Protein crystallography with a micrometre-sized synchrotron-radiation beam

For the first time, protein microcrystallography has been performed with a focused synchrotron-radiation beam of 1 µm using a goniometer with a sub-micrometre sphere of confusion. The crystal structure of xylanase II has been determined with a flux density of about 3 × 1010 photons s−1 µm−2 at the sample

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

A candidate gene for congenital bilateral isolated ptosis identified by molecular analysis of a de novo balanced translocation

Ptosis is defined as drooping of the upper eyelid and can impair full visual acuity. It occurs in a number of forms including congenital bilateral isolated ptosis, which may be familial and for which two linkage groups are known on chromosomes 1p32-34.1 and Xq24-27.1. We describe the analysis of the chromosome breakpoints in a patient with congenital bilateral isolated ptosis and a de novo balanced translocation 46,XY,t(1;8)(p34.3;q21.12). Both breakpoints were localized by fluorescence in situ hybridisation with yeast artificial chromosomes, bacterial artificial chromosomes and P1 artificial chromosomes. The derived chromosomes were isolated by flow-sorting, amplified by degenerate oligonucleotide-primed polymerase chain reaction and analyzed by sequence tagged sites amplification to map the breakpoints at a resolution that enabled molecular characterization by DNA sequencing. The 1p breakpoint lies ~13 Mb distal to the previously reported linkage locus at 1p32-1p34.1 and does not disrupt a coding sequence, whereas the chromosome 8 breakpoint disrupts a gene homologous to the mouse zfh-4gene. Murine zfh-4 codes for a zinc finger homeodomain protein and is a transcription factor expressed in both muscle and nerve tissue. Human ZFH-4 is therefore a candidate gene for congenital bilateral isolated ptosis

The Incidence, Pattern, and Prognostic Value of Left Ventricular Myocardial Scar by Late Gadolinium Enhancement in Patients With Atrial Fibrillation

Objectives We aimed to identify the frequency, pattern, and prognostic significance of left ventricular (LV) late gadolinium enhancement (LGE) in patients with atrial fibrillation (AF). Background There are limited data on the presence, pattern, and prognostic significance of LV myocardial fibrosis in patients with AF. Late gadolinium enhancement during cardiac magnetic resonance (CMR) is a marker for myocardial fibrosis. Methods We studied a consecutive group of 664 patients without known prior myocardial infarction being referred for radiofrequency ablation of AF. CMR was requested to assess pulmonary venous anatomy. Results Overall, 73% were male, with an average age of 56 years, and an ejection fraction of 55±10%. Left ventricular LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort we observed 68 deaths over a median follow-up period of 42 months. On univariable analysis, age (HR 1.05, CI 1.03–1.08, LRχ2 15.2, p=0.0001), diabetes (HR 2.39, CI 1.41–4.09, LRχ210.3, p=0.001), a history of heart failure (HR 1.78, CI 1.09–2.91, LRχ2 5.37, p=0.02), left atrial dimension (HR 1.04, CI 1.01–1.08, LRχ2 6.47, p=0.01), presence of LGE (HR 5.08, CI 3.08–8.36, LRχ2 28.8, p<0.0001), and LGE extent (HR 1.15, CI 1.10–1.21, LRχ2 35.6, p<0.0001) provided the strongest association with mortality. The mortality rate was 8.1% per patient-years in patients with LGE vs. 2.3% patients without LGE. In the best overall multivariable model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in LGE associated with a 15% increased risk of death. Conclusions In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality