From smartphone to bed-side: exploring the use of social media to disseminate recommendations from the National Tracheostomy Safety Project to front-line clinical staff.

Traditional methods used to disseminate educational resources to front-line healthcare staff have several limitations. Social media may increase the visibility of these resources among targeted groups and communities. Our project aimed to disseminate key clinical messages from the National Tracheostomy Safety Project to those caring for patients with tracheostomies or laryngectomies. We commissioned an external media company to design educational material and devise a marketing strategy. We developed videos to communicate recommendations from the safety project and used Facebook, Twitter, YouTube and LinkedIn to deliver these to our target users. We recorded 629,270 impressions over a paid 12-week campaign. Our YouTube channel registered more than a five-fold increase in views and watch time during the campaign as compared with the previous year. Around two-thirds of views across all platforms were from peer-to-peer sharing. We spent £4140 on social media advertising, with each view and click costing £0.02 and £0.67, respectively. This intelligence-led approach using social media is an effective and efficient method to disseminate knowledge on the principles of safe tracheostomy care to front-line clinical staff. Similar strategies may be effective for other patient safety topics, especially when targeting groups that do not use medical journals or other traditional means of dissemination.

Development of highly efficient NEG pumping system for EBIS.

Ultrahigh vacuum inside the ion trap volume is crucial for stable and reliable operation of an Electron Beam Ion Source (EBIS). We have developed and tested a compact linear pumping system based on the ZAO Non-Evaporable Getter (NEG) module with high pumping speed and enhanced sorption capacity for all active gases. Due to its minimal transverse dimensions, the system can be mounted adjacent to the ion trap inside a superconducting solenoid bore and will provide a pumping speed of the order of 1000 l/s for all active gases in that area. An externally supplied current (100 A DC) is used to heat the ZAO NEG up to 650 °C for more than 1 h, which is required for pump activation and/or reactivation cycles. The pumping system is being developed for use in the Extended EBIS Upgrade which is presently in progress at BNL. The design of the system and results of multiple tests are presented and discussed.

Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID.

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8696 controls identified a significant enrichment of DYRK1A truncating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 × 10(-10)) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n=5) and recontacted (n=3) cases with previous case reports, including larger CNV and translocation events (n=7), identified a syndromal disorder among the 15 patients. It was characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models.

DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers.

Chromosomal translocation is the best-characterized genetic mechanism for oncogene activation. However, there are documented examples of activation by alternate mechanisms, for example gene dosage increase, though its prevalence is unclear. Here, we answered the fundamental question of the contribution of DNA amplification as a molecular mechanism driving oncogenesis. Comparing 104 cancer lines representing diverse tissue origins identified genes residing in amplification 'hotspots' and discovered an unexpected frequency of genes activated by this mechanism. The 3431 amplicons identified represent approximately 10 per hematological and approximately 36 per epithelial cancer genome. Many recurrently amplified oncogenes were previously known to be activated only by disease-specific translocations. The 135 hotspots identified contain 538 unique genes and are enriched for proliferation, apoptosis and linage-dependency genes, reflecting functions advantageous to tumor growth. Integrating gene dosage with expression data validated the downstream impact of the novel amplification events in both cell lines and clinical samples. For example, multiple downstream components of the EGFR-family-signaling pathway, including CDK5, AKT1 and SHC1, are overexpressed as a direct result of gene amplification in lung cancer. Our findings suggest that amplification is far more common a mechanism of oncogene activation than previously believed and that specific regions of the genome are hotspots of amplification.

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtype-specific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers.

Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells.

Genetic alterations occurring on human chromosome arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial chromosome clones spanning the 120 megabase (Mb) 1p arm from 1p11.2 to p36.33. The 1p arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580 kb region at 1p34.2-p34.3 and a 270 kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase-polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.

trans-4-[(4-dimethylaminophenyl)-iminomethyl]-N-methyllpyridinium para-toluenesulfonate.

In the title compound, C15H18N3+*C7H7O3S-, the phenylene and pyridyl rings are somewhat twisted with respect to each other, forming a dihedral angle of 23.49 (6) degrees. The compound contains a dipolar chromophoric cation, but crystallizes in the centrosymmetric space group P2(1)/n and is thus not expected to display quadratic non-linear optical effects.

A comparison of the pentaammine(pyridyl)ruthenium(II) and 4-(dimethylamino)phenyl groups as electron donors for quadratic non-linear optics.

Hyper-Rayleigh scattering and Stark spectroscopic studies show that the complex salts [1-4]PF6 have larger static first hyperpolarizabilities beta 0 than [5-8]PF6, because the higher HOMO energy of a (RuII(NH3)5)2+ centre more than offsets the superior pi-orbital overlap in the purely organic chromophores.

Analysis of body composition changes of swine during growth and development.

This study was conducted to model the growth of carcass, viscera, and empty body components and component composition of pigs. Quantitative tissue and chemical composition of 319 swine, representative of barrows and gilts from five commercial genetic populations, was determined at eight stages of growth between 25 and 152 kg. After whole body grinding and carcass dissection, proximate analyses were performed to calculate concentrations of protein, lipid, moisture, and ash of carcass, viscera, empty body, carcass lean, and carcass fat. Linear and nonlinear equations were developed to investigate the growth patterns of each component. Nonlinear growth functions accounted for the greatest amount of variation in empty body protein, lipid, moisture, and ash mass. Differences (P < .05) existed between barrows and gilts for nearly all components investigated. Carcass lean and fat tissues significantly increased in lipid percentage and decreased in moisture percentage as live weight increased. There were significant changes in the ratio and composition of the tissues of barrows and gilts during growth. Nonlinear models fitted the data better than allometric equations for nearly all of the components investigated.

Relationship between endogenous estradiol-17 beta and estrous behavior in heifers.

Thirty-five Holstein heifers were used to examine the relationship between endogenous estradiol-17 beta and estrous traits. During a non-superovulation period (NSP), estrous cycles were synchronized and during the periovulatory stage blood samples were collected every 6 h for 120 h for subsequent determination of estradiol-17 beta and progesterone. In addition, continuous observation for estrous behavior was performed for 98 h. A gonadotropin-induced superovulation period (SP) was begun 12 d after estrus was detected during NSP. Heifers were injected with FSH twice daily for 4 d and single injections of prostaglandin were given on d 14 and 15. Beginning at d 14, blood samples were collected every 6 h for 120 h for subsequent determination of estradiol-17 beta and progesterone. Continuous observation for estrous behavior was performed for 98 h. Peak estradiol-17 beta was greater during SP than during NSP (49.0 +/- 3.1 vs 12.9 +/- 3.0 pg/ml serum). Thirty-three and 31 of the 35 heifers were in estrus during NSP and SP, respectively; duration of estrus was 2.3 h longer during SP than during NSP. However, number of behavioral interactions during estrus did not differ between NSP and SP. In conclusion, estrous traits were similar, whereas peak estradiol-17 beta concentrations were markedly different between NSP and SP.

Evidence for in vivo upregulation of the intestinal vitamin D receptor during dietary calcium restriction in the rat.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] increases intestinal calcium absorption through events that include binding of 1,25(OH)2D3 to the intracellular vitamin D receptor. In vitro studies using mammalian cell cultures reveal an increase in vitamin D receptor content after exposure to 1,25(OH)2D3. To test the hypothesis that 1,25(OH)2D3 increases enterocyte vitamin D receptor content in vivo, male rats were fed either a normal calcium diet (NCD, 1.2% Ca) or low calcium diet (LCD, 0.002% Ca). After 21 d LCD increased serum 1,25(OH)2D3 levels (27 +/- 3 vs. 181 +/- 17 pg/ml, P less than 0.001) and increased transepithelial mucosal to serosal calcium fluxes (Jms) across duodenum (65 +/- 21 vs. 204 +/- 47 nmol/cm2.h, NCD vs. LCD, P less than 0.01) and jejunum (23 +/- 3 vs. 46 +/- 4, P less than 0.007). No change in serosal to mucosal calcium fluxes (Jsm) were observed. LCD increased 1,25(OH)2D3 receptor number threefold in duodenum (32.9 +/- 6.7 vs. 98.7 +/- 13.7 fmol 1,25(OH)2D3/mg protein) and jejunum (34.1 +/- 9.5 vs. 84.9 +/- 7.7) without a change in the receptor affinity for 1,25(OH)2D3 (Kd is 0.17 +/- 0.06 vs. 0.21 +/- 0.02 nM for NCD and LCD duodenum, respectively). Duodenal polyadenylated vitamin D receptor mRNA determined by Northern blot analysis did not increase appreciably during LCD, suggesting that upregulation in vivo may not be due primarily to increased receptor synthesis. The results of this study indicate that under physiologic conditions as during chronic dietary calcium restriction, increased intestinal vitamin D receptor content accompanies increased calcium active transport. Upregulation of the vitamin D receptor by 1,25(OH)2D3 may result primarily from posttranslational processes that decrease degradation of the receptor with increased receptor synthesis responsible for a negligible portion of the accumulation.

Typographic coding in lists and bibliographies.

A comparison was made of the effectiveness of ten systems of typographical/spatial coding suitable for use in the presentation of highly structured information such as bibliographic material. With one exception, which requires a bold typeface, the systems tested are all suitable for the preparation of copy on a standard typewriter or an upper and lowercase line printer. Sections of alphabetical author index were typed in each of the ten styles and subjects were asked to look up lists of entries in each style. The most effective system on balance was a two-unit left extension of the first line of each entry.

The out-of-wedlock pregnancy. Six-years' experience with a university population.

PIP: Illegitimate births are increasing. Associated with this increase are higher rates of prenatal deaths and prematurity, in some studies double that of legitamate births. Marriage after such conception has a higher divorce rate. The present study includes data on every pregnancy diagnosed at the University of California Santa Barbara Student Health Service during 1965-1971. It considers the outcome of those pregnancies and reviews some programs that were instituted with an aim toward prevention. Out-of-wedlock pregnancies decreased after an educational, counseling, and contraception program was instituted. The rate of abortions remained unchanged in spite of liberalized abortion laws; there were no repeaters after the program was instituted. Experience in counseling confirms the contention of several authors that some out-of-wedlock pregnancies stem from subconscious reasons. A multiple disciplinary approach to such pregnancies is advocated.^ieng