Mandibular fractures - what a difference 30 years has made.

This single-centre retrospective study aimed to characterise the epidemiology, management, and outcomes of mandibular trauma presenting to the same tertiary trauma centre 30 years apart, including key paradigm shifts in management and techniques. A total of 393 patients presenting with 665 mandibular fractures were managed by the Oral and Maxillofacial Surgery department at The Royal Melbourne Hospital (RMH), Australia, between 2011 and 2016. Data from a previous RMH paper of 205 patients presenting with 376 mandibular fractures between January 1985 and April 1990 were compared. Results showed an increase in presentations (205 to 393 patients) with an increase in the incidence of mandibular trauma (p = 0.0001), females (12% to 14%), and mean age (29 to 31.1) years. Young males remained the dominant cohort (86%) and interpersonal violence (IPV) the most common aetiology (46% to 43%). Mandibular fractures remained commonly associated with other systemic injuries (49% to 42%), occurring most frequently on the left (49%), and at the angle (29.8%), with most occurring at two sites (53%). Significant paradigm shifts in the management of mandibular trauma saw a reduced need for intermaxillary fixation (76% to 30%, p = 0.0001), increased use of extraoral approaches to the fracture, and the use of semi-rigid internal fixation along ideal lines of osteosynthesis (29% to 87%, p = 0.0001). This demonstrated decreased complications including malocclusion, non-union and delayed union, and permanent nerve injury. There was no significant change in infection, dehiscence rates, and temporary nerve damage.

A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2.

The most common congenital disorder of glycosylation (CDG), phosphomannomutase 2 (PMM2)-CDG, is caused by mutations in PMM2 that limit availability of mannose precursors required for protein N-glycosylation. The disorder has no therapy and there are no models to test new treatments. We generated compound heterozygous mice with the R137H and F115L mutations in Pmm2 that correspond to the most prevalent alleles found in patients with PMM2-CDG. Many Pmm2R137H/F115L mice died prenatally, while survivors had significantly stunted growth. These animals and cells derived from them showed protein glycosylation deficiencies similar to those found in patients with PMM2-CDG. Growth-related glycoproteins insulin-like growth factor (IGF) 1, IGF binding protein-3 and acid-labile subunit, along with antithrombin III, were all deficient in Pmm2R137H/F115L mice, but their levels in heterozygous mice were comparable to wild-type (WT) littermates. These imbalances, resulting from defective glycosylation, are likely the cause of the stunted growth seen both in our model and in PMM2-CDG patients. Both Pmm2R137H/F115L mouse and PMM2-CDG patient-derived fibroblasts displayed reductions in PMM activity, guanosine diphosphate mannose, lipid-linked oligosaccharide precursor and total cellular protein glycosylation, along with hypoglycosylation of a new endogenous biomarker, glycoprotein 130 (gp130). Over-expression of WT-PMM2 in patient-derived fibroblasts rescued all these defects, showing that restoration of mutant PMM2 activity is a viable therapeutic strategy. This functional mouse model of PMM2-CDG, in vitro assays and identification of the novel gp130 biomarker all shed light on the human disease, and moreover, provide the essential tools to test potential therapeutics for this untreatable disease.

MS in the analysis of biosimilars.

Biologic drugs are forming a larger and expanded part of the therapeutic drug market. The top ten best-selling drugs are currently a mix of small and large molecules, but it is expected that biologics will soon represent a large majority of the top-selling drugs. These drugs have a high degree of complexity and must be analyzed using information-rich analytical techniques to fully characterize the drug. Thus, biosimilar copies of these innovator drugs must also be intensively analyzed to ensure they have comparable analytical profiles. In this article we discuss the regulatory requirements for introducing a follow-on biologic, or biosimilar, drug on the market, how analytics in general can be used to reduce the need for comprehensive clinical trials, and how MS in particular is becoming increasingly valuable in these analyses.

Do weak phonological representations impact on arithmetic development? A review of research into arithmetic and dyslexia.

We review significant empirical studies of the arithmetic abilities of children with dyslexia. These studies suggest that the academic impairments of children with dyslexia are not limited to reading and spelling, but also include aspects of mathematics. A consistent finding across a number of studies is that children with dyslexia have difficulty recalling number facts. The results of the reviewed studies are analysed, both in terms of the weak phonological representations hypothesis, and the triple-code theory of mathematical cognition. It is suggested that the phonological processing deficits of individuals with dyslexia impair aspects of mathematics that rely on the manipulation of verbal codes (e.g. counting speed, number fact recall), whilst other aspects of mathematics that are less reliant on verbal codes (e.g. estimation, subitising) are unimpaired. Suggestions for testing this hypothesis are put forward.

Computerized screening for visual stress in children with dyslexia.

Visual stress-a condition in which unpleasant visual symptoms are experienced when reading-has been reported to be more prevalent in dyslexic individuals but at the present time the relationship between dyslexia and visual stress remains controversial. ViSS, a computerized visual stress screener that incorporates reading-like visual search, has recently shown promise in studies with unselected samples of primary and secondary school children. This study investigated the use of ViSS with dyslexic children. Dyslexic children identified as having high visual stress showed significantly higher per cent increases in reading rate with a coloured overlay and reported significantly higher critical symptoms of visual stress, compared to dyslexic children with low visual stress. The same results were found for reading-age controls, indicating that ViSS can be equally effective with normal readers as well as with children with dyslexia. Compared to reading-age controls, dyslexic children were found to have significantly higher susceptibility to visual stress, significantly larger per cent increases in reading rate with an overlay, and significantly higher critical and non-critical symptoms of visual stress. Extrapolated to unselected population samples, the data also suggest that visual stress is more likely to be found in people with dyslexia than in people who do not have dyslexia. These results, which point to an important link between the two conditions, are discussed in relation to current theories that attribute visual stress to either a magnocellular dysfunction or cortical hyperexcitability.

Discovery of chemical reactions through multidimensional screening.

Multidimensional reaction screening of ortho-alkynyl benzaldehydes with a variety of catalysts and reaction partners was conducted in an effort to identify new chemical reactions. Reactions affording unique products were selected for investigation of preliminary scope and limitations.

The mental and written arithmetic abilities of adults with dyslexia.

The abilities of 19 adult students with dyslexia and 19 students without dyslexia to recall number facts were compared. Despite being matched for estimated IQ, the dyslexic students were less accurate than the non-dyslexic students when answering subtraction and multiplication questions. When the dyslexic students answered addition and subtraction questions correctly they did so more slowly than the non-dyslexic students. It was concluded that dyslexic adults have greater difficulty recalling number facts than non-dyslexic adults. No statistically significant correlations were found between the dyslexic students' performance on the tests of number fact recall and their performance on tests of auditory-verbal and visual-spatial memory.

Measurement mischief: a critique of Reynolds, Nicolson and Hambly (2003).

Reynolds, Nicolson and Hambly (2003) report an intervention study of the effects of exercise-based training on literacy development, using literacy measures from the Dyslexia Screening Test (DST), the NFER-Nelson Group Reading Test, and the Standard Assessment Tasks (SATs). Investigation of the nature and psychometric characteristics of these measures casts serious doubt on their appropriateness in a study of this nature. Consideration of the findings obtained using these measures does not support the authors' conclusion that reading was improved by the intervention. The study by Reynolds et al. does not demonstrate that exercise-based treatment improves literacy skills and the use of its purported findings as evidence that exercise-based treatment would be beneficial for children with literacy difficulties is scientifically untenable.