Effects of Environmental Water Absorption by Solution-Deposited Al2O3 Gate Dielectrics on Thin Film Transistor Performance and Mobility.

In recent years, many solution-processed oxide transistors have been reported with mobility rivaling or exceeding their vacuum-deposited counterparts. Here, we show that water absorption from the environment by solution-processed dielectric materialsexplains this enhanced mobility. By monitoring the water content of Al2O3, ZrO2, and bilayer dielectric materials, we demonstrate how water absorption by the dielectric affects electrical characteristics in solution-processed metal oxide transistors. These effects, including capacitance-frequency dispersion, counterclockwise hysteresis in transfer curves, and high channel mobility, are elucidated by electron transfer between the gate/channel and trap states within the band gap of the dielectric created by the water.

Propensity to 'relapse' following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei.

The thalamus is considered an important interface between the ventral striatopallidum and the dorsal striatum, and may therefore contribute to compulsive drug-seeking behaviour. Recent evidence suggests that the paraventricular thalamus (PVT), a dorsal midline thalamic nucleus, and the mediodorsal thalamus (MD) are involved in drug self-administration and respond to drug-associated cues. At present, however, the role of these thalamic regions in mediating cue-induced reinstatement of cocaine-seeking is unclear. Similarly, the habenula complex, part of the epithalamus, has been implicated in nicotine self-administration and cue-induced reinstatement of heroin seeking, but the role of this region in cocaine reinstatement behaviour has received little attention. Rats (n=20) were trained to self-administer cocaine in the presence of discriminative stimuli associated with drug availability (S⁺) or drug non-availability (S⁻). Once a stable level of responding was reached, lever pressing was extinguished. Animals were then tested for reinstatement and sacrificed immediately following the presentation of either the S⁻ or S⁺ discriminative stimuli, and Fos-protein expression was assessed in thalamic and epithalamic regions. Interestingly, significant variation was observed in reinstatement behaviour, allowing a comparison between high-reinstating (HR), low-reinstating (LR) and control animals. Compared with LR animals, HR animals exhibited increased Fos-protein expression in the PVT, intermediodorsal thalamus and the medial and lateral divisions of the habenula. Our data provide evidence that activation of thalamic and epithalamic nuclei is associated with propensity to reinstate to cocaine-seeking elicited by drug-related cues. We also build upon existing data highlighting the importance of the PVT in reinstatement behaviour.

Estimating the frequency of Asian cytochrome B haplotypes in standard European and local Spanish pig breeds.

Mitochondrial DNA has been widely used to perform phylogenetic studies in different animal species. In pigs, genetic variability at the cytochrome B gene and the D-loop region has been used as a tool to dissect the genetic relationships between different breeds and populations. In this work, we analysed four SNP at the cytochrome B gene to infer the Asian (A1 and A2 haplotypes) or European (E1 and E2 haplotypes) origins of several European standard and local pig breeds. We found a mixture of Asian and European haplotypes in the Canarian Black pig (E1, A1 and A2), German Piétrain (E1, A1 and A2), Belgian Piétrain (E1, A1), Large White (E1 and A1) and Landrace (E1 and A1) breeds. In contrast, the Iberian (Guadyerbas, Ervideira, Caldeira, Campanario, Puebla and Torbiscal strains) and the Majorcan Black pig breeds only displayed the E1 haplotype. Our results show that the introgression of Chinese pig breeds affected most of the major European standard breeds, which harbour Asian haplotypes at diverse frequencies (15-56%). In contrast, isolated local Spanish breeds, such as the Iberian and Majorcan Black pig, only display European cytochrome B haplotypes, a feature that evidences that they were not crossed with other Chinese or European commercial populations. These findings illustrate how geographical confinement spared several local Spanish breeds from the extensive introgression event that took place during the 18th and 19th centuries in Europe.

Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma.

This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.

A large duplication associated with dominant white color in pigs originated by homologous recombination between LINE elements flanking KIT.

The Dominant White (I/KIT) locus is one of the major coat color loci in the pig. Previous studies showed that the Dominant White (I) and Patch (IP) alleles are both associated with a duplication including the entire KIT coding sequence. We have now constructed a BAC contig spanning the three closely linked tyrosine kinase receptor genes PDGFRA-KIT-KDR. The size of the duplication was estimated at about 450 kb and includes KIT, but not PDGFRA and KDR. Sequence analysis revealed that the duplication arose by unequal homologous recombination between two LINE elements flanking KIT. The same unique duplication breakpoint was identified in animals carrying the I and IP alleles across breeds, implying that Dominant White and Patch alleles are descendants of a single duplication event. An unexpected finding was that Piétrain pigs carry the KIT duplication, since this breed was previously assumed to be wild type at this locus. Comparative sequence analysis indicated that the distinct phenotypic effect of the duplication occurs because the duplicated copy lacks some regulatory elements located more than 150 kb upstream of KIT exon 1 and necessary for normal KIT expression.

Salmeterol/fluticasone propionate combination therapy 50/250 microg twice daily is more effective than budesonide 800 microg twice daily in treating moderate to severe asthma.

Three hundred and fifty-three asthmatic patients who remained symptomatic despite treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized to a new combination therapy comprising salmeterol 50 microg and fluticasone propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of their morning and evening peak expiratory flow (PEF), daytime and night-time symptom scores and daytime and night-time use of rescue salbutamol. Mean morning PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1) (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P < 0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided significantly better control of daytime symptoms and a significantly greater reduction in the requirement for rescue salbutamol compared with budesonide. These results demonstrate that SFC 50/250 microg twice daily is superior to budesonide 800 microg twice daily in the management of patients with moderate to severe asthma who are symptomatic on their existing dose of corticosteroid.

Oral sumatriptan: effect of a second dose, and incidence and treatment of headache recurrences.

Oral sumatriptan in a dose of 100 mg aborts about 60% of migraine attacks within 2 h, but the headache may recur within 24 h. We investigated: (i) the incidence of headache recurrence after oral sumatriptan (ii) whether a second tablet of sumatriptan at 2 h increases initial efficacy and/or (iii) prevents headache recurrence and (iv) whether a further tablet of sumatriptan treats headache recurrence. In a randomized parallel-group clinical trial, 1246 patients treated one to three migraine attacks (with or without aura), with 100 mg oral sumatriptan. Two hours later they all took a double-blind randomized second table of sumatriptan (group I) or placebo (group II). Patients who initially improved, but then experienced headache recurrence took a further double-blind randomized tablet of sumatriptan or placebo. Proportions of patients who improved from moderate/severe headache to mild/none were similar in groups I and III at 2 h (55 vs 56%) and 4 h (80 vs 77%). Incidences of headache recurrence (moderate/severe-any grade of headache) and median times to headache recurrence were also similar: 22-32% at 16 h in group I and 25-33% at 16.5 h in group II. Sumatriptan was superior to placebo in treating headache recurrence: 74 vs 49% (p = 0.017) in group I and 70 vs 30% (p = 0.0001) in group II. Thus, one-fourth of patients experience headache recurrence at about 16 h after successful treatment of a migraine attack with 100 mg oral sumatriptan. A second tablet of sumatriptan at 2 h does not increase initial efficacy and neither prevents nor delays headache recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Stress induces an increased hexose uptake in cultured cells.

Temperature-sensitive mutants have revealed a region of the herpes simplex virus 1 genome that affects both the uptake of hexose and the synthesis of heat shock proteins. Other inducers of heat-shock proteins, namely heat shock itself and arsenite, likewise induce an increased uptake of hexose. The increased uptake, like that induced by insulin, is insensitive to the presence of actinomycin D or cycloheximide. It is concluded that an increased hexose uptake, reflecting an activation or relocation of existing hexose transport protein, is a general biochemical response of stressed cells.

Changes in excitability induced by herpes simplex viruses in rat dorsal root ganglion neurons.

The physiological properties of rat sensory neurons infected with herpes simplex type 1 viruses and maintained in cell culture were studied using intracellular recording techniques. Two syncytial (cell fusing) and two nonsyncytial strains of virus were examined; individual strains of virus had different effects on neuronal excitability. The nonsyncytial viruses caused a loss of tetrodotoxin-sensitive low-threshold action potentials and blocked hyperpolarization-activated inward rectification, but did not alter the resting membrane potential, depolarization-activated outward rectification, or render the cells leaky. These effects develop progressively over the period 5-15 hr postinfection. One syncytial strain of virus induced spontaneous electrical activity that appeared to be the result of discrete electrical coupling between sensory neuron processes; as a result, action potential discharge is synchronized in coupled neurons. A second syncytial strain of virus rendered neurons inexcitable; however, in these experiments the input resistance fell to low values, possibly as a result of extensive coupling between sensory neurons. Viral replication in sensory neurons was demonstrable with indirect immunofluorescence using an antibody to herpes simplex viruses and correlated with the onset of virally induced changes in excitability. Virally triggered changes in excitability were blocked by the specific herpes virus antimetabolite acyclovir, suggesting that viral adsorption and penetration are by themselves insufficient to evoke changes in excitability. These results suggest that herpes viruses have selective effects on the excitable mechanisms in sensory neurons that are not simply the result of a general loss of membrane conductances or the disruption of transmembrane ion gradients.

Increased sugar transport in BHK cells infected with Semliki Forest virus or with herpes simplex virus.

Infection of BHK cells by SFV increases the rate of uptake of [3H]MeGlc and of [3H]dGlc at approximately 2 hours p.i. Infection by HSV increases the uptake of [3H]MeGlc and [3H]dGlc at approximately 10 hours p.i.; the increased uptake is prevented by acyclovir. It is concluded that an increased sugar uptake by infected cells reflects an increased rate of transport across the plasma membrane and is the result of cellular changes caused by virus infection.

Spontaneous electrical activity induced by herpes virus infection in rat sensory neuron cultures.

Dissociated cultures of rat dorsal root ganglion neurons were infected with a syncytial strain of herpes simplex virus type 1. Over 90% of neurons in infected cultures were spontaneously active and fired action potentials which, on membrane potential hyperpolarization, were replaced by depolarizing events similar to excitatory postsynaptic potentials. Amplitude analysis of these events produced populations described by the sum of several unitary events with Gaussian rather than binomial or Poisson distributions. Such spontaneous activity was blocked by tetrodotoxin but not by low calcium high magnesium solutions containing cadmium. Simultaneous recording from pairs of spontaneously active neurons revealed excitatory connexions between cells. It is suggested that virus-induced fusion of nerve cell processes induces electrical coupling between sensory neurons, and that the resulting electrical network supports spontaneous activity.

Social support and post-burn adjustment.

Interviews were conducted with 314 persons who had sustained burns and were treated at a major burn center between 1956 and 1976. The interviews covered standard socioeconomic data and post-burn life patterns including the number of weeks lost to employment or education. The data indicate that social support is both directly and indirectly related to patients' post-burn adjustment. Measures of social support from family, friends, and peers were significantly related to several subjectively assessed outcomes, such as life satisfaction, self-esteem and participation in social and recreational activities. There was also evidence that social support moderates the rehabilitation process independent of the severity of the burn injury. The findings tend to challenge the commonly held belief that psychosocial rehabilitation needs are monotonically related to the severity of the injury.

Self-esteem of severely burned patients.

As a part of a retrospective rehabilitation study conducted in 1977, 320 persons treated at a major burn center between 1956 and 1976 were interviewed by professional survey research interviewers using a specially developed 519-item questionnaire that included standard socioeconomic data along with information about the person's life pattern subsequent to the burn. In addition, several complex dimensions of personality were measured through multiple indicators rather than by single items. According to the midpoint of the scale of Coopersmith's Self-Esteem Inventory, 85% of the respondents had adequate to high self-esteem. Although the size of the burn and part of the body burned did not seem to significantly affect self-esteem, age when burned and time since burn did. Disfigured females had significantly lower self-esteem than disfigured males. Social support, life satisfaction, involvement in social and recreational activities and employment were found to influence the group as a whole. Respondents with low self-esteem spent twice as many days in bed and missed considerably more days of work in the year prior to the study than did those with moderate or high self-esteem. The findings in this study indicate with some certainty that the majority of burned people make a successful adjustment following even large and disfiguring injuries and that successful rehabilitation is long-term and episodic in nature.

The planning and organization of a regionalized burn care system.

The burn problem in the United States, as reflected in published data, is serious. More than 2,000,000 people are injured in burn accidents each year; 70,000 are hospitalized, involving approximately 9,000,000 disability days; and an estimated 9,000 die from their injuries. In 1964, the National Burn Information Exchange (NBIE) was established in Michigan. NBIE collects national and international data representing currently 40,000 burn cases from 133 hospitals in the United States, Canada and overseas. NBIE provides information or morbidity by etiology, treatment patterns and mortality by cause and institution. The organized data are a major and valuable information resource helpful for establishing criteria and policy guidelines for organizing burn care services based on need, severity, and quality measures as reflected by outcomes of care. Based on NBIE analyses of current information, it is recommended 1) that only 10 per cent of the acute general hospitals in the United States need be involved directly in the provision of specialized burn patient care; 2) that 3 levels of care be established as determined by severity of injury and intensity of care; and 3) that burn care should be organized within a comprehensive regionalized Emergency Medical Service (EMS) system in accordance with the EMS Act of 1973 and the 1976 amendments.

Functional changes in autonomic nervous responses with ageing.

The effects of ageing on autonomic nervous responses have been investigated in 29 young adults, 64 healthy elderly in the age range 66 to 86 years, and 20 elderly in-patients with hypothermia, instability of bladder function or marked orthostatic hypotension. In the healthy elderly group, the beat-to-beat variation in response to postural change was significantly diminished, the vasoconstrictor response to cooling reduced and baroreflex sensitivity during lower-body negative pressure was decreased compared with young adults. Patients with an atronic bladder, determined by urodynamic tests, showed an even more marked decrease in baroreflex sensitivity. The multisystem nature of these autonomic disturbances suggests that physiological impairment may occur in autonomic neural pathways with ageing.