Genomewide profiling of copy‐number alteration in monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy‐number alterations (CNAs) in 90 MGUS and 33 MM patients using high‐density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10^?5) and showed median number of CNAs is lower in MGUS (3, range 0–22) than in MM (13, range 4–38, P = 1.82 × 10^?10). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.     

Role of insulin resistance indices in predicting new‐onset diabetes after kidney transplantation

New‐onset diabetes mellitus (NODAT) is a serious complication following renal transplantation. In this cohort study, we studied 118 nondiabetic renal transplant recipients to examine whether indices of insulin resistance and secretion calculated before transplantation and at 3 months post‐transplantation are associated with the development of NODAT within 1 year. We also analysed the long‐term impact of early diagnosed NODAT. Insulin indices were calculated using homeostasis model assessment (HOMA) and McAuley's Index. NODAT was diagnosed using fasting plasma glucose. Median follow‐up was 11 years. The cumulative incidence of NODAT at 1 year was 37%. By logistic regression, recipient age (per year) was the only significant pretransplant predictor of NODAT (OR 1.04, CI 1.009–1.072), while age (OR 1.04, CI 1.005–1.084) and impaired fasting glucose (OR 2.97, CI 1.009–8.733) were significant predictors at 3 months. Pretransplant and 3‐month insulin resistance and secretion indices did not predict NODAT. All‐cause mortality was significantly higher in recipients developing NODAT within 1 year compared with those remaining nondiabetic (44% vs. 22%, log‐rank P = 0.008). By Cox's regression analysis, age (HR 1.075, CI 1.042–1.110), 1‐year creatinine (HR 1.007, CI 1.004–1.010) and NODAT within 3 months (HR 2.4, CI 1.2–4.9) were independent predictors of death. In conclusion, NODAT developing early after renal transplantation was associated with poor long‐term patient survival. Insulin indices calculated pretransplantation using HOMA and McAuley's Index did not predict NODAT.     

Herd immunity effect of the HPV vaccination program in Australia under different assumptions regarding natural immunity against re-infection

Deterministic dynamic compartmental transmission models (DDCTMs) of human papillomavirus (HPV) transmission have been used in a number of studies to estimate the potential impact of HPV vaccination programs. In most cases, the models were built under the assumption that an individual who cleared HPV infection develops (life-long) natural immunity against re-infection with the same HPV type (this is known as SIR scenario). This assumption was also made by two Australian modelling studies evaluating the impact of the National HPV Vaccination Program to assist in the health-economic assessment of male vaccination. An alternative view denying natural immunity after clearance (SIS scenario) was only presented in one study, although neither scenario has been supported by strong evidence. Some recent findings, however, provide arguments in favour of SIS.     

Involved surgical margins in oral and oropharyngeal carcinoma—an anatomical problem?

A previous audit conducted in the West of Scotland (WoS) suggested that anatomical factors accounted for a substantial proportion of invaded surgical margins after resection of an oral or oropharyngeal squamous cell carcinoma (SCC). Since then a number of technical improvements have taken place, the most important of which has been advanced digital imaging that has enabled better surgical planning. In this study we compare the incidence of involved surgical margins in a recent group with those found in the earlier audit. The earlier (WoS) group comprised a consecutive series of patient operated on for a primary SCC of the oral cavity or oropharynx between November 1999 and November 2001 (n = 296). The later series comprised 178 patients operated on for oral or oropharyngeal SCC at the Southern General Hospital (SGH), Glasgow, between 2006 and 2009. A total of 245 patients in the WoS cohort had information available on the invasion of the margins of whom 68 (28%) had an invaded margin. Of 177 patients in the SGH group, 9 (5%) had an invaded margin (p = 0.001). An anatomical approach to the resection of oral and oropharyngeal SCC is appropriate, as it results in a rate of invaded margins of less than 10% irrespective of size and site of the primary lesion.     

Knots and nonorientable surfaces in chiral nematics

Knots and knotted fields enrich physical phenomena ranging from DNA and molecular chemistry to the vortices of fluid flows and textures of ordered media. Liquid crystals provide an ideal setting for exploring such topological phenomena through control of their characteristic defects. The use of colloids in generating defects and knotted configurations in liquid crystals has been demonstrated for spherical and toroidal particles and shows promise for the development of novel photonic devices. Extending this existing work, we describe the full topological implications of colloids representing nonorientable surfaces and use it to construct torus knots and links of type (p,2) around multiply twisted Möbius strips.