bluuebunny/crossref_metadata_2025 huggingface dataset:
Ex Vivo Expansion of Cord Blood Progenitors
Authors: Piacibello W. , Sanavio F. , Severino A. , Garetto L. , Danè A. , Gammaitoni L. , Aglietta M.
Published: August 2011

Human umbilical cord blood contains abundant primitive and committed hematopoietic progenitors; in addition, the general availability and the ease of procurement make cord blood a very attractive alternative source of transplantable hematopoietic tissue. However, the major limitation to a widespread use of cord blood for transplantation lays in its limited volume. For such a reason, until now, cord blood transplant has been mainly restricted to children and small size adults. Ex vivo expansion of cord blood stem cells could make the use of cord blood transplant feasible also for adult patients. Recently we developed a stroma‐free culture system in which a progressive, increasingly greater production of hemopoietic progenitors belonging to all the hematopoietic lineages was sustained for over six months. A similar sustained and prolonged expansion of the most primitive stem cells that can be detected in vitro (LTC‐IC), was also documented.

The extremely prolonged maintenance and the massive expansions suggest that extensive self‐renewal and little differentiation can be triggered in vitro by FLT3/FLK2 ligand (FL) plus c‐mpl ligand (Thrombopoietin) and this could represent a first step towards the implementation of clinical expansion‐transplantation strategies.
In Vitro And in Vivo Expansion of Stem Cell Populations
Authors: Wagemaker G.
Published: August 2011

Expansion of hemopoietic stem cells occurs in vivo following transplantation of limited numbers of bone marrow cells or of highly purified stem cells. Stem cell expansion can in principle be achieved in vitro and also be promoted in vivo by growth factor treatment, notably with thrombopoietin. Advances in identification of stromal elements, growth factors and culture conditions that stimulate immature hemopoietic stem cell proliferation may result in effective stem cell expansion protocols and contribute to efficient retrovirally mediated gene transfer. In vivo expansion of immature cells by growth factor treatment may both be a valid alternative and an adjuvant to in vitro expansion.
The CD34 Molecule and Hematopoietic Progenitor Cell Studies ‐ a Challenge in Clinical Medicine
Authors: Egeland T.
Published: August 2011

The CD34 molecule, which is expressed at various levels on virtually all human hematopoietic progenitor cells (HPC), is a heavy glycosylated molecule with many different epitopes. A large series of CD34‐specific monoclonal antibodies specific for different epitopes has been generated. Some of these antibodies do not react with particular HPC subpopulations. Thus, the antibodies used for HPC enumeration and isolation have to be carefully chosen with respect to what is aimed at.
Analysis of CD34‐Expressing Cells in Clinical Practice
Authors: Serke S. , Beyer J. , Rick O. , Schwella N. , Meyer O. , Hildebrandt M. , Huhn D.
Published: August 2011

The flow cytometric determination of haemopoietic cells defined as CD34‐ expressing cells has greatly added to the improvement of the management of harvesting circulating haemopoietic cells for subsequent autologous reinfusion in the setting of high‐dose chemo/(radio)‐therapy. Additionally, this flow cytometric determination has replaced, in some institutions, the in‐vitro culture test for CFU‐GM as the measure to estimate the haemopoietic potential of the cells to be reinfused/transplanted.
Mutated Ras Peptides as Vaccines in Immunotherapy of Cancer
Authors: Gjertsen M.K. , Gaudernack G.
Published: August 2011

Mutations in codon 12 and 13 of K‐RAS are frequently found in human cancer, including pancreatic‐ and colorectal adenocarcinomas. T cell responses specific for individual RAS mutations can be elicited in vitro by stimulation with synthetic peptides and in vivo following vaccination with antigen presenting cells pulsed ex vivo with synthetic peptides. The peptide‐responding T cells are capable of responding to intact p21 ras, and can recognise and kill tumour cell lines and isolated tumour cells harbouring the corresponding RAS mutation. The responding cells can be of both CD4+ and CD8+ phenotype, and these T cell subsets recognise nested epitopes within the vaccine peptides. Mutant ras peptides are therefore possibly an important vaccine for specific immunotherapy in patients with pancreatic and colorectal carcinomas, and are currently being tested in vivo together with GM‐CSF as an adjuvant in these cancer patients.
GMP in Blood Collection and Processing
Authors: Wagstaff W.
Published: August 2011

The principles of Good Manufacturing Practice have, in the main, been universally developed for the guidance of the pharmaceutical industry rather than for transfusion services. However, these rules and guides are increasingly being adapted for use in blood centres, in the production of labile blood components and of plasma for fractionation. The guide for pharmaceutical industries produced by the commission of the European Communities is used as a model here, the nine basic requirements being those applicable to Quality Management, personnel, premises and equipment, document, production, Quality Control, contract manufacture and analysis, complaints and product recall, and self‐ inspection. Though having more direct application to the production laboratory preparing blood components, the majority of these requirements and principles are also directly applicable to all of the activities involved in blood collection.
Effectiveness of semantic therapy for word‐finding difficulties in pupils with persistent language impairments: a randomized control trial
Authors: Ebbels Susan H. , Nicoll Hilary , Clark Becky , Eachus Beth , Gallagher Aoife L. , Horniman Karen , Jennings Mary , McEvoy Kate , Nimmo Liz , Turner Gail
Published: August 2011

Background: Word‐finding difficulties (WFDs) in children have been hypothesized to be caused at least partly by poor semantic knowledge. Therefore, improving semantic knowledge should decrease word‐finding errors. Previous studies of semantic therapy for WFDs are inconclusive.

Aims: To investigate the effectiveness of semantic therapy for secondary school‐aged pupils with WFDs using a randomized control trial with blind assessment.

Methods & Procedures: Fifteen participants with language impairments and WFDs (aged 9;11–15;11) were randomly assigned to a therapy versus waiting control group. In Phase 1 the therapy group received two 15‐min semantic therapy sessions per week for 8 weeks with their usual speech and language therapist. Therapy for each participant targeted words from one of three semantic categories (animals, food, clothes). All participants were tested pre‐ and post‐phase 1 therapy on the brief version of the Test of Adolescent Word Finding (TAWF), semantic fluency and the Test of Word Finding in Discourse (TWFD). In Phase 2 the waiting control group received the same therapy as the original therapy group, which received therapy targeted at other language areas. Testing after Phase 2 aimed to establish whether the waiting control group made similar progress to the original therapy group and whether the original therapy group maintained any gains.

Outcomes & Results: The original therapy group made significant progress in standard scores on the TAWF (d= 0.94), which was maintained 5 months later. However, they made no progress on the semantic fluency or discourse tests. Participants in the waiting control group did not make significant progress on the TAWF in Phase 1 when they received no word‐finding therapy. However, after Phase 2, when they received the therapy, they also made significant progress (d= 0.81). The combined effect of therapy over the two groups was d= 1.2. The mean standard scores on the TAWF were 67 pre‐therapy and 77 post‐therapy.

Conclusions & Implications: Four hours of semantic therapy on discrete semantic categories led to significant gains on a general standardized test of word finding, enabling the participants to begin to close the gap between their performance and that of their typically developing peers. These gains were maintained after 5 months. A small amount of therapy can lead to significant gains even with secondary aged pupils with severe language difficulties. However, further studies are needed to find ways of improving word‐finding abilities in discourse.
Utility of endtidal carbon dioxide monitoring in detection of hypoxia during sedation for brain magnetic resonance imaging in children with developmental disabilities
Authors: Kannikeswaran Nirupama , Chen Xinguang , Sethuraman Usha
Published: August 2011

Background:  We have shown previously that children with developmental disabilities have three times higher incidence of sedation‐related hypoxia when compared with normal children.

Objectives:  Our objectives were to describe the changes in endtidal carbon dioxide (ETCO2) values and the utility of ETCO2 monitoring in earlier identification of hypoxia during sedation for brain magnetic resonance imaging (MRI) in children with developmental disabilities.

Methods:  We conducted a prospective observational study of a convenience sample of 150 children with developmental disabilities aged 1–10 years who received intravenous sedation for brain MRI. Children were sedated and monitored according to the institution’s sedation protocol. We recorded ETCO2 levels, hypoxia, and adverse events during sedation. Hypoxia was defined as SpO2 < 93%. A change in ETCO2 level ≥ 10 mm Hg from presedation baseline, an intra‐sedation ≥ 50 mm Hg, and loss of capnographic waveform were considered as significant ETCO2 abnormalities.

Results:  Of the children, 80.7% (121/150) were sedated with a combination of pentobarbital and fentanyl. ETCO2 abnormalities were noted in 42.6% (64/150) of sedation encounters. Hypoxia occurred in 18% (27/150) of subjects. ETCO2 abnormalities were documented in 19(70%) patients with hypoxia before changes in pulse oximetry were noted. ETCO2 changes were noted a mean of 4.38 ± 1.89 min prior to occurrence of hypoxia.

Conclusions:  ETCO2 abnormalities and hypoxia occur commonly during sedation in children with developmental disabilities. ETCO2 monitoring is useful in early recognition of impending hypoxia during sedation in children with developmental disabilities.
Screening tools used for measuring depression among people with Type 1 and Type 2 diabetes: a systematic review
Authors: Roy T. , Lloyd C. E. , Pouwer F. , Holt R. I. G. , Sartorius N
Published: August 2011

Diabet. Med. 29, 164–175 (2012)

Background  Depression is common in patients with Type 1 or Type 2 diabetes, has a strong negative impact on the quality of life of patients and is associated with poor outcomes and higher mortality rates. Several guidelines encourage screening of patients with diabetes for depression. It is unclear which depression screening tools are currently being used in people with diabetes and which are most appropriate.

Methods  A systematic review was conducted to examine which depression screening instruments are currently being used in diabetes research, and the operating characteristics of these tools in diabetes populations. Literature searches for the period January 1970 to October 2010 were conducted using MEDLINE, PSYCH‐INFO, ASSIA, SCOPUS, ACADEMIC SEARCH COMPLETE, CINAHL and SCIENCE DIRECT.

Results  Data are presented for the 234 published studies that were examined. The Beck Depression Inventory and the Centre for Epidemiologic Studies Depression Scale were the most popular screening tools (used in 24% and 21% of studies). Information on the cultural applicability of screening tools was mostly unavailable and, where reported, included only details of the language translation process. A small number of studies reported reliability data, most of which showed moderate–good sensitivity and specificity but a high rate of false positives.

Conclusions  Although a range of depression screening tools have been used in research, there remains few data on their reliability and validity. Information on the cultural applicability of these instruments is even scantier. Further research is required in order to determine the suitability of screening tools for use in clinical practice and to address the increasing problem of co‐morbid diabetes and depression.
Effectiveness of medical nutrition treatment delivered by dietitians on glycaemic outcomes and lipid profiles of Arab, Omani patients with Type 2 diabetes
Authors: Al‐Shookri A. , Khor G. L. , Chan Y. M. , Loke S. C. , Al‐Maskari M.
Published: August 2011

Diabet. Med. 29, 236–244 (2012)

Aims  In this randomized controlled trial we evaluated the effectiveness of medical nutritional therapy on Arab patients with Type 2 diabetes in Oman delivered by a dietitian.

Methods  Patients with Type 2 diabetes (n = 170) were randomly assigned to a group receiving usual nutritional care (n = 85) or a group receiving practice guidelines nutritional care (n = 85). Anthropometric (weight, height, BMI and waist circumference) and biochemical (fasting blood glucose, HbA1c) variables were measured at baseline and after each appointment. Patients were given 1–3 appointments with a dietitian over 6 months.

Results  Those in the group receiving practice guidelines nutritional care (n = 85) had significant changes in HbA1c (−0.8%, P = 0.001), fasting plasma glucose (−1.3 mmol\l, P = 0.003) and weight (−5.1 kg, P = 0.05), whereas the patients in the usual nutritional care group (n = 85) had no significant improvements in either HbA1c (−0.4%, P = 0.248) or fasting plasma glucose (−0.2 mmol/l, P = 0.638) during the same period. We also found a significant difference between the group receiving practice guidelines nutritional care and the usual nutritional care group, respectively, in waist circumference (96.9 ± 7.9 vs. 100.0 ± 8.7 cm, P = 0.019), triglycerides levels (1.42 ± 0.58 vs. 1.98 ± 0.96 mmol\l, P = 0.001), cholesterol levels (5.1 ± 1.0 vs. 5.5 ± 0.9 mmol/l, P = 0.009) and LDL cholesterol levels (3.58 ± 0.98 vs. 3.89 ± 0.98 mmol/l, P = 0.046).

Conclusions  Medical nutrition therapy provided by dietitians to Arab patients with Type 2 diabetes in Oman resulted in significant improvements in anthropometric and biochemical outcomes in both the usual nutritional care group and the group receiving practice guidelines nutritional care. Subjects with Type 2 diabetes tended to do better with practice guidelines nutritional care than with usual nutritional care. Ongoing medical counselling in nutrition by a trained dietitian is important for better long‐term metabolic control.
Proposed new diagnostic criteria for gestational diabetes – a pause for thought?
Authors: Cundy T.
Published: August 2011

Diabet. Med. 29, 176–180 (2012)

New criteria for the diagnosis of gestational diabetes promulgated by the International Association of Diabetes and Pregnancy Study Groups (IADSPG) have been adopted by a number of groups, including the American Diabetes Association. These criteria will increase two‐ to three‐fold the number of women diagnosed with gestational diabetes and have enormous resource implications. The recommendations are derived from observations made in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, which demonstrated continuous relationships between maternal glucose tolerance and two clinically relevant outcomes of pregnancy (caesarean section rate and neonatal hypoglycaemia) and two surrogate measures (birth weight and cord C‐peptide). The recent randomized intervention studies in mild gestational diabetes indicate that the major effects of detecting and treating mild gestational diabetes are a reduction in mean birthweight of 100–140 g, and a reduction in the incidence of shoulder dystocia. However, the women included in these studies were identified using different diagnostic criteria, and it cannot be assumed that women diagnosed by the less stringent IADSPG criteria will have the same benefit. Moreover, as the majority of cases of macrosomia and shoulder dystocia occur in women with normal glucose tolerance, the real impact of diagnosing many more ‘cases’ of gestational diabetes is likely to be minimal. The concentration on mild degrees of hyperglycaemia may well be misplaced, as most of the outcomes usually attributed to gestational diabetes are more strongly associated with maternal obesity and weight gain in pregnancy. The new testing procedure (with diagnosis based on a single blood glucose measurement) will inevitably be imprecise. Given the many reservations about the new criteria an urgent but dispassionate debate is required on the risks, costs and benefits of their introduction.
IJV Partner Trustworthy Behaviour: The Role of Host Country Governance and Partner Selection Criteria
Authors: Roy Jean‐Paul
Published: August 2011

abstract

This study provides new insight into the interplay between partner‐ and institution‐level bases of trustworthy behaviour in international joint ventures (IJVs). The results of the study, based on survey and archival data collected on 144 IJVs across six Asian countries, revealed that host country governance quality directly and positively influences IJV partner trustworthy behaviour. It was also found that weak host country governance undermined the effectiveness of certain partner selection criteria in serving as a tool for establishing an IJV with a trustworthy partner. Furthermore, through distinguishing between two dimensions of trustworthiness (benevolence and competence), it was demonstrated that partner benevolence is facilitated by relationship‐oriented criteria, whereas partner competence is facilitated by task‐oriented criteria. The implications of these results for the establishment and management of IJVs are discussed.
The Theory of the Social Threshold: The Social Aspect of Accident Causation
Authors: Paterson T. T.
Published: August 2011

The majority of accidents are the result of factors which, as yet, cannot be tested for. Therefore, for large scale accident reduction we must make not only tests for accident proneness, but examine the environment where proneness which cannot be tested for can express itself. A survey of American figures demonstrates that the sustaining of many accidents in one period is not certainly prognostic of a high accident rate for the same individuals in a future period. There is regression towards the average, a spontaneous improvement (viewed statistically) over a considerable lapse of time. By further analysis it has been shown that accidents cannot be reduced beyond a certain limit by working on individuals who, over a brief period, have had a high accident rate.

The factors contributory to accident causation of all kinds are divided into three groups: intrinsic (individual), extrinsic (social), and natural, and since certain of these factors, especially social, are variable, the accident situation is dynamic not static. Accident proneness is constantly altering as the social environment changes. Following Farmer and Davis, it is concluded that social stresses give rise to emotional changes which in turn disorganise skilled activity.

This effect of social stresses can be resisted by social conditioning, but beyond a certain level or field of social conditioning, here called the social threshold, it is believed the individual becomes accident prone. It is recognised that there is a distinction between individuals who have intrinsic accident proneness detectable by battery testing, and those who are not thus detectable but, in certain environments, have a tendency to accidents. There are also those who show a history of accidents. It is proposed that these groups be called respectively accident prone, accident potential, and accident liable. The dynamic character of the accident situation explains the phenomenon of regression towards the average.
The Family Life of Old People: An Investigation in East London
Authors: Townsend Peter
Published: August 2011

‘Provision for old age has emerged as a “problem” largely because of the loosening of family ties and insistence on individual rights and privileges to the exclusion of obligations and duties which has developed so markedly in recent years. Whereas families used to accept responsibility for their old people they now expect the State to look after them … The care and attention which the family used to provide for them must be provided in some other way.’
Optimal Detection of Heterogeneous and Heteroscedastic Mixtures
Authors: Tony Cai T. , Jessie Jeng X. , Jin Jiashun
Published: August 2011

The problem of detecting heterogeneous and heteroscedastic Gaussian mixtures is considered. The focus is on how the parameters of heterogeneity, heteroscedasticity and proportion of non-null component influence the difficulty of the problem. We establish an explicit detection boundary which separates the detectable region where the likelihood ratio test is shown to detect the presence of non-null effects reliably from the undetectable region where no method can do so. In particular, the results show that the detection boundary changes dramatically when the proportion of non-null component shifts from the sparse regime to the dense regime. Furthermore, it is shown that the higher criticism test, which does not require specific information on model parameters, is optimally adaptive to the unknown degrees of heterogeneity and heteroscedasticity in both the sparse and the dense cases.
Augmented Designs to Assess Principal Strata Direct Effects
Authors: Mattei Alessandra , Mealli Fabrizia
Published: August 2011

Many studies involving causal questions are often concerned with understanding the causal pathways by which a treatment affects an outcome. Thus, the concept of ‘direct’versus‘indirect’ effects comes into play. We tackle the problem of disentangling direct and indirect effects by investigating new augmented experimental designs, where the treatment is randomized, and the mediating variable is not forced, but only randomly encouraged. There are two key features of our framework: we adopt a principal stratification approach, and we mainly focus on principal strata effects, avoiding involving a priori counterfactual outcomes. Using non-parametric identification strategies, we provide a set of assumptions, which allow us to identify partially the causal estimands of interest: the principal strata direct effects. Some examples are shown to illustrate our design and causal estimands of interest. Large sample bounds for the principal strata average direct effects are provided, and a simple hypothetical example is used to show how our augmented design can be implemented and how the bounds can be calculated. Finally our augmented design is compared and contrasted with a standard randomized design.
Will improving wastewater treatment impact shorebirds? Effects of sewage discharges on estuarine invertebrates and birds
Authors: Alves J. A. , Sutherland W. J. , Gill J. A.
Published: August 2011

Human communities often discharge wastewaters into estuaries, influencing their organic and pollutant loading, benthic community and trophic structure. The implementation of the Water Framework Directive has encouraged the treatment of wastewater discharges across European estuaries, but the implications for invertebrate and waterbird communities are poorly understood. We explore the effects of untreated sewage discharges on the distribution and abundance of foraging black‐tailed godwits Limosa limosa and their main benthic prey (bivalves and polychaetes) on the Tejo estuary in Portugal, a major European Special Protection Area with ongoing wastewater improvements. Patches of mudflat in close proximity to sewage streams (<30 m) can support polychaete densities and biomass that are an order of magnitude higher than more distant sites (>70 m), and godwits foraging in these areas can attain the highest intake rates recorded for the estuary. However, high intake rates can also be attained on bivalve prey, and bivalve biomass and density increase slightly with distance from sewage streams. As the organic input from sewage outfalls influences invertebrate abundance and godwit foraging rates over relatively small areas, the ongoing implementation of a sewage treatment network on the Tejo estuary seems likely to have only a limited impact on the wintering godwit population. The localized effect of untreated sewage discharges on benthic communities suggests that the implications for predatory birds are relatively minor where alternative prey are available, but may be more severe in locations with more depauperate, polychaete‐dominated invertebrate communities.
FE65 proteins regulate NMDA receptor activation‐induced amyloid precursor protein processing
Authors: Suh Jaehong , Lyckman Alvin , Wang Lirong , Eckman Elizabeth A. , Guénette Suzanne Y.
Published: August 2011

J. Neurochem. (2011) 119, 377–388.

Amyloid precursor protein (APP) family members and their proteolytic products are implicated in normal nervous system function and Alzheimer’s disease pathogenesis. APP processing and Aβ secretion are regulated by neuronal activity. Various data suggest that NMDA receptor (NMDAR) activity plays a role in both non‐amyloidogenic and amyloidogenic APP processing depending on whether synaptic or extrasynaptic NMDARs are activated, respectively. The APP‐interacting FE65 proteins modulate APP trafficking and processing in cell lines, but little is known about their contribution to APP trafficking and processing in neurons, either in vivo or in vitro. In this study, we examined the contribution of the FE65 protein family to APP trafficking and processing in WT and FE65/FE65L1 double knockout neurons under basal conditions and following NMDAR activation. We report that FE65 proteins facilitate neuronal Aβ secretion without affecting APP fast axonal transport to pre‐synaptic terminals. In addition, FE65 proteins facilitate an NMDAR‐dependent non‐amyloidogenic APP processing pathway. Generation of high‐molecular weight (HMW) species bearing an APP C‐terminal epitope was also observed following NMDAR activation. These HMW species require proteasomal and calpain activities for their accumulation. Recovery of APP polypeptide fragments from electroeluted HMW species having molecular weights consistent with calpain I cleavage of APP suggests that HMW species are complexes formed from APP metabolic products. Our results indicate that the FE65 proteins contribute to physiological APP processing and accumulation of APP metabolic products resulting from NMDAR activation.
Age‐related decline in osteoblastogenesis and 1α‐hydroxylase/CYP27B1 in human mesenchymal stem cells: stimulation by parathyroid hormone
Authors: Geng Shuo , Zhou Shuanhu , Glowacki Julie
Published: August 2011

With aging, there is a decline in bone mass and in osteoblast differentiation of human mesenchymal stem cells (hMSCs) in vitro. Osteoblastogenesis can be stimulated with 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] and, in some hMSCs, by the precursor 25‐hydroxyvitamin D3 (25OHD3). CYP27B1/1α‐hydroxylase activates 25OHD3 and, to a variable degree, hMSCs express CYP27B1. In this study, we tested the hypotheses (i) that age affects responsiveness to 25OHD3 and expression/activity of CYP27B1 in hMSCs and (ii) that parathyroid hormone (PTH) upregulates CYP27B1 in hMSCs, as it does in renal cells. There were age‐related declines in osteoblastogenesis (n = 8, P = 0.0286) and in CYP27B1 gene expression (n = 27, r = −0.498; P = 0.008) in hMSCs. Unlike hMSCs from young subjects (≤50 years), hMSCs from older subjects (≥55 years) were resistant to 25OHD3 stimulation of osteoblastogenesis. PTH1‐34 (100 nm) provided hMSCs with responsiveness to 25OHD3 (P = 0.0313, Wilcoxon matched pairs test) and with two episodes of increased 1,25(OH)2D3 synthesis, of cAMP response element binding protein (CREB) activation, and of CYP27B1 upregulation. Both increases in CYP27B1 expression by PTH were obliterated by CREB‐siRNA or KG‐501 (which specifically inhibits the downstream binding of activated CREB). Only the second period of CREB signaling was diminished by AG1024, an inhibitor of insulin‐like growth factor‐I receptor kinase. Thus, PTH stimulated hMSCs from elders with responsiveness to 25OHD3 by upregulating expression/activity of CYP27B1 and did so through CREB and IGF‐I pathways.
Oncogenes induce senescence with incomplete growth arrest and suppress the DNA damage response in immortalized cells
Authors: Sherman Michael Y. , Meng Le , Stampfer Martha , Gabai Vladimir L. , Yaglom Julia A.
Published: August 2011

Activation of the Her2 (ErbB2) oncogene is implicated in the development of breast, ovary and other cancers. Here, we show that expression of NeuT, a mutant‐activated rodent isoform of Her2, in immortalized breast epithelial cells, while promoting senescence‐associated morphological changes, up‐regulation of senescence‐associated β‐galactosidase activity, and accumulation of the cyclin‐dependent kinase inhibitor p21, failed to trigger the major senescence end‐point, i.e. permanent growth arrest. Similar senescence‐associated phenotype with incomplete growth arrest, which we dubbed senescence with incomplete growth arrest (SWING), could also be triggered by the expression of the Ras oncogene. SWING phenotype was stable, and persisted in tumor xenografts established from NeuT‐transduced cells. Furthermore, a significant population of cells in SWING state was found in tumors in the MMTV/NeuT transgenic mouse model. SWING cells showed downregulation of histone H2AX, critical for repair of double‐stranded DNA breaks, and impaired activation of Chk1 kinase. Overall, SWING cells were characterized by increased DNA instability and hypersensitivity to genotoxic stresses. We propose that the SWING state could be a stage in the process of cancer development.
Genistein aglycone, a soy‐derived isoflavone, improves skin changes induced by ovariectomy in rats
Authors: Polito Francesca , Marini Herbert , Bitto Alessandra , Irrera Natasha , Vaccaro Mario , Adamo Elena Bianca , Micali Antonio , Squadrito Francesco , Minutoli Letteria , Altavilla Domenica
Published: August 2011

BACKGROUND AND PURPOSE Ovariectomy accelerates age‐related skin changes as adequate oestrogen levels are required to control structural integrity and functional capacity of skin. Genistein, a soy‐derived isoflavone, has been tested in anti‐ageing cosmetic preparations with interesting results on skin elasticity, photoaging and skin cancer prevention. We investigated the effects of genistein aglycone and compared them with systemic raloxifene hydrochloride and 17‐α‐ethinyloestradiol on skin changes in aged, ovariectomized (OVX) rats.

EXPERIMENTAL APPROACH Six months after ovariectomy, rats were randomly allocated to different groups and treated, daily, with genistein aglycone (1 and 10 mg·kg−1 s.c.), raloxifene hydrochloride (0.05 and 0.5 mg·kg−1 s.c.) or 17‐α‐ethinyloestradiol (0.003 and 0.03 mg·kg−1 s.c.) for 12 weeks. Controls were untreated OVX and sham OVX rats. At the end of the treatment period, a skin biopsy was carried out and skin samples were assessed for molecular, histological and functional changes.

KEY RESULTS Skin samples of untreated OVX rats showed a decrease in TGF‐β1, VEGF, MMP‐2, MMP‐9, tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2 compared with sham OVX rats. All the treatments significantly restored this depressed molecular profile revealed in OVX rats. Genistein aglycone, 1 mg·kg−1, also significantly increased the thickness of collagen and breaking strength of skin in the OVX rats.

CONCLUSIONS AND IMPLICATIONS Relatively long‐term, systemic treatment with genistein aglycone shows comparable efficacy to oestrogen in reversing some molecular, histological and functional changes of the skin associated with ovariectomy in aged rats. This suggests that genistein aglycone might be an effective alternative therapy for the management of age‐related skin changes in postmenopausal women.
PHASED OSCILLATIONS IN CELL NUMBERS AND NITRATE IN BATCH CULTURES OF ALEXANDRIUM TAMARENSE (DINOPHYCEAE)1
Authors: Collos Yves , Hadjadji Imene , Plisson Benoit , Cecchi Philippe , Laabir Mohamed , Bechemin Christian , Masseret Estelle
Published: August 2011

Alexandrium tamarense (M. Lebour) Balech strains isolated in spring 2007 from a single bloom in Thau lagoon have been grown in nonaxenic artificial media. For three strains showing large oscillations in biomass (crashes followed by recoveries) on a scale of several days, a significant relationship was observed between changes in cell densities (as in vivo fluorescence) and changes in nitrate concentrations. Increases in cell densities were accompanied by decreases in nitrate, while decreases in cell densities corresponded to increases in nitrate, presumably due to nitrification. Net increases in nitrate could reach up to 15 μmol N · L−1 · d−1 indicating a very active nitrifying archaeal/bacterial population. However, following population crashes, algal cells can recover and attain biomass levels similar to those reached during the first growth phase. This finding indicates that those archaea/bacteria do not compete for nutrients or do not hamper algal growth under those conditions. In contrast to diatoms, dinoflagellates such as A. tamarense do not excrete/exude dissolved organic matter, thus preventing excessive bacterial growth. This mechanism could help explain the recovery of this species in the presence of bacteria.
Application of implicit attitude measures to the blood donation context
Authors: Warfel Regina M. , France Christopher R. , France Janis L.
Published: August 2011

BACKGROUND: Past blood donation research has relied on explicit (self‐report) measures to understand blood donation motivations, but has not yet considered the inherent implicit or automatic processing involved in decision‐making. This study addresses this limitation by introducing and validating two novel implicit measures of blood donation attitudes.

STUDY DESIGN AND METHODS: Healthy young adults (n = 253) performed both image and word versions of a Single Target Implicit Association Test (ST‐IAT) and then completed self‐report measures of blood donation attitudes, blood and needle fears, social desirability, and donation intention.

RESULTS: These results affirmed the validity of the blood donation ST‐IATs in at least three ways. First, as expected, nondonors demonstrated more negative implicit donation attitudes than donors. Second, the implicit measures were significantly related in expected directions with explicit measures of donation attitudes as well as blood and needle fears. Finally, implicit donation attitudes were significantly related to donation intention, and the Image ST‐IAT (but not the Word ST‐IAT) significantly enhanced prediction of donation intention over and above needle fears and marginally enhanced prediction over and above blood fears.

CONCLUSION: Image and word versions of the blood donation ST‐IAT offer a valid method of assessing underlying automatic attitudes toward blood donation.
Riboflavin and ultraviolet light treatment potentiates vasodilator‐stimulated phosphoprotein Ser‐239 phosphorylation in platelet concentrates during storage
Authors: Schubert Peter , Culibrk Brankica , Coupland Danielle , Scammell Ken , Gyongyossy‐Issa Maria , Devine Dana V.
Published: August 2011

BACKGROUND: Pathogen reduction technologies (PRTs) were developed to improve the safety of platelet concentrates (PCs) for transfusion purposes; however, several studies report a negative impact on the in vitro and in vivo platelet (PLT) quality. Therefore, analyses of the underlying molecular processes triggered by PRT treatments are necessary to understand their effects on PLT function.

STUDY DESIGN AND METHODS: In two separate two‐arm studies PCs prepared in plasma for storage either by the leukoreduced buffy coat (BC‐PCs) or by the leukoreduced apheresis (AP‐PCs) method were treated with or without riboflavin and ultraviolet (UV) light (Mirasol; 6.24 J/mL; 265‐375 nm). Samples were drawn after treatment and after 1, 4, and 6 days of storage with subsequent analyses performed using in vitro measurements for PLT quality monitoring. Semiquantitative proteomic studies identified proteins that changed in band intensities in response to treatment or storage. Protein validation and subsequent biochemical studies were carried out by immunoblot analyses.

RESULTS: The proteomic results identified changes mainly of proteins associated with the structure and regulation of the cytoskeleton. Focusing on the vasodilator‐stimulated phosphoprotein (VASP) in AP‐PCs revealed a storage‐dependent, but treatment‐independent, delocalization and a strong treatment‐dependent phosphorylation at Ser‐239 that was also present, but to a much lesser degree in BC‐PCs. This modification correlated exponentially with PLT activation as determined by P‐selectin expression.

CONCLUSION: Treatment of PCs with Mirasol leads to the amplification of VASP Ser‐239 phosphorylation, which is linked to actin dynamics and regulation of integrin αIIbβ3 activation. This change offers one explanation for Mirasol's impact on PLT in vitro quality measures. The Ser‐239 phosphorylation level of VASP might be a useful protein marker for riboflavin and UV light–mediated PLT compromise.
Learning Foreign Sounds in an Alien World: Videogame Training Improves Non‐Native Speech Categorization
Authors: Lim Sung‐joo , Holt Lori L.
Published: August 2011

Although speech categories are defined by multiple acoustic dimensions, some are perceptually weighted more than others and there are residual effects of native‐language weightings in non‐native speech perception. Recent research on nonlinguistic sound category learning suggests that the distribution characteristics of experienced sounds influence perceptual cue weights: Increasing variability across a dimension leads listeners to rely upon it less in subsequent category learning (Holt & Lotto, 2006). The present experiment investigated the implications of this among native Japanese learning English /r/‐/l/ categories. Training was accomplished using a videogame paradigm that emphasizes associations among sound categories, visual information, and players’ responses to videogame characters rather than overt categorization or explicit feedback. Subjects who played the game for 2.5 h across 5 days exhibited improvements in /r/‐/l/ perception on par with 2–4 weeks of explicit categorization training in previous research and exhibited a shift toward more native‐like perceptual cue weights.
Theory and the Scientific Basis for Forensic Anthropology*
Authors: Boyd Clifford , Boyd Donna C.
Published: August 2011

Abstract:  Forensic anthropology has long been criticized for its lack of a strong theoretical and scientific foundation. This paper addresses this problem by examining the role of theory in forensic anthropology at different hierarchical levels (high‐level, middle‐range, and low‐level) and the relevance of various theoretical concepts (taphonomic, agency, behavioral archaeology, nonlinear systems, and methodological theories) to the interpretation of forensic contexts. Application of these theories to a case study involving the search for the WWII Goettge Patrol illustrates the explanatory power these theories offer to the interpretation of forensic events as the end product of an often complex set of environmental constraints and behavioral interactions and choices. It also emphasizes the importance of case studies in theory building and hypothesis testing. A theoretical foundation does indeed currently exist in forensic anthropology; however, a recognition and broader implementation of anthropological (archaeological) theory is warranted and will further define forensic anthropology as a scientific endeavor.
Age Estimation by Measurements of Developing Teeth: Accuracy of Cameriere’s Method on a Brazilian Sample
Authors: Fernandes Mário Marques , Tinoco Rachel Lima Ribeiro , de Braganca Daniel Pereira Parreiras , de Lima Silas Henrique Rabelo , Junior Luiz Francesquini , Junior Eduardo Daruge
Published: August 2011

Abstract:  Developing teeth are commonly the criteria used for age estimation in children and young adults. The method developed by Cameriere et al. (Int J Legal Med 2006;120:49‐52) is based on measures of teeth with open apex, and application of a formula, to estimate chronological age of children. The present study evaluated a sample of panoramic radiographs from Brazilian children from 5 to 15 years of age, to evaluate the accuracy of the method proposed by Cameriere et al. The results has proven the system reliable for age estimation, with a median residual error of −0.014 years between chronological and estimated ages (p = 0.603). There was a slight tendency to overestimate the ages of 5–10 years and underestimate the ages of 11–15 years.
In the Eye of the Beholder: Sex and Race Estimation using the Human Orbital Aperture*
Authors: Husmann Polly R. , Samson David R.
Published: August 2011

Abstract:  From the works of Broca and Krogman to modern‐day Jantz and Buikstra, the orbit has been used for both quantitative and qualitative sex and race estimation. This study evaluates the practical value of these estimations. Orbital height and breadth were measured to determine the orbital index and assess differences between men and women or black people and white people in the Hamann–Todd Collection. Replicability of these measures was also examined. Finally, a geometric morphometric study was performed to assess shape differences using the entire margin. Significant differences were found in both the index and the geomorphometric study; however, further investigation revealed that the differences were of little practical use. The measurement differences were found to be smaller than intra‐observer error, while the geometric morphometric analysis demonstrated that minimal percentage of variation in shape was attributable to group differences. Thus, these techniques should not be used to estimate sex or race.
Comparisons of Familial DNA Database Searching Strategies
Authors: Ge Jianye , Chakraborty Ranajit , Eisenberg Arthur , Budowle Bruce
Published: August 2011

Abstract:  The current familial searching strategies are generally based on either Identity‐By‐State (IBS) (i.e., number of shared alleles) or likelihood ratio (i.e., kinship index [KI]) assessments. In this study, the expected IBS match probabilities given relationships and the logic of the likelihood ratio method were addressed. Further, the false‐positive and false‐negative rates of the strategies were compared analytically or by simulations using Caucasian population data of the 13 CODIS Short Tandem Repeat (STR). IBS ≥ 15, IBS ≥ 16, KI ≥ 1000, or KI ≥ 10,000 were found to be good thresholds for balancing false‐positive and false‐negative rates. IBS ≥ 17 and/or KI ≥ 1,000,000 can exclude the majority of candidate profiles in the database, either related or not, and may be an initial screening option if a small candidate list is desired. Polices combining both IBS and KI can provide higher accuracy. Typing additional STRs can provide better searching performance, and lineage markers can be extremely useful for reducing false rates.
Comparison of the Analytical Capabilities of the BAC Datamaster and Datamaster DMT Forensic Breath Testing Devices
Authors: Glinn Michele , Adatsi Felix , Curtis Perry
Published: August 2011

Abstract:  The State of Michigan uses the Datamaster as an evidential breath testing device. The newest version, the DMT, will replace current instruments in the field as they are retired from service. The Michigan State Police conducted comparison studies to test the analytical properties of the new instrument and to evaluate its response to conditions commonly cited in court defenses. The effects of mouth alcohol, objects in the mouth, and radiofrequency interference on paired samples from drinking subjects were assessed on the DMT. The effects of sample duration and chemical interferents were assessed on both instruments, using drinking subjects and wet‐bath simulators, respectively. Our testing shows that Datamaster and DMT results are essentially identical; the DMT gave accurate readings as compared with measurements made using simulators containing standard ethanol solutions and that the DMT did not give falsely elevated breath alcohol results from any of the influences tested.
Prevalence and Effects of Violence Against Women in a Rural Community in Minia Governorate, Egypt*
Authors: Habib Sahar R. , Abdel Azim Enas K. , Fawzy Irene A. , Kamal Nashwa N. , El Sherbini Amr M.
Published: August 2011

Abstract:  This study was carried out to investigate prevalence and the characteristics of domestic violence (DV) against women in a rural area in Minia governorate, Egypt, as well as its physical and psychological consequences. Seven hundred and seventy‐two women were interviewed. Sociodemographic data were collected; the WHO questionnaire was used to identify the abuse; the Structured Clinical Interview for DSM IIIR (SCID) to detect psychiatric disorders. Abused females constituted 57.4% of the total sample. There were significant relationships between DV and low education, low income, higher number of children, and husband’s education. Psychiatric disorders occurred in 18% of the sample. There were statistically significant relationships between psychological and physical abuse of women and the occurrence of psychiatric disorders. In conclusion, DV against women was related to various negative health outcomes, and it is recommended to be given its real importance in both Forensic Medicine Council and in psychiatric assessment.
Toxicological Findings in Cases of Sexual Assault in the Netherlands*
Authors: Bosman Ingrid J. , Verschraagen Miranda , Lusthof Klaas J.
Published: August 2011

Abstract:  Reports on cases of alleged drug‐facilitated sexual assault (DFSA) have increased since the mid‐1990s. The aim of this study was to identify the extent and types of drugs found in cases of alleged sexual assault (DFSA) in the Netherlands. In total, 135 cases of alleged DFSA were identified. Most of the victims were women (94%), and the mean age of the victims was 25 years. Blood and urine samples were tested for the presence of alcohol, drugs (drugs of abuse and prescription drugs), or both. In 27% of the cases, no alcohol and/or drugs were found. With increasing time delay, more cases were found to be negative. Alcohol is the most commonly found drug followed by nonopiate analgesics, illicit drugs, and benzodiazepines. In some cases, the absence of alcohol and drugs may represent false‐negative results owing to the time delay between alleged sexual assault and sampling.
Specific Micro‐RNA Signatures for the Detection of Saliva and Blood in Forensic Body‐fluid Identification
Authors: Courts Cornelius , Madea Burkhard
Published: August 2011

Abstract:  Micro‐RNAs (miRNAs) are a class of small noncoding RNA (ncRNA) molecules with a length of 18–24 nucleotides which play an essential regulative role for many cellular processes. Evidence suggests that the miRNome is a more precise and meaningful representation of a cell type and condition than the mRNA transcriptome. To identify miRNAs that are suitable for forensic body‐fluid identification, a global screening by microarray analysis of c. 800 miRNAs of forensic blood and saliva samples was performed, and by bioinformatic processing, three differentially expressed candidate miRNAs for saliva and blood each were selected. The six candidates were then validated and confirmed via quantitative PCR. Herein, we present miRNA assays consisting of three differentially expressed miRNAs for the identification of blood (miR‐126, miR‐150, miR‐451) and saliva (miR‐200c, miR‐203, miR‐205), respectively. We conclude that miRNA extraction from forensic samples is possible and support a “proof of concept” that body‐fluid identification by miRNA analysis may become a potent forensic technique.