To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Stroke thrombolysis is limited by the “last-seen well” principle, which defines stroke onset time. A significant minority of stroke patients (~15%) awake with their symptoms and are by definition ineligible for thrombolysis because they were “last-seen well” at the time they went to bed implying an interval that is most often greater than three hours.
A single-centre prospective, safety study was designed to thrombolyse 20 subjects with stroke-on-awakening. Patients were eligible for inclusion if they were last seen well less than 12 hours previously, specifically including those who awoke from sleep with their stroke deficits. They had a baseline computed tomogram (CT) scan with an ASPECTS score greater than 5, no evidence of well-evolved infarction and a CT angiogram / Trans-cranial Doppler ultrasound study demonstrating an intracranial arterial occlusion. Patients fulfilled all other standard criteria for stroke thrombolysis. The primary outcome was safety defined by symptomatic ICH or death.
Among 89 screened patients, 20 were treated with thrombolysis. Two patients (10%) died due to massive carotid territory stroke and two patients (10%) died of stroke complications. Two patients (10%) showed asymptomatic intracerebral hemorrhage (ICH) (petechial hemorrhage) and none symptomatic ICH. Reasons for exclusion were: (a) ASPECTS ≤ 5 (29); (b) well-evolved infarcts on CT (19); (c) historical mRS > 2 (17); (d) no demonstrable arterial occlusion or were too mild to warrant treatment (10).
Patients who awake with their deficits can be safely treated with thrombolysis based upon a tissue window defined by NCCT and CTA/TCD.
It has been suggested that individuals might be more readily colonized with bacteria that cause meningitis through enhanced binding of the bacteria to virusinfected epithelial cells. As respiratory syncytial virus (RSV) affects infants and children in the age group also susceptible to bacterial meningitis, we tested the hypothesis that infection of HEp-2 cells by RSV might enhance binding of Neisseria meningitidis or Haemophilus influenzae type b (Hib). Attachment of fluorescein-labelled bacteria to HEp-2 cells was measured by flow cytometry, and RSV-infected cells bound significantly more meningococci (P < 0·001) and Hib (P < 0·01) than uninfected cells. Although the isolates expressed different antigenic characteristics (3 meningococci and 5 Hib), all showed a similar pattern of binding. The results are discussed with reference to the methods used for detection of bacterial binding and to interactions that might explain the increased binding to RSV-infected cells.
Patients (454) referred for gastroscopy to the General Hospital of Athens were examined to determine (1) if non-secretors were over-represented among patients with ulcers and (2) is there was an association with ABO blood group or secretor status and carriage of Helicobacter pylori.
Compared with the local population, among patients with either gastric ulcer (51) or duodenal ulcer (96) there was a significant increase in the proportion of those who were blood group O (P < 0·025); however, there were no significant differences in the proportions of non-secretors. H. pylori was identified in 62 % of the 454 patients: 59·5 % of those without evidence of ulcers; 62·5 % of those with gastric ulcer; 88% of those with duodenal ulcer (P < 0·0005). These bacteria were cultured more often and in higher numbers from patients with duodenal ulcer (P < 0·025). There was no association between ABO blood group and prevalence of H. pylori. The prevalence of H. pylori among non-secretors with gastric ulcer (12·5%) was significantly lower than that for non-secretors with duodenal ulcer (100%) (P < 0·0005). This was not observed for secretors.
Usage of antibiotics in southern Europe is less well regulated than in northern countries. The proportion (48%) of meningococci in Spain insensitive to penicillin (MIC ≥ 0·1 mg/l) prompted this investigation of antibiotic sensitivities of isolates from Greek patients with meningitis (31) and carriers (47 school-children and 472 recruits). The agar dilution method was used to determine MIC to penicillin G (PN), sulphamethoxazole (SU), rifampicin (RF), cefaclor (CF) and ciprofloxacin (CP).
The proportion of isolates insensitive to PN was 48% for isolates from patients, 19% from school-children and 36·6% from recruits. Resistance to SU (MIC ≥ 16 mg/l) was found in 16% of those from patients, 10·6% from children and 40% from recruits. None of the isolates from patients was resistant to RF (≥ 1 mg/l) but 6% of those from carriers were. Resistance to CF (≥ 4 mg/l) was found in 9·2% of patient isolates, 6·4% from children and 23·7% from recruits. All isolates except one were sensitive to CP (MIC range < 0·0015–0·125 mg/l).
Resistances to PN, SU and RF were analysed by serogroup, serotype and subtype of the bacteria. The proportion of resistant isolates showed some variation between different areas of Greece, but it was not statistically significant.
Non-secretors of ABO blood group antigens are over-represented among patients with meningococcal diseases. Lower levels of secretory IgA reported for non-secretors have been suggested to compromise mucosal defences. Total serum and salivary IgG, IgA and IgM and levels of these isotypes specific for Neisseria lactamica and five isolates of meningococci were determined by ELISA for 357 pupils and staff of a secondary school in which an outbreak of meningitis occurred. There were no differences in total or specific levels of serum IgG, IgA or IgM or salivary IgG or IgA of secretors compared with non-secretors. Non-secretors had significantly lower levels of salivary IgM (P=0·022) A similar pattern was observed for levels of IgM specific for N. lactamica and five meningococcal isolates. The significance of these results is discussed with reference to the role of secretory IgM in protection of mucosal surfaces in infants.
A total of 439 individuals with diabetes mellitus were examined for carriage of yeasts by the oral rinse and palatal swab techniques. Eighteen genetic or environment variables were assessed for their contribution to carriage of yeasts. The factor contributing to palatal and oral carriage of yeasts among individuals with insulin dependent diabetes mellitus (IDDM) was age (P < 0·01). The factor contributing to palatal carriage of yeasts among individuals with non-insulin dependent diabetes mellitus (NIDDM) was poor glycaemic control (glycosuria P < 0·01); carriage in the oral cavity as a whole was influenced additionally by non-secretion of ABH blood group antigens (P < 0·05). Introduction of a denture altered the above risk factors. For individuals with IDDM, oral carriage was associated with the presence of retinopathy (P < 0·05); palatal carriage was influenced by poor glycaemic control (HbA1P < 0·01, plasma glucose levels P < 0·05) and age (P < 0·05). For those with NIDDM, palatal carriage was associated with continuous presence of the denture in the mouth (P < 0·01); oral carriage was associated with plasma glucose levels (P < 0·05).
A survey of ABO blood groups, secretor status and smoking habits among 389 students and staff of a school in which there was an outbreak of meningococcal disease found no difference in the distribution of the ABO blood groups but a significantly higher proportion of non-secretors (37·6%) in the population examined compared with that reported for previous surveys of the neighbouring population in Glasgow (26·2%) (P < 0·0005). There was also a significantly higher proportion of non-secretors among carriers of meningococci (47%) compared with non-carriers (32%). Increased carriage of meningococci among non-secretors might contribute to the increased susceptibility of individuals with this genetic characteristic to meningococcal disease observed in previous studies. Although passive exposure to cigarette smoke has been associated with meningococcal disease, there was no association between passive smoking and carriage. There was, however, a significant association between active smoking and carriage.
The genetically determined inability to secrete the water-soluble glycoprotein form of the ABO blood group antigens into saliva and other body fluids is a recognized risk factor for meningococcal disease. During a community-wide investigation of a prolonged outbreak of disease due to a B15: P1.16 sulphonamideresistant strain of Neisseria meningitidis in Stonehouse, Gloucestershire (the Stonehouse survey), the ABO blood group and secretor status of almost 5000 residents was determined.
The proportion of non-secretors in the Stonehouse population was significantly higher than the proportion of non-secretors among blood donors in the South West Region and in England generally. Seven of 13 Stonehouse residents with meningococcal disease who were tested were found to be non-secretors, a high proportion. The outbreak in Stonehouse cannot be explained solely in terms of the increased proportion of non-secretors. There was no clear correlation between the proportions of non-secretors in different areas within the town and the incidence of cases of meningococcal disease.
Carriers of meningococci, whether outbreak or other strains, were not more likely to be non-secretors. The reasons why non-secretors are more susceptible to meningococcal disease remain to be determined, but they do not appear to be related to carriage of meningococci.
Greek military recruits (993) were examined for carriage of meningococci during July 1990. Blood, saliva and throat swab specimens were obtained and each recruit answered a questionnaire providing information on age, education (a measure of socioeconomic level), place of residence, smoking habits and recent infections.
The overall carriage rate was 25% but differed between the two camps: 79/432 (18%) in Camp A and 168/561 (30%) in Camp B (P < 0·0005). In Camp B, there were significantly higher proportions of recruits who were non-secretors (P < 0·0005), and/or heavy smokers (P < 0·0005). They were also younger ( < 19 years old) (P < 0·001), and on the whole had fewer years of education (P < 0·0005). By univariate analysis, carriage was significantly associated with smoking. By multiple logistic regression analysis, carriage was associated with smoking (P < 0·001), age (P < 0·01) and the camp in which the recruits were based (P < 0·01). Among recruits in Camp B, 15/38 (40%) of those with recent viral infections were carriers compared with 30% for the camp in general.
Non-diabetic individuals who are non-secretors of blood group antigens are prone to superficial infections by Candida albicans. In this study, 216 patients with diabetes mellitus who were denture wearers were examined for the presence or absence of denture stomatitis. There was an overall trend for non-secretors to be prone to denture stomatitis compared with secretors. Stepwise linear discriminant analysis was used to dissect the contribution of secretor status and other variables to the development of the disease. Secretor status was found to be a contributory factor among patients with non-insulin dependent diabetes but not among those with insulin-dependent diabetes. The possible reasons for this are discussed.
Toxigenic strains of Staphylococcus aureus have been suggested to play a role in sudden infant death syndrome (SIDS). In this study we examined two factors that might enhance binding of toxigenic staphylococci to epithelial cells of infants in the age range in which cot deaths are prevalent: expression of the Lewisa antigen and infection with respiratory syncytial virus (RSV). By flow cytometry we demonstrated that binding of three toxigenic strains of S. aureus to cells from non-secretors was significantly greater than to cells of secretors. Pre-treatment of epithelial cells with monoclonal anti-Lewisa or anti-type-1 precursor significantly reduced bacterial binding (P < 0·01); however, attachment of the bacteria correlated only with the amount of Lewisa antigen detected on the cells (P < 0·01). HEp-2 cells infected with RSV bound significantly more bacteria than uninfected cells. These findings are discussed in context of factors previously associated with SIDS (mother's smoking, bottle feeding and the prone sleeping position) and a hypothesis proposed to explain some cases of SIDS.
The white-beaked dolphin (Lagenorhynchus albirostris) and short-beaked common dolphin (Delphinus delphis) are two of the most abundant delphinid species in shelf waters around the United Kingdom (UK) and Republic of Ireland (ROI) in the summer season (May–October). As these two species have similar habitat preferences and diets, it might be expected that they would partition their otherwise shared niche to reduce the potential for competition at this time of year. This study used 569 sightings of the two species, collected from shelf waters (<200 m water depth) in the summer season between 1983 and 1998, to investigate whether there is evidence of widespread niche partitioning based on water temperature in this area. Below 13°C, white-beaked dolphins were dominant with 96% of sightings comprising this species. In contrast, above 14°C, 86% of sightings comprised common dolphins. A classification tree analysis found that of the four eco-geographical variables analysed (water depth, seabed slope, seabed aspect and sea surface temperature), temperature was the most important variable for separating the occurrence of the two species. These results are consistent with widespread temperature-based niche partitioning between white-beaked and common dolphins in shelf waters around the UK and ROI. As temperature is important in determining the relative distribution of these species, the range of the white-beaked dolphin might be expected to contract in response to increasing sea temperature resulting from global climate change, while that of the common dolphin may expand.
Eighteen children with specific language impairment (SLI), from 6 to 8 years of age, were
compared with 9 control children matched on age and nonverbal ability (CA controls) and with 9
younger control children of comparable language level (LA controls). Half of the SLI group were
rated on a teacher checklist as having pragmatic difficulties: these were referred to as the
pragmatic language impairment (PLI) group; the remainder were the typical (SLI-T) group.
Children's responses to adult soliciting utterances were compared. All children usually
responded to conversational solicitations, but children in the PLI group were more likely than
control children to give no response, and they also made very little use of nonverbal responses,
such as nodding. Nonverbal responding was closely related to the quality of children's
responses. Children who failed to use nonverbal responses also had a relatively high level of
pragmatically inappropriate responses that were not readily accounted for in terms of limited
grammar or vocabulary. This study lends support to the notion that there is a subset of the
language-impaired population who have broader communicative impairments, extending beyond
basic difficulties in mastering language form, reflecting difficulty in responding to and
expressing communicative intents. The analytic methods developed for this project have promise
for the study of pragmatic difficulties in other clinical groups.
An understanding of dielectric breakdown mechanisms is critical for continued oxide scaling. Although working transistors have been demonstrated with sub-2nm SiO2 gate dielectrics, the manufacturability of such devices hinges on the reliability of the oxide. As oxides become thinner and operating voltages become lower, a fundamentally different mode of dielectric breakdown occurs. This has been called soft breakdown and is considered to be the formation of a small, localized tunneling path through a dielectric. For transistors with 2-nm gate oxides, threshold voltage and maximum transconductance are not affected by soft breakdown, implying that circuits may continue to operate after soft breakdown. The increase in gate current or voltage noise associated with soft breakdown is not a limiting factor for many applications. However, some cases will be shown in which soft breakdown does degrade device function.
In order to make comparisons of ultra-thin oxide quality, it is important to be able to reliably detect soft breakdown. J-ramp, a commonly used ramped-current measurement to determine oxide quality, is unable to detect soft breakdown in ultra-thin oxides. We will demonstrate the incorporation of noise measurements in a commercial J-ramp algorithm.
It is well established that syntactic form and communicative function do not always correspond: for instance, a syntactic question might function as a request for information (“did you see the play?”) or a request for acknowledgment when there is no doubt about polarity of the response (“there's a tower at Blackpool, isn't there”). Using data from a corpus of 18 child–adult conversations, we distinguished adult utterances that solicited information from those soliciting acknowledgment (i.e., where the response was predictable, and the utterance served a predominantly social function). Both types of utterance were usually responded to by children, but the form of response differed according to the communicative function of the utterance. Nonverbal and prosodic responses (e.g., nods or “mmh”) were significantly more likely to occur in response to utterances soliciting acknowledgment than in response to yes/no questions that solicited information. There were consistent form–function relationships for responses as well as for soliciting utterances. Nonverbal nods and headshakes were not functionally equivalent to verbal “yes” and “no.”
We have observed fluctuations in the tunneling current through 3.5 nm gate oxides with a 1/f power spectrum where f is the frequency. For voltages in the direct tunneling regime we lind an anomalous current dependence of the noise relative to previous observations of noise in thin oxides. We present a simplified model for the current noise in terms of fluctuations in a trap assisted tunneling current that exists in the oxide in addition to the direct tunneling current. Current noise appears to be a very sensitive probe of trap assisted tunneling and degradation in oxides.