Cinema-going at the Southampton Odeon: Exhibition Data and Popular Taste

Cinemagoing data from the 1970s. A case study of the data from the Southampton Odeon

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2sigma;2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2sigma;2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca<inf>o</inf>²⁺) homeostasis. To elucidate the role of AP2sigma;2 in Ca<inf>o</inf>²⁺ regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2sigma;2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2sigma;2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2sigma;2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2sigma;2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2sigma;2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue.

Prognostic role of lemur tyrosine kinase-3 germline polymorphisms in adjuvant gastric cancer in Japan and the United States

Lemur tyrosine kinase-3 (LMTK3) was recently identified as an estrogen receptor (ER)-α modulator related to endocrine therapy resistance, and its polymorphisms rs9989661 (T>C) T/T genotype and rs8108419 (G>A) G/G or A/G genotype predicted improved outcomes in breast cancer. Because different predominant ER distributions link to breast and gastric cancer and little is known of the prognostic role of LMTK3 in gastric cancer, this study was carried out to clarify the prognostic role of these polymorphisms in gastric cancer. One-hundred and sixty-nine Japanese and 137 U.S. patients with localized gastric adenocarcinoma were enrolled. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA sequencing. Overall, these polymorphisms were not associated with survival in both cohorts. When gender was considered, in multivariate analysis, harboring rs9989661 T/T genotype was associated with disease-free survival [HR, 4.37; 95% confidence interval (CI), 2.08-9.18; P < 0.0001] and overall survival (OS; HR, 3.69; 95% CI, 1.65-8.24; P = 0.0014) in the Japanese males and time to recurrence (HR, 7.29; 95% CI, 1.07-49.80; P = 0.043) in the U.S. females. Meanwhile, harboring rs8108419 G/G genotype was associated with OS in the Japanese females (HR, 3.04; 95% CI, 1.08-8.56; P = 0.035) and the U.S. males (HR, 3.39; 95% CI, 1.31-8.80; P = 0.012). The prognostic role of these polymorphisms may be negative in gastric cancer. These findings suggest that the estrogen pathway may play a prognostic role in patients with gastric cancer but this may be dependent on the regional differences both in physiology and genetic alterations of gastric cancer.

Diagnostic performance on briefly presented digital pathology images

Background: Identifying new and more robust assessments of proficiency/expertise (finding new "biomarkers of expertise") in histopathology is desirable for many reasons. Advances in digital pathology permit new and innovative tests such as flash viewing tests and eye tracking and slide navigation analyses that would not be possible with a traditional microscope. The main purpose of this study was to examine the usefulness of time-restricted testing of expertise in histopathology using digital images.
Methods: 19 novices (undergraduate medical students), 18 intermediates (trainees), and 19 experts (consultants) were invited to give their opinion on 20 general histopathology cases after 1 s and 10 s viewing times. Differences in performance between groups were measured and the internal reliability of the test was calculated.
Results: There were highly significant differences in performance between the groups using the Fisher's least significant difference method for multiple comparisons. Differences between groups were consistently greater in the 10-s than the 1-s test. The Kuder-Richardson 20 internal reliability coefficients were very high for both tests: 0.905 for the 1-s test and 0.926 for the 10-s test. Consultants had levels of diagnostic accuracy of 72% at 1 s and 83% at 10 s.
Conclusions: Time-restricted tests using digital images have the potential to be extremely reliable tests of diagnostic proficiency in histopathology. A 10-s viewing test may be more reliable than a 1-s test. Over-reliance on "at a glance" diagnoses in histopathology is a potential source of medical error due to over-confidence bias and premature closure.

Superimposition: A composition for harp, saxophone and live electronics

Superimposition is built on a live-scoring system. Computer animated graphics combined with computer generated algorithms produce the score in real time based on preferences input by the composer. Notably, this system introduces a methodology for eliciting complex and coordinated rhythms from instrumentalists through notation generated in real time. This work also incorporates a system for live electronics and live sampling and processing.

Petals of Resonance: A performance system for the transformation of small body sounds

A system of software and hardware that combines signal processing and contact microphones using normally inaudible body sounds, including heartbeat/pulse, respiration and internal sounds from the vocal tract that can be heard internally by the performer but not externally by others, to drive resonant filters. Performance at SARC Sonic Lab, Belfast, 19 Feb 2015 in collaboration with Birgit Ulher.

Feedback Networks and Self-Oscillating Objects

A system of self-designed microphones, speakers and transducers creating performable feedback networks and self-oscillating objects. Performance SARC Sonic Lab, Belfast, 18 March 2015

Tools and Environments for Networked Electronic Performance

A collection of software and hardware tools and environments that facilitate collective networked performance between electronic musicians. Tools include 'Chat Monkey', a live chat tool for performance, 'DMA Sequencing', a step sequencer using open sound control messaging and multi nodal control, 'tutti, duet, trio, solo, quartet', an ensemble management environment, and 'Por Larrañaga', a cigar box based electro-acoustic instrument with embedded sensors and controllers. Notable performances: w/BLISS, NCAD, Dublin, 1 March 2015; w/BLISS, NI Science Festival, Belfast, 21 Feb 2015