Open Access and Scholarly Books: Workshop Report, 19 June 2013

On 19 June 2013 Knowledge Unlatched and the Berkman Center for Internet and Society at Harvard Law School jointly convened a one-day workshop titled Open Access and Scholarly Books in Cambridge, MA. The workshop brought together a group of 21 invited publishers, librarians, academics and Open Access innovators to discuss the challenge of making scholarly books Open Access. This report captures discussions that took place on the day.

Association between a 19 bp deletion polymorphism at the dopamine beta-hydroxylase (DBH) locus and migraine with aura

Migraine is a debilitating neurological disorder, affecting 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is unclear. Our previous work has investigated dopamine related migraine candidate genes and has reported a significant allelic association with migraine of a microsatellite localised to the promoter region of the dopamine beta-hydroxylase (DBH) gene. The present study performed an association analysis in a larger population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining two different genetic DBH polymorphisms (a functional insertion/deletion promoter and a coding SNP A444G polymorphism). Although no significant association was found for the SNP polymorphism, the results showed a significant association between the insertion/deletion variant and disease (chi(2)=8.92, P=0.011), in particular in migraine with aura (chi(2)=11.53, P=0.003) compared to the control group. Furthermore, the analysis of this polymorphism stratified by gender, revealed that male individuals with the homozygote deletion genotype had three times the risk of developing migraine, compared to females. The DBH insertion/deletion polymorphism is in linkage disequilibrium with the previously reported migraine associated DBH microsatellite and this insertion/deletion polymorphism is functional, which may explain a potential role in susceptibility to migraine.

Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension

A polymorphism of the angiotensin I converting enzyme (ACE) gene has recently been reported and analysis of this polymorphism has indicated that it is associated with several cardiovascular diseases. However, the results are still controversial and such association has not yet been established conclusively. To determine whether the ACE gene may be responsible for essential hypertension in a Japanese population, we also compared the distribution of genotypes and the allele frequency of this polymorphism in our findings of a Japanese population with these features in other countries. Eighty-seven hypertensive patients with a family history of essential hypertension and 95 normotensive patients whose parents had no such history were enrolled in the study. Polymorphism of the ACE gene was determined by using the polymerase chain reaction. Homozygotes for this polymorphism had either a 490-bp band (II) or a 190-bp band (DD) and heterozygotes had both bands (ID). In hypertensive subjects, the numbers and frequency of the ACE genotypes were: II, 44 (0.51); ID, 26 (0.30); DD, 17 (0.19). In normotensive subjects these were: II, 35 (0.37); ID, 43 (0.45); DD, 17 (0.18). There were no significant differences between the two groups in derived allele frequencies (chi 2 = 1.41). The difference between the overall allelic frequency in Japan and that reported in several other countries was significant. We did not find any association between ACE gene polymorphism and essential hypertension in Japan. However, there were significant differences in derived allele frequencies between our findings in a Japanese population and those reported from Europe and Australia.

Changing parental high risk behaviour in the reduction of SIDS : the imperative of translational research

Objectives To investigate the factors associated with sudden infant death syndrome (SIDS) from birth to age 2 years, whether recent advice has been followed, whether any new risk factors have emerged, and the specific circumstances in which SIDS occurs while cosleeping (infant sharing the same bed or sofa with an adult or child). Design Four year population based case-control study. Parents were interviewed shortly after the death or after the reference sleep (within 24 hours) of the two control groups. Setting South west region of England (population 4.9 million, 184 800 births). Participants 80 SIDS infants and two control groups weighted for age and time of reference sleep: 87 randomly selected controls and 82 controls at high risk of SIDS (young, socially deprived, multiparous mothers who smoked). Results The median age at death (66 days) was more than three weeks less than in a study in the same region a decade earlier. Of the SIDS infants, 54% died while cosleeping compared with 20% among both control groups. Much of this excess may be explained by a significant multivariable interaction between cosleeping and recent parental use of alcohol or drugs (31% v 3% random controls) and the increased proportion of SIDS infants who had coslept on a sofa (17% v 1%). One fifth of SIDS infants used a pillow for the last sleep (21% v 3%) and one quarter were swaddled (24% v 6%). More mothers of SIDS infants than random control infants smoked during pregnancy (60% v 14%), whereas one quarter of the SIDS infants were preterm (26% v 5%) or were in fair or poor health for the last sleep (28% v 6%). All of these differences were significant in the multivariable analysis regardless of which control group was used for comparison. The significance of covering the infant’s head, postnatal exposure to tobacco smoke, dummy use, and sleeping in the side position has diminished although a significant proportion of SIDS infants were still found prone (29% v 10%). Conclusions Many of the SIDS infants had coslept in a hazardous environment. The major influences on risk, regardless of markers for socioeconomic deprivation, are amenable to change and specific advice needs to be given, particularly on use of alcohol or drugs before cosleeping and cosleeping on a sofa.

Visibility-related characteristics of crashes involving bicyclists and motor vehicles – Responses from an online questionnaire study

Bicyclists are among the most vulnerable of road users, with high fatal crash rates. Although visibility aids have been widely advocated to help prevent bicycle-vehicle conflicts, to date no study has investigated, among crash-involved cyclists, the kind of visibility aids they were using at the time of the crash. This study undertook a detailed investigation of visibility factors involved in bicyclist-motor-vehicle crashes. We surveyed 184 bicyclists (predominantly from Australia via internet cycling forums) who had been involved in motor vehicle collisions regarding the perceived cause of the collision, ambient weather and general visibility, as well as the clothing and bicycle lights used by the bicyclist. Over a third of the crashes occurred in low light levels (dawn, dusk or night-time), which is disproportionate given that only a small proportion of bicyclists typically ride at these times. Importantly, 19% of these bicyclists reported not using bicycle lights at the time of the crash, and only 34% were wearing reflective clothing. Only two participants (of 184) nominated bicyclist visibility as the cause of the crash: 61% attributed the crash to driver inattention. These findings demonstrate that crash-involved bicyclists tend to under-rate and under-utilise visibility aids as a means of improving their safety.

Psychological health of medical and dental students in Saudi Arabia : a longitudinal study

Introduction: Many studies have indicated the poor psychological health of medical and dental students. However, few studies have assessed the longitudinal trajectory of that psychological health at different times in an academic year. Aim: To evaluate the positive and negative aspects of psychological health among preclinical medical and dental students in Saudi Arabia prospectively. Methods: A total of 317 preclinical medical and dental students were recruited for a longitudinal study design from second and third-year students at Umm Al-Qura University in the 2012-2013 academic year. The students were assessed at the middle of the first term and followed up after 3-monthes at the beginning of the second term. Questionnaires included assessment of depression, anxiety, stress, self-efficacy, and satisfaction with life. Results: Depression, anxiety, stress, and satisfaction with life were improved significantly at the beginning of the second term, whereas self-efficacy did not change significantly. The medical, female, and third-year student subgroups had the most significant changes. Depression and stress were significantly changed at the beginning of the second term in most demographic subgroups. Conclusion: Preclinical medical and dental students have different psychological health levels at different times of the same academic year. It is recommended to consider time of data collection when analyzing the results of such studies.

Outcomes in gastric and junctional cancer using neoadjuvant and adjuvant chemotherapy (epirubicin, oxaliplatin, and capecitabine) and radical surgery

Background The MAGIC/UK Medical Research Council (MRC) trial set the standard of care for treatment of resectable gastric and junctional adenocarcinoma, demonstrating that perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (ECF) confers a survival benefit over surgery alone. The randomized ECF for advanced and locally advanced esophagogastric cancer (REAL-2) trial showed that, in the metastatic setting, the EOX regimen (epirubicin, oxaliplatin and capecitabine) is as effective as ECF, with a favourable toxicity profile. Methods Consecutive patients with resectable gastric or junctional adenocarcinoma treated with perioperative EOX, between 2007 and 2012, were retrospectively analysed. Results Fifty-nine patients (12 female, 47 male), commenced EOX therapy; 47 underwent surgery. A good pathological response was seen in 34 %, (16/47). Disease recurrence occurred in 19 patients (19/47, 40 %). Median overall survival was 22 months, with 4-year survival of 47 %. Chemotoxicities were consistent with those previously reported for this regimen. Conclusion This study in a high-volume centre demonstrates that EOX in resectable gastric and junctional adenocarcinoma is associated with a reasonable safety profile, and efficacy consistent with that reported for ECF.

Microparticle-mediated gene delivery for the enhanced expression of a 19-KDa fragment of merozoite surface protein 1 of Plasmodium falciparum

The 19 kDa carboxyl-terminal fragment of merozoite surface protein 1 (MSP119) is a major component of the invasion-inhibitory response in individual immunity to malaria. A novel ultrasonic atomization approach for the formulation of biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles of malaria DNA vaccines encoding MSP119 is presented here. After condensing the plasmid DNA (pDNA) molecules with a cationic polymer polyethylenimine (PEI), a 40 kHz ultrasonic atomization frequency was used to formulate PLGA microparticles at a flow rate of 18 mL h1. High levels of gene expression and moderate cytotoxicity in COS-7 cells were achieved with the condensed pDNA at a nitrogen to phosphate (N/P) ratio of 20, thus demonstrating enhanced cellular uptake and expression of the transgene. The ability of the microparticles to convey pDNA was examined by characterizing the formulated microparticles. The microparticles displayed Z-average hydrodynamic diameters of 1.50-2.10 lm and zeta potentials of 17.8-23.2 mV. The encapsulation efficiencies were between 78 and 83%, and 76 and 85% of the embedded malaria pDNA molecules were released under physiological conditions in vitro. These results indicate that PLGA-mediated microparticles can be employed as potential gene delivery systems to antigen-presenting cells in the prevention of malaria.

The effect of transforming growth factor β1 gene polymorphisms in ankylosing spondylitis

Objectives. To determine whether genetic polymorphisms in or near the transforming growth factor β1 (TGFB1) locus were associated d with susceptibility to or severity of ankylosing spondylitis (AS). Methods. Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index). Results. A weak association was noted between the rare TGFB1 + 1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/ +915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. Conclusion. This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.

Conformational flexibility in androgenic steroids - the structure of a new form of (+)-17-beta-hydroxy-19-nor-4-androsten-3-one (19-nortestosterone), c18h26o2

The structure and conformation of a second crystalline modification of 19-nortestosterone has been determined by X-ray methods. M r = 274, monoclinic P2 l, a=9.755(2), b= 11.467(3), c= 14.196(3)/L fl=101.07(2) ° , V=1558.4 (8) A 3, Z=4, Ox= I. 168 g cm -3, Mo Ka, 2 = 0.7107 ,/k, ~ = 0.80 cm -l, F(000) = 600, T= 300 K. R = 0.060 for 2158 observed reflections. The two molecules in the asymmetric unit show significant differences in the A-ring conformation from that of the previously reported form of the title compound [Precigoux, Busetta, Courseille & Hospital (1975). Acta Cryst. B31, 1527-1532]. The l a,2fl-half-chair conformation of the A ring increases its conformational freedom compared with testosterone.