Involvement of Cyclin-Dependent Kinase-Like 2 in Cognitive Function Required for Contextual and Spatial Learning in Mice

Cyclin-dependent kinase-like 2 (Cdkl2) is a cdc2-related serine/threonine protein kinase that is postnatally expressed in various brain regions, including the cerebral cortex, entorhinal cortex, hippocampus, amygdala, and dorsal thalamus. The extremely high Cdkl2 expression in these regions suggests that it has a role in cognition and emotion. Recent genetic studies indicate that mutations of Cdkl family kinases are associated with neurodevelopmental and neuropsychiatric disorders in humans. To elucidate the physiologic role of Cdkl2, we behaviorally analyzed Cdkl2LacZ/LacZ mice lacking Cdkl2. Cdkl2LacZ/LacZ mice had reduced latencies to enter the dark compartment after electric footshock in an inhibitory avoidance task and attenuated contextual fear responses when exposed to mild training conditions. Hippocampal spatial learning in the Morris water maze was slightly anomalous with mice exhibiting an abnormal swimming pattern. The aversive response in a two-way avoidance task was slightly, but not significantly, enhanced. On the other hand, Cdkl2LacZ/LacZ mice did not exhibit altered sensitivity to aversive stimuli, such as electric footshock and heat, or deficits in the elevated plus maze or rotating rod test. These findings suggest that Cdkl2 is involved in cognitive function and provide in vivo evidence for the function of Cdkl family kinases expressed in terminally differentiated neurons in mice

Bulletin No. 17: Preserving Our Freshwater Wetlands

Reprints of a series of articles on why this is important and how it can be done. 52 pp. 1970

Atomic Hydrogen and Star Formation in the Bridge/Ring Interacting Galaxy Pair NGC 7714/7715 (Arp 284)

We present high spatial resolution 21 cm HI maps of the interacting galaxy pair NGC 7714/7715. We detect a massive (2 x 10**9 M(sun)) HI bridge connecting the galaxies that is parallel to but offset from the stellar bridge. A chain of HII regions traces the gaseous bridge, with H-alpha peaks near but not on the HI maxima. An HI tidal tail is also detected to the east of the smaller galaxy NGC 7715, similarly offset from a stellar tail. The strong partial stellar ring on the eastern side of NGC 7714 has no HI counterpart, but on the opposite side of NGC 7714 there is a 10**9 M(sun) HI loop 11 kpc in radius. Within the NGC 7714 disk, clumpy HI gas is observed associated with star formation regions. Redshifted HI absorption is detected towards the starburst nucleus. We compare the observed morphology and gas kinematics with gas dynamical models in which a low-mass companion has an off-center prograde collision with the outer disk of a larger galaxy. These simulations suggest that the bridge in NGC 7714/7715 is a hybrid between bridges seen in systems like M51 and the purely gaseous `splash' bridges found in ring galaxies like the Cartwheel. The offset between the stars and gas in the bridge may be due to dissipative cloud-cloud collisions occuring during the impact of the two gaseous disks.Comment: 31 pages, Latex, 11 figures, to be published in the July 10, 1997 issue of the Astrophysical Journa

The stroke ‘Act FAST’ campaign: Remembered but not understood?

Background: The stroke awareness raising campaign ‘Act FAST' (Face, Arms, Speech: Time to call Emergency Medical Services) has been rolled out in multiple waves in England, but impact on stroke recognition and response remains unclear. Purpose: The purpose of this study was to test whether providing knowledge of the FAST acronym through a standard Act FAST campaign leaflet increases accurate recognition and response in stroke-based scenario measures. Methods: This is a population-based, cross-sectional survey of adults in Newcastle upon Tyne, UK, sampled using the electoral register, with individuals randomized to receive a questionnaire and Act FAST leaflet (n = 2500) or a questionnaire only (n = 2500) in 2012. Campaign message retention, stroke recognition, and response measured through 16 scenario-based vignettes were assessed. Data were analyzed in 2013. Results: Questionnaire return rate was 32·3% (n = 1615). No differences were found between the leaflet and no-leaflet groups in return rate or demographics. Participants who received a leaflet showed better campaign recall (75·7% vs. 68·2%, P = 0·003) and recalled more FAST mnemonic elements (66·1% vs. 45·3% elements named correctly, P < 0·001). However, there were no between-group differences for stroke recognition and response to stroke-based scenarios (P > 0·05). Conclusions: Despite greater levels of recall of specific ‘Act FAST' elements among those receiving the Act FAST leaflet, there was no impact on stroke recognition and response measures

Witness Response at Acute Onset of Stroke: A Qualitative Theory-Guided Study

Background: Delay in calling emergency medical services following stroke limits access to early treatment that can reduce disability. Emergency medical services contact is mostly initiated by stroke witnesses (often relatives), rather than stroke patients. This study explored appraisal and behavioural factors that are potentially important in influencing witness behaviour in response to stroke. Methods and Findings: Semi-structured interviews with 26 stroke witnesses were transcribed and theory-guided content analysed was undertaken based on the Common Sense Self-Regulation Model (appraisal processes) and Theory Domains Framework (behavioural determinants). Response behaviours were often influenced by heuristics-guided appraisal (i.e. mental rules of thumb). Some witnesses described their responses to the situation as ‘automatic' and ‘instinctive', rather than products of deliberation. Potential behavioural influences included: environmental context and resources (e.g. time of day), social influence (e.g. prompts from patients) and beliefs about consequences (e.g. 999 accesses rapid help). Findings are based on retrospective accounts and need further verification in prospective studies. Conclusions: Witnesses play a key role in patient access to emergency medical services. Factors that potentially influence witnesses' responses to stroke were identified and could inform behavioural interventions and future research. Interventions might benefit from linking automatic/instinctive threat perceptions with deliberate appraisal of stroke symptoms, prompting action to call emergency medical services

Comparison of the next-generation Xpert MRSA/SA BC assay and the GeneOhm StaphSR assay to routine culture for identification of Staphylococcus aureus and methicillin-resistant S. aureus in positive-blood-culture broths

A bloodstream infection with Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is a serious condition that carries a high mortality rate and is also associated with significant hospital costs. The rapid and accurate identification and differentiation of methicillin-susceptible S. aureus (MSSA) and MRSA directly from positive blood cultures has demonstrated benefits in both patient outcome and cost-of-care metrics. We compare the next-generation Xpert MRSA/SA BC (Xpert) assay to the GeneOhm StaphSR (GeneOhm) assay for the identification and detection of S. aureus and methicillin resistance in prospectively collected blood culture broths containing Gram-positive cocci. All results were compared to routine bacterial culture as the gold standard. Across 8 collection and test sites, the Xpert assay demonstrated a sensitivity of 99.6% (range, 96.4% to 100%) and a specificity of 99.5% (range, 98.0% to 100%) for identifying S. aureus, as well as a sensitivity of 98.1% (range, 87.5% to 100%) and a specificity of 99.6% (range, 98.3% to 100%) for identifying MRSA. In comparison, the GeneOhm assay demonstrated a sensitivity of 99.2% (range, 95.2% to 100%) and a specificity of 96.5% (range, 89.2% to 100%) for identifying S. aureus, as well as a sensitivity of 94.3% (range, 87.5% to 100%) and a specificity of 97.8% (range, 96.1% to 100%) for identifying MRSA. Five of six cultures falsely reported as negative for MRSA by the GeneOhm assay were correctly identified as positive by the Xpert assay, while one culture falsely reported as negative for MRSA by the Xpert assay was correctly reported as positive by the GeneOhm assay

Research is ‘a step into the unknown’: an exploration of pharmacists’ perceptions of factors impacting on research participation in the NHS

Objective This study explored National Health Service (NHS) pharmacists’ perceptions and experiences of pharmacist-led research in the workplace.  Design Semistructured, face-to-face discussions continued until distinct clusters of opinion characteristics formed. Verbatim transcripts of audio-recordings were subjected to framework analysis.  Setting Interviews were carried out with 54 pharmacists with diverse backgrounds and roles from general practices and secondary care in the UK's largest health authority.  Results The purpose and potential of health services research (HSR) was understood and acknowledged to be worthwhile by participants, but a combination of individual and system-related themes tended to make participation difficult, except when this was part of formal postgraduate education leading to a qualification. Lack of prioritisation was routinely cited as the greatest barrier, with motivation, confidence and competence as additional impediments. System-related themes included lack of practical support and pharmacy professional issues. A minority of highly motivated individuals managed to embed research participation into routine activity.  Conclusions Most pharmacists realised the desirability and necessity of research to underpin pharmacy service expansion, but a combination of individual and professional level changes is needed to increase activity. Our findings provide a starting point for better understanding the mindset of hospital-based and general practice-based pharmacists towards research, as well as their perceived barriers and supports

Most Common Single-Nucleotide Polymorphisms Associated With Rheumatoid Arthritis in Persons of European Ancestry Confer Risk of Rheumatoid Arthritis in African Americans

Objective. Large-scale genetic association studies have identified \u3e20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA risk in an African American population. Methods. Twenty-seven candidate single-nucleotide polymorphisms (SNPs) were genotyped in 556 autoantibody-positive African Americans with RA and 791 healthy African American control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were compared with previously published ORs for RA patients of European ancestry. We then calculated a composite genetic risk score (GRS) for each individual based on the sum of all risk alleles. Results. Overlap of the ORs and 95% CIs between the European and African American populations was observed for 24 of the 27 candidate SNPs. Conversely, 3 of the 27 SNPs (CCR6 rs3093023, TAGAP rs394581, and TNFAIP3 rs6920220) demonstrated ORs in the opposite direction from those reported for RA patients of European ancestry. The GRS analysis indicated a small but highly significant probability that African American patients relative to control subjects were enriched for the risk alleles validated in European RA patients (P = 0.00005). Conclusion. The majority of RA risk alleles previously validated for RA patients of European ancestry showed similar ORs in our population of African Americans with RA. Furthermore, the aggregate GRS supports the hypothesis that these SNPs are risk alleles for RA in the African American population. Future large-scale genetic studies are needed to validate these risk alleles and identify novel RA risk alleles in African Americans

Salvage high-dose chemotherapy in female patients with relapsed/refractory germ-cell tumors: A retrospective analysis of the European Group for Blood and Marrow Transplantation (EBMT)

Background: High-dose chemotherapy (HDC) with hematopoietic progenitor cell transplantation is a standard option for relapsed/refractory testicular germ-cell tumor (GCT), but only few data have been reported in female patients with GCT. We conducted a retrospective analysis of female patients with GCT treated with HDC and registered with the European Society for Blood and Marrow Transplantation. Patients and methods: Between 1985 and 2013, 60 registered female patients with GCT, median age 27 years (range 15-48), were treated with salvage HDC. Forty patients (67%) had primary ovarian GCT, 8 (13%) mediastinal, 7 (12%) retroperitoneal and 5 (8%) other primary sites/unknown. Twenty-two patients (37%) received HDC as second-line therapy, 29 (48%) as third-line, and 9 (15%) as fourth- to sixth-line. Nine of 60 patients (15%) received HDC as late-intensification with no evidence of metastasis before HDC. The conditioning HDC regimens comprised carboplatin in 51 of 60 cases (85%), and consisted of a single HDC cycle in 31 cases (52%), a multi-cycle HDC regimen in 29 (48%). Results: Nine cases who underwent late intensification HDC were not evaluable for response. Of the other 51 assessable patients, 17 (33%) achieved a complete response (CR), 8 (16%) a marker-negative partial remission (PRm-), 5 (10%) a marker-positive partial remission, 5 (10%) stable disease, and 13 (25%) progressive disease. There were 3 toxic deaths (6%). With an overall median follow-up of 14 months (range 1-219), 7 of 9 (78%) patients with late intensification and 18 of the 25 patients (72%) achieving a CR/PRm- following HDC were free of relapse/progression. In total, 25 of 60 patients (42%) were progression-free following HDC at a median follow-up of 87 months (range 3-219 months). Conclusions: Salvage HDC based on carboplatin represents a therapeutic option for female patients with relapsed/refractory GCT