Monitoring and evaluation of family interventions: information on families supported to March 2010 (Research report DFE-RR044)

"This report updates and builds on the previous research by presenting and analysing FIIS [Family intervention Information system] data provided by family intervention staff up to and including 31 March 2010. The report is primarily based on simple descriptive statistics which provide a summary of the quantitative evidence. In addition statistical modelling (logistic regression) was used to look at the factors associated with successful and unsuccessful outcomes." - Page 14

Monitoring and evaluation of family interventions (Information on families supported to March 2010) RR044

Josie Dixon, Vera Schneider, Cheryl Lloyd, Alice Reeves, Clarissa White, Wojtek Tomaszewski, Rosie Green and Eleanor Irelan

Fast evaluation of appointment schedules for outpatients in health care

We consider the problem of evaluating an appointment schedule for outpatients in a hospital. Given a fixed-length session during which a physician sees K patients, each patient has to be given an appointment time during this session in advance. When a patient arrives on its appointment, the consultations of the previous patients are either already finished or are still going on, which respectively means that the physician has been standing idle or that the patient has to wait, both of which are undesirable. Optimising a schedule according to performance criteria such as patient waiting times, physician idle times, session overtime, etc. usually requires a heuristic search method involving a huge number of repeated schedule evaluations. Hence, the aim of our evaluation approach is to obtain accurate predictions as fast as possible, i.e. at a very low computational cost. This is achieved by (1) using Lindley's recursion to allow for explicit expressions and (2) choosing a discrete-time (slotted) setting to make those expression easy to compute. We assume general, possibly distinct, distributions for the patient's consultation times, which allows us to account for multiple treatment types, as well as patient no-shows. The moments of waiting and idle times are obtained. For each slot, we also calculate the moments of waiting and idle time of an additional patient, should it be appointed to that slot. As we demonstrate, a graphical representation of these quantities can be used to assist a sequential scheduling strategy, as often used in practice

Collateral-resistance to estrogen and HER-activated growth is associated with modified AKT, ERα and cell-cycle signaling in a breast cancer model

These studies were supported by grants from Cancer Research UK (C503/A5010 and C1938/A6769).Aim : A model of progressively endocrine-resistant breast cancer was investigated to identify changes that can occur in signaling pathways after endocrine manipulation. Methods : The MCF7 breast cancer model is sensitive to estrogens and anti-estrogens while variant lines previously derived from wild-type MCF7 are either relatively 17β-estradiol (E2)-insensitive (LCC1) or fully resistant to estrogen and anti-estrogens (LCC9). Results : In LCC1 and LCC9 cell lines, loss of estrogen sensitivity was accompanied by loss of growth response to transforming growth factor alpha (TGFα), heregulin-beta and pertuzumab. LCC1 and LCC9 cells had enhanced AKT phosphorylation relative to MCF7 which was reflected in downstream activation of phospho-mechanistic target of rapamycin (mTOR), phospho-S6, and phospho-estrogen receptor alpha Ser167 [ERα(Ser167)]. Both AKT2 and AKT3 were phosphorylated in the resistant cell lines, but siRNA knockdown suggested that all three AKT isoforms contributed to growth response. ERα(Ser118) phosphorylation was increased by E2 and TGFα in MCF7, by E2 only in LCC1, but by neither in LCC9 cells. Multiple alterations in E2-mediated cell cycle control were identified in the endocrine-resistant cell lines including increased expression of MYC, cyclin A1, cyclin D1, cyclin-dependent kinase 1 (CDK1), CDK2, and hyperphosphorylated retinoblastoma protein (ppRb), whereas p21 and p27 were reduced. Estrogen modulated expression of these regulators in MCF7 and LCC1 cells but not in LCC9 cells. Seliciclib inhibited CDK2 activation in MCF7 cells but not in resistant variants; in all lines, it reduced ppRb, increased p53 associated responses including p21, p53 up-regulated modulator of apoptosis (PUMA), and p53 apoptosis-inducing protein 1 (p53AIP1), inhibited growth, and produced G2/M block and apoptosis. Conclusions : Multiple changes occur with progression of endocrine resistance in this model with AKT activation contributing to E2 insensitivity and loss of ERα(Ser118) phosphorylation being associated with full resistance. Cell cycle regulation is modified in endocrine-resistant breast cancer cells, and seliciclib is effective in both endocrine-sensitive and resistant diseases.Publisher PDFPeer reviewe

Short-term memory for pictures seen once or twice

The present study is concerned with the effects of exposure time, repetition, spacing and lag on old/new recognition memory for generic visual scenes presented in a RSVP paradigm. Early memory studies with verbal material found that knowledge of total exposure time at study is sufficient to accurately predict memory performance at test (the Total Time Hypothesis), irrespective of number of repetitions, spacing or lag. However, other studies have disputed such simple dependence of memory strength on total study time, demonstrating super-additive facilitatory effects of spacing and lag, as well as inhibitory effects, such as the Ranschburg effect, Repetition Blindness and the Attentional Blink. In the experimental conditions of the present study we find no evidence of either facilitatory or inhibitory effects: recognition memory for pictures in RSVP supports the Total Time Hypothesis. The data are consistent with an Unequal-Variance Signal Detection Theory model of memory that assumes the average strength and the variance of the familiarity of pictures both increase with total study time. The main conclusion is that the growth of visual scene familiarity with temporal exposure and repetition is a stochastically independent process

Simian virus 40 vectors for pulmonary gene therapy

<p>Abstract</p> <p>Background</p> <p>Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS). Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy.</p> <p>Methods</p> <p>Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP). SV40 vectors carrying the luciferase reporter gene (SV/<it>luc) </it>were administered intratracheally immediately after sepsis induction. Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by <it>in vivo </it>light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C). Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector.</p> <p>Results</p> <p>Luc expression measured by <it>in vivo </it>light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response.</p> <p>Conclusion</p> <p>In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of <it>in vivo </it>transduction of alveolar type II cells and may thus become a future therapeutic tool.</p

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm&lt; 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

CMB-S4 Science Book, First Edition

This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales

Inflation and Dark Energy from spectroscopy at z > 2

The expansion of the Universe is understood to have accelerated during two epochs: in its very first moments during a period of Inflation and much more recently, at z < 1, when Dark Energy is hypothesized to drive cosmic acceleration. The undiscovered mechanisms behind these two epochs represent some of the most important open problems in fundamental physics. The large cosmological volume at 2 < z < 5, together with the ability to efficiently target high-$z$ galaxies with known techniques, enables large gains in the study of Inflation and Dark Energy. A future spectroscopic survey can test the Gaussianity of the initial conditions up to a factor of ~50 better than our current bounds, crossing the crucial theoretical threshold of $\sigma(f_{NL}^{\rm local})$ of order unity that separates single field and multi-field models. Simultaneously, it can measure the fraction of Dark Energy at the percent level up to $z = 5$, thus serving as an unprecedented test of the standard model and opening up a tremendous discovery space