor of serine proteinases, SERP-1 acts against tissue-type plasminogen activator, urokinase-type plasminogen activator, plasmin, thrombin and Factor Xa. In the present study, examination of SERP-1 glycosylation-site mutants showed that the N-linked glycosylation of Asn(172) was essential for SERP-1 secretion, whereas mutation of Asn(99) decreased secretion efficiency, indicating that N-linked glycosylation plays an essential role in the processing and trafficking of SERP-1. Furthermore, comparison of SERP-1 from wild-type myxoma virus and a virus containing a targeted disruption of the MST3N sialyltransferase locus demonstrated that SERP-1 is specifically modified by this myxoma-virus-encoded sialyltransferase, and is thus the first reported viral protein shown to by modified by a virally encoded glycosyltransferase. Sialylation of SERP-1 by the MST3N gene product creates a uniquely charged species of secreted SERP-1 that is distinct from SERP-1 produced from other eukaryotic expression systems, though this has no apparent effect upon the kinetics of in vitro proteinase inhibition. Rather, the role of viral sialylation of SERP-1 likely relates to masking antigenicity or targeting SERP-1 to specific sites of action in vivo.

Amino Acid Sequence↗
PubMed2000

Gender differences in alcohol consumption and adverse drinking consequences: cross-cultural patterns.

AIMS: To examine the consistency and/or variability of gender differences in drinking behavior cross-culturally. DESIGN, SETTING, PARTICIPANTS: Women's and men's responses in 16 general population surveys from 10 countries, analyzed by members of the International Research Group on Gender and Alcohol. MEASUREMENTS: Comparable measures of drinking, versus abstention, typical drinking frequencies and quantities, heavy episodic drinking, intoxication, morning drinking, and alcohol-related family and occupational problems. FINDINGS: Women and men differed little in the probability of currently drinking versus abstaining, but men consistently exceeded women in typical drinking frequencies and quantities and in rates of heavy drinking episodes and adverse drinking consequences, while women were consistently more likely than men to be life-time abstainers. In older age groups, both men and women drank smaller quantities of alcohol and were more likely to stop drinking altogether, but drinking frequencies did not change consistently with age. CONCLUSIONS: A theoretical synthesis proposes that gender roles may amplify biological differences in reactions to alcohol, and that gender differences in drinking behavior may be modified by macrosocial factors that modify gender role contrasts.

Adult↗
PubMed2000

Evaluating theories of alcohol-related aggression using observations of young adults in bars.

AIMS: The objective of the present study is to evaluate 36 explanations of alcohol-related aggression that have been proposed in the research literature in terms of their relevance to naturally-occurring incidents of aggression involving alcohol. DESIGN: The study involved content analysis of descriptions of 105 incidents of aggression. SETTING AND PARTICIPANTS: Bars frequented by young adults. MEASUREMENTS: Step-by-step descriptions of incidents of aggression reported by researcher-observers based on 93 nights of observation in bars between midnight and 3 a.m. FINDINGS: Some explanations relating to the effects of alcohol (e.g. focused on the present, reduced anxiety about sanctions or danger, heightened emotionality) and the environment (e.g. generally permissive environment, expectation by patrons that aggression will be tolerated) were found to be relevant to most incidents, while other explanations (e.g. crowding, release of pent-up anger) were directly relevant to only a few or no incidents. Incidents involving male-to-male aggression were more likely than incidents involving both males and females to be attributable to expectations, acceptance of aggression, power concerns, male honor and "macho" values. Principal components analysis identified five groupings of explanations: risk-taking effects of alcohol, cognitive impairment from alcohol, hyperemotional effects of alcohol, "macho" subculture, and permissive environment. CONCLUSIONS: The findings are consistent with a model of alcohol-related aggression that involves multiple contributing factors including alcohol effects and situational contexts. The greater relevance of certain explanations and the natural groupings of explanations point to directions for future research.

Adolescent↗
PubMed2000

Alcohol-related aggression in the general population.

OBJECTIVE: This study estimates the relationships between drinking in the event and drinking patterns and different levels of aggression severity. METHOD: A telephone survey of 1,001 adults (542 women) age 18 and over was conducted (response rate of 67%) using computer assisted telephone interviewing (CATI). Respondents were asked whether they had been personally involved in a serious argument, an incident involving threat, or physical aggression in the past year and whether anyone had been drinking alcohol in the most recent incident. Respondents also reported their typical alcohol consumption patterns. RESULTS: The proportion of respondents reporting involvement in serious arguments, threats or physical aggression was 19.8%, 11.8% and 12.0%, respectively. Someone in the incident had been drinking in 38.1% of serious arguments, 56.5% of threats and 67.9% of incidents of physical aggression. When gender, age, education, marital status and employment status were controlled for, high quantity drinking (as measured by the largest number of drinks consumed on one drinking occasion in the past year), overall estimated annual volume of alcohol consumed, and frequency of consuming five drinks per occasion were significantly greater for physical aggression, compared with arguments and no aggression. However, drinker status (abstainer/drinker) and frequency of drinking were not significantly associated with involvement in aggression. In a logistic regression analysis controlling for demographic variables, a composite measure of alcohol consumption was highly significant for physical aggression versus no aggression and for physical versus verbal aggression. Physical aggression was also associated with being younger, separated/ divorced and a student. CONCLUSIONS: The results suggest that alcohol intoxication, rather than mere alcohol consumption, is associated with aggression. Moreover, alcohol intoxication is more strongly associated with physical aggression than with verbal aggression.

Adolescent↗