The most creative organization in the world? The BBC, 'creativity' and managerial style

The managerial styles of two BBC directors-general, John Birt and Greg Dyke, have often been contrasted but not so far analysed from the perspective of their different views of 'creative management'. This article first addresses the orthodox reading of 'Birtism'; second, it locates Dyke's 'creative' turn in the wider context of fashionable neo-management theory and UK government creative industries policy; third, it details Dyke's drive to change the BBC's culture; and finally, it concludes with some reflections on the uncertainties inherent in managing a creative organisation

Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy

INTRODUCTION: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults and is a leading cause of end-stage renal disease due to glomerulonephritis. Primary MN has a strong male predominance, accounting for approximately 65% of cases; yet, currently associated genetic loci are all located on autosomes. Previous reports of familial MN have suggested the existence of a potential X-linked susceptibility locus. Identification of such risk locus may provide clues to the etiology of MN. METHODS: We identified 3 families with 8 members affected by primary MN. Genotyping was performed using single-nucleotide polymorphism microarrays, and serum was sent for anti-phospholipase A2 receptor (PLA2R) antibody testing. All affected members were male and connected through the maternal line, consistent with X-linked inheritance. Genome-wide multipoint parametric linkage analysis using a model of X-linked recessive inheritance was conducted, and genetic risk scores (GRSs) based on known MN-associated variants were determined. RESULTS: Anti-PLA2R testing was negative in all affected family members. Linkage analysis revealed a significant logarithm of the odds score (3.260) on the short arm of the X chromosome at a locus of approximately 11 megabases (Mb). Haplotype reconstruction further uncovered a shared haplotype spanning 2 Mb present in all affected individuals from the 3 families. GRSs in familial MN were significantly lower than in anti-PLA2R–associated MN and were not different from controls. CONCLUSIONS: Our study identifies linkage of familial membranous nephropathy to chromosome Xp11.3-11.22. Family members affected with MN have a significantly lower GRS than individuals with anti-PLA2R–associated MN, suggesting that X-linked familial MN represents a separate etiologic entity

Is Cerebroplacental Ratio A Marker of Impaired Fetal Growth Velocity and Adverse Pregnancy Outcome?

BACKGROUND: The cerebroplacental ratio has been proposed as a marker of failure to reach growth potential near term. Low cerebroplacental ratio, regardless of the fetal size, is independently associated with the need for operative delivery for presumed fetal compromise and with neonatal unit admission at term. OBJECTIVE: The main aim of this study was to evaluate whether the cerebroplacental ratio at term is a marker of reduced fetal growth rate. The secondary aim was to investigate the relationship between low cerebroplacental ratio at term, reduced fetal growth velocity and adverse pregnancy outcome. DESIGN: retrospective cohort study of singleton pregnancies in a tertiary referral center. The abdominal circumference was measured at 20-24 weeks' gestation, and both abdominal circumference and fetal Dopplers recorded at or beyond 35 weeks, within two weeks of delivery. Abdominal circumference and birthweight values were converted into Z scores and centiles, respectively, and fetal Doppler parameters into multiples of median, adjusting for gestational age. Abdominal circumference growth velocity was quantified using the difference in abdominal circumference Z score, comparing the scan at or beyond 35 weeks with the scan at 20-24 weeks. Both univariable and multivariable logistic regression analyses were performed to investigate the association between low cerebroplacental ratio, low abdominal circumference growth velocity (in the lowest decile), and to identify and adjust for potential confounders. As a sensitivity analysis, we refitted the model excluding the data on pregnancies with small for gestational age neonates. RESULTS: The study included 7944 pregnancies. Low cerebroplacental ratio multiples of median was significantly associated with both low abdominal circumference growth velocity (adjusted OR 2.10; 95%CI 1.71-2.57, p<0.001) and small for gestational age (adjusted OR 3.60; 95%CI 3.04-4.25, p<0.001). After the exclusion of pregnancies resulting in small for gestational age neonates, low cerebroplacental ratio multiples of median remained significantly associated with both low abdominal circumference growth velocity (adjusted OR 1.76; 95%CI 1.34-2.30, p<0.001) and birthweight centile (adjusted OR 0.99; 95%CI 0.998-0.995, p<0.001). The need for operative delivery for fetal compromise was significantly associated with low cerebroplacental ratio (adjusted OR 1.40; 95%CI 1.10-1.78, p=0.006), even after adjusting for both the umbilical artery pulsatility index multiples of median and middle cerebral artery pulsatility index multiples of median. The results were similar even after the exclusion of pregnancies resulting in small for gestational age neonates (adjusted OR 1.39; 95%CI 1.06-1.84, p=0.018). Low cerebroplacental ratio multiples of median remained significantly associated with the risk of operative delivery for presumed fetal compromise (p<0.001), even after adjusting for the known antenatal and intrapartum risk factors. These associations persisted even after exclusion of small for gestational age births. In appropriate for gestational age sized fetuses, abdominal circumference growth velocity was significantly lower in those with low cerebroplacental ratio multiples of median than in those with normal cerebroplacental ratio multiples of median (p<0.001). CONCLUSION: Cerebroplacental ratio is a marker of impaired fetal growth velocity and adverse pregnancy outcome, even in fetuses whose size is considered appropriate using conventional biometry

Joint maintenance-inventory optimisation of parallel production systems

We model a joint inspection and spare parts inventory policy for maintaining machines in a parallel system, where simultaneous downtime seriously impacts upon production performance and has a significant financial consequence. This dependency between system components means that analysis of realistic maintenance models is intractable. Therefore we use simulation and a numerical optimisation tool to study the cost-optimality of several policies. Inspection maintenance is modelled using the delay-time concept. Critical spare parts replenishment is considered using several variants of a periodic review policy. In particular, our results indicate that the cost-optimal policy is characterised by equal frequencies of inspection and replenishment, and delivery of spare parts that coincides with maintenance intervention. In general, our model provides a framework for studying the interaction of spare parts ordering with maintenance scheduling. The sensitivity analysis that we present offers insights for the effective management of such parallel systems, not only in a paper-making plant, which motivates our modelling development, but also in other manufacturing contexts

Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants.

Context: Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation. Design: Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation. Setting: Hospital antenatal clinics. Participants: In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. Interventions: 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery. Main Outcome Measure: 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele]. Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (β = -5.2 nmol/L; 95% CI, -8.2 to -2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not. Conclusions: Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity

Targeting the X Chromosome during Spermatogenesis Induces Y Chromosome Transmission Ratio Distortion and Early Dominant Embryo Lethality in Anopheles gambiae

We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome–carrying spermatozoa. Notably, these male mosquitoes also induced complete early dominant embryo lethality in crosses with wild-type females. Morphological and molecular data indicated that all spermatozoa, irrespectively of the inheritance of the transgene, carried a substantial amount of I-PpoI protein that could attack the maternally inherited chromosome X of the embryo. Besides the obvious implications for implementing vector control measures, our data demonstrated the feasibility of generating synthetic sex distorters and revealed the intriguing possibility of manipulating maternally inherited genes using wild-type sperm cells carrying engineered endonucleases

Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial.

BACKGROUND: Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation. METHODS: The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25-100 nmol/L at 10-17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007-001716-23. FINDINGS: Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3-62·8] vs 60·5 g [59·3-61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related. INTERPRETATION: Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited. FUNDING: Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research

European Cystic Fibrosis Society standards of care: best practice guidelines

Specialised CF care has led to a dramatic improvement in survival in CF: in the last four decades, well above what was seen in the general population over the same period. With the implementation of newborn screening in many European countries, centres are increasingly caring for a cohort of patients who have minimal lung disease at diagnosis and therefore have the potential to enjoy an excellent quality of life and an even greater life expectancy than was seen previously. To allow high quality care to be delivered throughout Europe, a landmark document was published in 2005 that sets standards of care. Our current document builds on this work, setting standards for best practice in key aspects of CF care. The objective of our document is to give a broad overview of the standards expected for screening, diagnosis, pre-emptive treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support. For comprehensive details of clinical care of CF, references to the most up to date European Consensus Statements, Guidelines or Position Papers are provided in Table 1. We hope that this best practice document will be useful to clinical teams both in countries where CF care is developing and those with established CF centres

Diversity in collaborative research communities: a multicultural, multidisciplinary thesis writing group in public health

Writing groups for doctoral students are generally agreed to provide valuable learning spaces for Ph.D. candidates. Here an academic developer and the eight members of a writing group formed in a Discipline of Public Health provide an account of their experiences of collaborating in a multicultural, multidisciplinary thesis writing group. We consider the benefits of belonging to such a group for Ph.D. students who are operating in a research climate in which disciplinary boundaries are blurring and where an increasing number of doctoral projects are interdisciplinary in nature; in which both academic staff and students come from enormously diverse cultural and language backgrounds; and in which teamwork, networking and collaboration are prized but not always proactively facilitated. We argue that doctoral writing groups comprising students from diverse cultural and disciplinary backgrounds can be of significant value for postgraduates who wish to collaborate on their own academic development to improve their research writing and communication skills; at the same time, such collaborative work effectively builds an inclusive, dynamic research community.Cally Guerin, Vicki Xafis, Diana V. Doda, Marianne H. Gillam, Allison J. Larg, Helene Luckner, Nasreen Jahan, Aris Widayati and Chuangzhou X

Ultrasound Evidence of Early Fetal Growth Restriction after Maternal Malaria Infection

BACKGROUND: Intermittent preventive treatment (IPT), the main strategy to prevent malaria and reduce anaemia and low birthweight, focuses on the second half of pregnancy. However, intrauterine growth restriction may occur earlier in pregnancy. The aim of this study was to measure the effects of malaria in the first half of pregnancy by comparing the fetal biparietal diameter (BPD) of infected and uninfected women whose pregnancies had been accurately dated by crown rump length (CRL) before 14 weeks of gestation. METHODOLOGY/PRINCIPAL FINDINGS: In 3,779 women living on the Thai-Myanmar border who delivered a normal singleton live born baby between 2001-10 and who had gestational age estimated by CRL measurement <14 weeks, the observed and expected BPD z-scores (<24 weeks) in pregnancies that were (n = 336) and were not (n = 3,443) complicated by malaria between the two scans were compared. The mean (standard deviation) fetal BPD z-scores in women with Plasmodium (P) falciparum and/or P.vivax malaria infections were significantly lower than in non-infected pregnancies; -0.57 (1.13) versus -0.10 (1.17), p<0.001. Even a single or an asymptomatic malaria episode resulted in a significantly lower z-score. Fetal female sex (p<0.001) and low body mass index (p = 0.01) were also independently associated with a smaller BPD in multivariate analysis. CONCLUSIONS/SIGNIFICANCE: Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy