Linear local models for monocular reconstruction of deformable surfaces.
Recovering the 3D shape of a nonrigid surface from a single viewpoint is known to be both ambiguous and challenging. Resolving the ambiguities typically requires prior knowledge about the most likely deformations that the surface may undergo. It often takes the form of a global deformation model that can be learned from training data. While effective, this approach suffers from the fact that a new model must be learned for each new surface, which means acquiring new training data, and may be impractical. In this paper, we replace the global models by linear local models for surface patches, which can be assembled to represent arbitrary surface shapes as long as they are made of the same material. Not only do they eliminate the need to retrain the model for different surface shapes, they also let us formulate 3D shape reconstruction from correspondences as either an algebraic problem that can be solved in closed form or a convex optimization problem whose solution can be found using standard numerical packages. We present quantitative results on synthetic data, as well as qualitative results on real images.


Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors.
Mutations in the MEN1 gene are associated with the multiple endocrine neoplasia syndrome type 1 (MEN1), which is characterized by parathyroid hyperplasia and tumors of the pituitary and pancreatic islets. The mechanism by which MEN1 acts as a tumor suppressor is unclear. We have recently shown that menin, the MEN1 protein product, interacts with mixed lineage leukemia (MLL) family proteins in a histone methyltransferase complex including Ash2, Rbbp5, and WDR5. Here, we show that menin directly regulates expression of the cyclin-dependent kinase inhibitors p27Kip1 and p18Ink4c. Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. Loss of function of either MLL or menin results in down-regulation of p27Kip1 and p18Ink4c expression and deregulated cell growth. These findings suggest that regulation of cyclin-dependent kinase inhibitor transcription by cooperative interaction between menin and MLL plays a central role in menin's activity as a tumor suppressor.


Use of vitamin D in chronic kidney disease patients.
Chronic kidney disease (CKD) has been recognized as a significant public health problem, with 20 million Americans, or 11% of the adult population, currently living with CKD. Life expectancy in patients with CKD is limited by the development of disturbances of mineral metabolism, which occurs in virtually all patients during the progression of their disease, and is associated with bone loss and fractures, cardiovascular disease, immune suppression, and increased mortality. As kidney disease develops, there is decreased functional renal mass and a reduction in renal 1alpha-hydroxylase activity and thus in renal production of calcitriol at very early CKD stages. Recently, a potentially important role of vitamin D receptor activation (VDRa) in the survival of patients undergoing dialysis has been suggested. Beyond the effect on parathyroid hormone suppression, the pleiotropic effect of vitamin D has been associated with improvement of cardiovascular risk factors, including increased renin activity, hypertension, inflammation, insulin resistance, diabetes, and albuminuria. However, the current K/DOQI and KDIGO recommendations limit the administration of VDRa agents for treatment of hyperparathyroidism only. The role of vitamin D administration in the different CKD stages will be discussed in this review.


Evidence that caterpillar labial saliva suppresses infectivity of potential bacterial pathogens.
Salivary enzyme, glucose oxidase (GOX) from the caterpillar Helicoverpa zea, catalyzes the conversion of glucose to gluconic acid and hydrogen peroxide. Because hydrogen peroxide has well-known antimicrobial properties, we examined whether caterpillar labial saliva could reduce the infectivity of bacterial pathogens. We examined the effects of caterpillar saliva on the growth of two bacteria species Serratia marcescens and Pseudomonas aeruginosa. Wells formed in LB agar contained a solution of salivary gland extract (Sx) and glucose, GOX and glucose, Sx only, GOX only, or glucose only. After 18 h of incubation, the diameter of cleared bacteria was measured. Wells treated with only GOX, Sx, or glucose showed no measurable area of clearing, while wells treated with GOX with glucose or Sx with glucose had considerable clearing. To determine if saliva could provide protection to caterpillars in vivo, a surgery was performed on caterpillars that prevented the secretion of labial saliva. Caterpillars were fed a diet containing either no added bacteria or treated with high levels of S. marcescens or P. aeruginosa. Caterpillars that could not secrete saliva had significantly higher levels of mortality when feeding on diet treated with either bacterium than caterpillars that could secrete saliva when feeding on equal levels of bacteria-treated diet. Our evidence demonstrates for the first time that insect saliva in situ can provide protection against bacterial pathogens and that the salivary enzyme GOX appears to provide the antimicrobial properties.


Loss of the six3/6 controlling pathways might have resulted in pinhole-eye evolution in Nautilus.
Coleoid cephalopods have an elaborate camera eye whereas nautiloids have primitive pinhole eye without lens and cornea. The Nautilus pinhole eye provides a unique example to explore the module of lens formation and its evolutionary mechanism. Here, we conducted an RNA-seq study of developing eyes of Nautilus and pygmy squid. First, we found that evolutionary distances from the common ancestor to Nautilus or squid are almost the same. Although most upstream eye development controlling genes were expressed in both species, six3/6 that are required for lens formation in vertebrates was not expressed in Nautilus. Furthermore, many downstream target genes of six3/6 including crystallin genes and other lens protein related genes were not expressed in Nautilus. As six3/6 and its controlling pathways are widely conserved among molluscs other than Nautilus, the present data suggest that deregulation of the six3/6 pathway led to the pinhole eye evolution in Nautilus.


Metabolic syndrome and the risk of ischemic heart disease and stroke among Japanese men and women.
Limited evidence was available on the metabolic syndrome and risk of cardiovascular disease in Asia. The purpose of this study is to examine the association of the metabolic syndrome and risk of ischemic cardiovascular disease in Japanese men and women. We conducted an 18-year prospective study of 9087 Japanese people aged 40 to 69 years (3595 men and 5492 women), initially free of ischemic heart disease or stroke. During follow-up, there were 116 (74 men and 42 women) cases of ischemic heart disease and 256 (144 men and 112 women) ischemic strokes. Metabolic syndrome was defined by the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII), with the presence of >/=3 of the following factors: (1) serum triglycerides >/=1.69 mmol/L (150 mg/dL); (2) HDL-cholesterol <1.03 mmol/L (40 mg/dL) for men and <1.29 mmol/L (50 mg/dL) for women; (3) glucose >/=6.11 mmol/L (110 mg/dL) fasting or >/=7.77 mmol/L (140 mg/dL) nonfasting, or on treatment; (4) blood pressure > or =130/85 mm Hg or medication use, and (5) body mass index >/=25.0 kg/m(2). For both sexes, high blood pressure, high triglycerides and low HDL cholesterol were associated with increased risks of ischemic heart disease or stroke after adjustment for cardiovascular risk factors. A dose-response relationship was found between the number of metabolic risk factors and incidence of these cardiovascular end points. The multivariable hazard ratio (95% CI) associated with metabolic syndrome was 2.4 (1.4 to 4.0) in men and 2.3 (1.2 to 4.3) in women for ischemic heart disease, and 2.0 (1.3 to 3.1) and 1.5 (1.0 to 2.3), respectively, for ischemic stroke. The contribution of metabolic syndrome to the risks was independent of serum total cholesterol levels but stronger among smokers. The metabolic syndrome is a major determinant of ischemic cardiovascular disease among middle-aged Japanese men and women, in particular among smokers.


First Report of Multiple Species of the Botryosphaeriaceae Causing Bot Canker Disease of Indian Laurel-Leaf Fig in California.
Indian laurel-leaf fig (Ficus microcarpa L.) is a commonly used indoor and outdoor ornamental tree. F. microcarpa is most frequently encountered as lining city streets, especially in warmer southern California climates. A disease known as 'Sooty Canker,' caused by the fungus Nattrassia mangiferae (Syd. & P. Syd) B. Sutton & Dyko, is particularly devastating on F. microcarpa. Disease symptoms are characterized by branch dieback, crown thinning, and if the disease progresses to the trunk, eventual tree death (2). Recent taxonomic revisions have renamed Nattrassia mangiferae as Neofusicoccum mangiferae (Syd. & P. Syd.) Crous, Slippers & A. J. L. Phillips (1). An initial survey conducted during the spring of 2011 across four cities in Los Angeles County included, Culver City, Lakewood, Santa Monica, and Whittier. Five symptomatic branches per city were collected from trees showing branch cankers and dieback. Pieces of symptomatic tissue (2 mm2) were plated onto one-half-strength potato dextrose agar. Most isolates initially identified by morphological characteristics, such as growth pattern, speed of growth, and colony color, resembled those in the Botryosphaeriaceae (4). Two representative isolates from each site location were sequenced. Sequences obtained from amplification of the internal transcribed spacer region (ITS1-5.8rDNA-ITS2) and the β-tubulin gene were compared in a BLAST search in GenBank. Results identified isolates as Botryosphaeria dothidea (identity of 99% to EF638767 and 100% to JN183856.1 for ITS and β-tubulin, respectively); Neofusicoccum luteum (100% to EU650669 and 100% to HQ392752); N. mediterraneum (100% to HM443605 and 99% to GU251836); and N. parvum (100% to GU188010 and 100% to HQ392766) and have been deposited in GenBank with the following accession numbers: JN543668 to JN543671 (ITS) and JQ080549 to JQ080552 (β-tubulin). Pathogenicity tests were conducted in the greenhouse on 6-month-old F. microcarpa with one isolate from each previously listed fungal species. Five plants per isolate were stem-wound inoculated with mycelial plugs and wrapped with Parafilm. Uncolonized agar plugs were used as a control. Inoculations were later repeated a second time in the same manner for a total of 10 plants per isolate. Plants were observed for 6 weeks and destructively sampled to measure vascular lesion lengths. Mean vascular lesion lengths were 26, 22, 54, and 46 mm for B. dothidea, N. luteum, N. mediterraneum, and N. parvum, respectively. The mean lesion lengths for all isolates were significantly different (P = 0.05) from the control. Each species was consistently recovered from inoculated plants, except the control, thus fulfilling Koch's postulates. To our knowledge, this is the first report on the pathogenicity of multiple Botryosphaeriaceae species causing branch canker and dieback on F. microcarpa in California. These results are significant since trees along sidewalks in southern California are often crowded and undergo extensive root and branch pruning and some Botryosphaeriaceae spp. are known to enter its host through wounds caused by pruning or mechanical injury (2,3). Further sampling is imperative to better assess the distribution of these canker-causing fungal pathogens on F. microcarpa. References: (1) P. W. Crous et al. Stud. Mycol. 55:235, 2006. (2) D. R. Hodel et al. West. Arborist 35:28, 2009. (3) V. McDonald et al. Plant Dis. 93:967, 2009. (4) B. Slippers et al. Fungal Biol. Rev. 21:90, 2007.


Ultrasonographic and electromyographic evaluation of three types of occlusal splints on masticatory muscle activity, thickness, and length in patients with bruxism.
To evaluate occlusal splint type differences in patients with bruxism. Seventeen controls and 51 patients were divided into three subgroups, each assigned to use a different occlusal splint (hard, soft, or semi-soft) for 3 months and assessed by ultrasonography and electromyography (EMG) before (BT) and 3 months after treatment (AT). EMG values in all of the occlusal splint groups were significantly lower AT than BT (p < 0.05). BT and AT EMG values in the control group did not differ. Mean muscle thicknesses in bruxism patients was greater than in controls, and the greatest muscle thickness changes occurred with the hard occlusal splint (p < 0.05). A decrease in EMG activity occurred with all three splint types and was most prominent in the hard occlusal splint group. Ultrasonographic measurements of muscle length and thickness should be used alongside EMG to measure muscle activity in bruxism patients.


A bifunctional old yellow enzyme from Penicillium roqueforti is involved in ergot alkaloid biosynthesis.
The blue cheese-making fungus Penicillium roqueforti produces isofumigaclavine A as the main ergot alkaloid. Recently, genome mining revealed the presence of two DNA loci bearing the genetic potential for its biosynthesis. In this study, a short-chain dehydrogenase/reductase (SDR) from one of the loci was proved to be responsible for the conversion of chanoclavine-I to its aldehyde. Furthermore, a putative gene coding for an enzyme with high homology to Old Yellow Enzymes (OYEs) involved in the ergot alkaloid biosynthesis was found outside the two clusters. Biochemical characterisation of this enzyme, named FgaOx3Pr3, showed that it can indeed catalyse the formation of festuclavine in the presence of a festuclavine synthase FgaFS, as had been observed for other OYEs in ergot alkaloid biosynthesis. Differing from other homologues, FgaOx3Pr3 does not convert chanoclavine-I aldehyde to its shunt products in the absence of FgaFS. Instead, it increases significantly the product yields of several SDRs for the conversion of chanoclavine-I to its aldehyde. Kinetic studies proved that overcoming the product inhibition is responsible for the observed enhancement. To the best of our knowledge, this is the first report on the bifunctionality of an OYE and its synergistic effect with SDRs.


The bacterial flagellar cap as the rotary promoter of flagellin self-assembly.
The growth of the bacterial flagellar filament occurs at its distal end by self-assembly of flagellin transported from the cytoplasm through the narrow central channel. The cap at the growing end is essential for its growth, remaining stably attached while permitting the flagellin insertion. In order to understand the assembly mechanism, we used electron microscopy to study the structures of the cap-filament complex and isolated cap dimer. Five leg-like anchor domains of the pentameric cap flexibly adjusted their conformations to keep just one flagellin binding site open, indicating a cap rotation mechanism to promote the flagellin self-assembly. This represents one of the most dynamic movements in protein structures.


The capture proteasome assay (CAPA) to evaluate subtype-specific proteasome inhibitors.
We recently developed a new assay to measure proteasome activity in vitro (CAPA for capture proteasome assay) [1], based on proteasome capture on an antibody-coated plate. When used with lysates originating from cells expressing either standard proteasome, immunoproteasome or intermediate proteasomes β5i or β1i-β5i, this assay allows the individual monitoring of the chymotrypsin-like, trypsin-like and caspase-like activities of the corresponding proteasome subtypes. The efficiency and specificity of four proteasome inhibitors were studied using the CAPA assay, demonstrating the potential of this assay for the development of subtype-specific proteasome inhibitors.


Preserving lung after traumatic transection of left lower lobe bronchus from bullet injury.
A 22-year-old soldier was shot in the left chest by a bullet from close range. He was found to have a left haemothorax and remained shocked despite aggressive resuscitation. Due to difficult terrain and night time movement restrictions, there were limitations to the transfer of patient. So he was attended at a peripheral hospital. At emergency thoracotomy, three segmental arteries to left upper lobe were ligated and haemostasis was secured. The level of transection of left lower lobe bronchus was identified to be below the origin of the apical segmental bronchus. The lower lobe bronchus was successfully re-attached and followed up with a daily bronchoscopic clearance of distal airway. The patient made a full recovery. Anastomosis of left lower lobe bronchus after traumatic transection is a viable option for preserving an amputated lobe, in trauma settings, provided haemostatic control has been adequately achieved.


Effects of autonomous motivational priming on motivation and affective responses towards high-intensity interval training.
This study examined the effect of autonomous motivational priming on motivation, attitudes and intentions towards high-intensity interval training (HIT). Participants (N = 42) performed a graded exercise test to determine their peak aerobic power (WPEAK). At a subsequent testing session, participants were randomised to complete either an autonomous or neutral motivational priming task followed by a 10 × 1 HIT exercise protocol, alternating 1-min bouts of hard (70% WPEAK) and light (12.5% WPEAK) exercises for 20 min. Participants primed with autonomous motivation reported greater enjoyment, P = .009, ηp(2) = .16, and perceived competence, P = .005, ηp(2) = .18, post-exercise compared to those in the neutral priming condition. Participants in the autonomous motivational priming condition also reported more positive attitudes, P = .014, ηp(2) = .14, towards HIT; however, there was no difference between the conditions for task motivation during HIT or intentions, P = .53, ηp(2) = .01, to engage in HIT. These findings highlight autonomous motivational priming as a method of enhancing affective and motivational experiences regarding HIT.


Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor.
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.


Whole-Genome Sequencing of 84 Japanese Eels Reveals Evidence against Panmixia and Support for Sympatric Speciation.
The Japanese eel (Anguilla japonica), European eel (Anguilla anguilla), and American eel (Anguilla rostrata) are migratory, catadromous, temperate zone fish sharing several common life cycle features. The population genetics of panmixia in these eel species has already been investigated. Our extensive population genetics analysis was based on 1400 Gb of whole-genome sequence (WGS) data from 84 eels. It demonstrated that a Japanese eel group from the Kuma River differed from other populations of the same species. Even after removing the potential adapted/selected single nucleotide polymorphism (SNP) data, and with very small differences (fixation index [Fst] = 0.01), we obtained results consistently indicating that panmixia does not occur in Japanese eels. The life cycle of the Japanese eel is well-established and the Kuma River is in the center of its habitat. Nevertheless, simple reproductive isolation is not the probable cause of non-panmixia in this species. We propose that the combination of spawning area subdivision, philopatry, and habitat preference/avoidance accounts for the non-panmixia in the Japanese eel population. We named this hypothesis the "reproductive isolation like subset mapping" (RISM) model. This finding may be indicative of the initial stages of sympatric speciation in these eels.


Coupled 142Nd-143Nd isotopic evidence for Hadean mantle dynamics.
The oldest rocks-3.85 billion years old-from southwest Greenland have coupled neodymium-142 excesses (from decay of now-extinct samarium-146; half-life, 103 million years) and neodymium-143 excesses (from decay of samarium-147; half-life, 106 billion years), relative to chondritic meteorites, that directly date the formation of chemically distinct silicate reservoirs in the first 30 million to 75 million years of Earth history. The differences in 142Nd signatures of coeval rocks from the two most extensive crustal relicts more than 3.6 billion years old, in Western Australia and southwest Greenland, reveal early-formed large-scale chemical heterogeneities in Earth's mantle that persisted for at least the first billion years of Earth history. Temporal variations in 142Nd signatures track the subsequent incomplete remixing of very-early-formed mantle chemical domains.


Childhood maltreatment and the medical morbidity in bipolar disorder: a case-control study.
Childhood maltreatment (abuse and neglect) can have long-term deleterious consequences, including increased risk for medical and psychiatric illnesses, such as bipolar disorder in adulthood. Emerging evidence suggests that a history of childhood maltreatment is linked to the comorbidity between medical illnesses and mood disorders. However, existing studies on bipolar disorder have not yet explored the specific influence of child neglect and have not included comparisons with individuals without mood disorders (controls). This study aimed to extend the existing literature by examining the differential influence of child abuse and child neglect on medical morbidity in a sample of bipolar cases and controls. The study included 72 participants with bipolar disorder and 354 psychiatrically healthy controls (average age of both groups was 48 years), who completed the Childhood Trauma Questionnaire, and were interviewed regarding various medical disorders. A history of any type of childhood maltreatment was significantly associated with a diagnosis of any medical illness (adjusted OR = 6.28, 95% confidence intervals 1.70-23.12, p = 0.006) and an increased number of medical illnesses (adjusted OR = 3.77, 95% confidence intervals 1.34-10.57, p = 0.012) among adults with bipolar disorder. Exposure to child abuse was more strongly associated with medical disorders than child neglect. No association between childhood maltreatment and medical morbidity was detected among controls. To summarise, individuals with bipolar disorder who reported experiencing maltreatment during childhood, especially abuse, were at increased risk of suffering from medical illnesses and warrant greater clinical attention.


Comparative ultrasound measurement of normal thyroid gland dimensions in school aged children in our local environment.
The objective of this study was to determine the measurement of normal range of ultrasound (US) thyroid gland dimensions in school-aged children (6-16 years) in our environment and compared with what is obtained elsewhere. A prospective ultrasound measurement study done in University of Benin Teaching Hospital Benin, Nigeria. A prospective ultrasound (US) study of thyroid dimensions of 500 school-aged children in our environment consisting of 227 boys and 273 girls was done from 1 December 2006 to July 2007. The subjects were examined by the authors and subjects with palpable abnormal thyroid gland were excluded from the study. The thyroid dimensions (length, height, and diameter) were taken for each lobe by means of ultrasound (US). In addition volume of each thyroid lobe was calculated and the summation of volume of the lobes was taken as thyroid gland volume of each subject. Also height and weight of patients were documented from which the subject's body surface was calculated. Incidental thyroid gland lesion in US was excluded from the study. Using the Statistical program of social science (SPSS) and INSTAT (Graph Pad Inc. USA) the data were analyzed. Informed consent was obtained from all the subjects and the study was done in line with the ethical guidelines of the centers. The US thyroid gland volume in school-aged children in Benin City from this study ranges between 1.17 cm 3 and 7.19 cm 3 , mean volume range of 1.76-4.95 cm 3 , median volume range of 1.73-4.73 cm 3 , and range of standard deviation from 0.39 cm 3 to 1.49 cm 3 . The average mean thyroid volume is 2.32 cm 3 with the following average dimensions; anteroposterior right lobe =1.06 cm, mediolateral right lobe = 1.01 cm and craniocaudal right lobe = 2.34 cm, and anteroposterior left lobe = 1.01 cm, mediolateral left lobe = 1.04 cm and craniocaudal left lobe = 2.41 cm for both boys and girls respectively. These data are significantly lower than data obtained by European based World Health Organization/International Council for the Control of Iodine Deficiency Disorders (WHO/ICCIDD) 1997. However there is significant similarity with data obtained in similar environment. Ultrasound thyroid gland dimensions in school-aged children in our environment are reproducible and the data obtained are comparable to those obtained in other environment. The values may be better used in our environment as reference data for screening purposes.


Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos.
Mouse embryos were exposed to maternally administered RA on day 8.0 or day 7 3/4 of development, i.e. at or just before the differentiation of the cranial neural plate, and before the start of segmentation. On day 9.0, the RA-treated embryos had a shorter preotic hindbrain than the controls and clear rhombomeric segmentation was absent. These morphological effects were correlated with alterations in the spatiotemporal distribution patterns of two genes, Hox-2.9 and Krox-20, which are expressed in the otic and preotic hindbrain and in specific neural crest cell populations. Hox-2.9 was expressed throughout the preotic hindbrain region, instead of being confined to rhombomere 4. Krox-20 was not expressed rostral to the Hox-2.9 domain, i.e. its normal rhombomere 3 domain was absent. The Hox-2.9/Krox-20 boundary was ill-defined, with patches of alternating expression of the two genes. In migrating neural crest cells, Hox-2.9 expression was both abnormally extensive and abnormally prolonged. Neural crest cells expressing Krox-20 remained close to the neural tube. Embryos exposed to RA on day 8 1/4 appeared to be morphologically normal. We suggest that early events leading to rhombomeric segmentation and rhombomere-specific gene expression are specifically vulnerable to raised RA levels, and may require RA levels lower than those in the region of somitic segmentation.


A soft body as a reservoir: case studies in a dynamic model of octopus-inspired soft robotic arm.
The behaviors of the animals or embodied agents are characterized by the dynamic coupling between the brain, the body, and the environment. This implies that control, which is conventionally thought to be handled by the brain or a controller, can partially be outsourced to the physical body and the interaction with the environment. This idea has been demonstrated in a number of recently constructed robots, in particular from the field of "soft robotics". Soft robots are made of a soft material introducing high-dimensionality, non-linearity, and elasticity, which often makes the robots difficult to control. Biological systems such as the octopus are mastering their complex bodies in highly sophisticated manners by capitalizing on their body dynamics. We will demonstrate that the structure of the octopus arm cannot only be exploited for generating behavior but also, in a sense, as a computational resource. By using a soft robotic arm inspired by the octopus we show in a number of experiments how control is partially incorporated into the physical arm's dynamics and how the arm's dynamics can be exploited to approximate non-linear dynamical systems and embed non-linear limit cycles. Future application scenarios as well as the implications of the results for the octopus biology are also discussed.


Dignity and informed consent in the treatment of mature minors.
In today's world, as evinced in various human rights provisions, emphasis is placed on the assertion and protection of the entrenched rights of every human and particularly the dignity of humans and respect of human autonomy. Medical/health workers are concerned about protecting every patient's right to the dignity of his or her person. This led to the formulation of the concept of self determination and informed consent in medical diagnosis and treatments. However, serious concern is placed on these principles especially as it affects mature minors, a group of individuals who by conduct demand a level of respect but may at the same time be viewed as not capable of making the "best" informed decisions, especially about health. The following issues may arise as a result of the aforementioned concerns: --are mature young ones entitled to right of self determination and informed consent despite the alleged fear that they may lack capacity to make informed decisions? --if no, who should decide on their behalf--their parents, their medical/health provider or the society/government (especially since the 3 (three) interested groups may have different and conflicting stands on what is best for the child); --if the answer to the initial question is yes, to what extent should mature minors be informed of their medical choices and be allowed to exercise their right of self determination? --should they be guided? --and who should so guide them? In resolving the above issue, due consideration has been given not only to legal and bio-ethical provisions of some countries but also to international conventions which several countries are party to. Thereafter, it became clear that most authorities are of the view that mature minors should be fully informed and be allowed to have a say in health decisions, coaching them with few exceptions. Ultimately, because of the importance of respect for human dignity, autonomy and self determination along with medical disclosure in today's world, it will be recommended that laws in a number of jurisdictions need to be reviewed to reflect the current international trend and amended or replaced as the need might be.


Effects of pancreas transplantation on postprandial glucose metabolism.
Because a pancreas allograft is placed in the pelvis, pancreas transplantation abolishes the normal gradient between portal-vein and peripheral-vein insulin concentrations and causes systemic hyperinsulinemia. Whether pancreas transplantation restores carbohydrate metabolism to normal is not known. We studied seven patients with insulin-dependent diabetes mellitus after pancreas-kidney transplantation, seven nondiabetic patients after kidney transplantation (to control for immunosuppression), and eight normal subjects. Measurements were made after an overnight fast and after ingestion of a mixed meal. Although plasma glucose concentrations did not differ in the two transplant groups, plasma insulin concentrations were significantly higher in the diabetic pancreas-kidney recipients than in the nondiabetic kidney recipients, both before the meal (mean +/- SE, 102 +/- 15 vs. 53 +/- 6 pmol per liter; P less than 0.05) and afterward (123 +/- 22 vs. 61 +/- 6 nmol per liter per six hours; P less than 0.05). Plasma C-peptide concentrations were the same in both groups, indicating that hyperinsulinemia was due to decreased insulin clearance rather than increased insulin secretion. Despite drainage of the venous effluent from the transplanted pancreas into the systemic circulation, the values for splanchnic clearance of ingested glucose, suppression of hepatic glucose release, incorporation of carbon dioxide into glucose, stimulation of glucose oxidation, glucose uptake, and forearm glucose clearance were all similar in the transplant groups and differed minimally from the values in the normal group. The similar rates of glucose uptake in the presence of higher systemic insulin concentrations indicated that the extrahepatic tissues of the diabetic pancreas-kidney recipients were insulin-resistant. Despite systemic delivery of insulin, pancreas-kidney transplantation in patients with diabetes results in carbohydrate metabolism similar to that in nondiabetic subjects receiving the same immunosuppressive agents after kidney transplantation.


Brain and kidney, victims of atrial microembolism in elderly hospitalized patients? Data from the REPOSI study.
It is well known that atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with a higher risk of stroke, and new evidence links AF to cognitive impairment, independently from an overt stroke (CI). Our aim was to investigate, assuming an underlying role of atrial microembolism, the impact of CI and CKD in elderly hospitalized patients with AF. We retrospectively analyzed the data collected on elderly patients in 66 Italian hospitals, in the frame of the REPOSI project. We analyzed the clinical characteristics of patients with AF and different degrees of CI. Multivariate logistic analysis was used to explore the relationship between variables and mortality. Among the 1384 patients enrolled, 321 had AF. Patients with AF were older, had worse CI and disability and higher rates of stroke, hypertension, heart failure, and CKD, and less than 50% were on anticoagulant therapy. Among patients with AF, those with worse CI and those with lower estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds ratio 1.13, p=0.006). Higher disability levels, older age, higher systolic blood pressure, and higher eGFR were related to lower probability of oral anticoagulant prescription. Lower mortality rates were found in patients on oral anticoagulant therapy. Elderly hospitalized patients with AF are more likely affected by CI and CKD, two conditions that expose them to a higher mortality risk. Oral anticoagulant therapy, still underused and not optimally enforced, may afford protection from thromboembolic episodes that probably concur to the high mortality.


DaReUS-Loop: accurate loop modeling using fragments from remote or unrelated proteins.
Despite efforts during the past decades, loop modeling remains a difficult part of protein structure modeling. Several approaches have been developed in the framework of crystal structures. However, for homology models, the modeling of loops is still far from being solved. We propose DaReUS-Loop, a data-based approach that identifies loop candidates mining the complete set of experimental structures available in the Protein Data Bank. Candidate filtering relies on local conformation profile-profile comparison, together with physico-chemical scoring. Applied to three different template-based test sets, DaReUS-Loop shows significant increase in the number of high-accuracy loops, and significant enhancement for modeling long loops. A special advantage is that our method proposes a prediction confidence score that correlates well with the expected accuracy of the loops. Strikingly, over 50% of successful loop models are derived from unrelated proteins, indicating that fragments under similar constraints tend to adopt similar structure, beyond mere homology.


Subthalamic nucleus gamma oscillations mediate a switch from automatic to controlled processing: a study of random number generation in Parkinson's disease.
In paced random number generation (RNG) participants are asked to generate numbers between 1 and 9 in a random fashion, in synchrony with a pacing stimulus. Successful task performance can be achieved through control of the main biases known to exist in human RNG compared to a computer generated series: seriation, cycling through a set of available numbers, and repetition avoidance. A role in response inhibition and switching from automatic to controlled processing has previously been ascribed to the subthalamic nucleus (STN). We sought evidence of frequency-specific changes in STN oscillatory activity which could be directly related to use of such strategies during RNG. Local field potentials (LFPs) were recorded from depth electrodes implanted in the STN of 7 patients (14 sides) with Parkinson's disease (PD), when patients were on dopaminergic medication. Patients were instructed to (1) generate a series of 100 numbers between 1 and 9 in a random fashion, and (2) undertake a control serial counting task, both in synchrony with a 0.5 Hz pacing stimulus. Significant increases in LFP power (p ≤ 0.05) across a narrow gamma frequency band (45-60 Hz) during RNG, compared to the control counting task, were observed. Further, the number of 'repeated pairs' (a decline in which reflects repetition avoidance bias in human RNG) was positively correlated with these gamma increases. We therefore suggest that STN gamma activity is relevant for controlled processing, in particular the active selection and repetition of the same number on successive trials. These results are consistent with a frequency-specific role of the STN in executive processes such as suppression of habitual responses and 'switching-on' of more controlled processing strategies.


[Rational estimation of drug dosage through pharmacometric modeling: The case of a long-acting depot antipsychotic].
Drug manufacturer seeking authorization to bring a newly medicinal compound to the market (Market Authorization Application) have to undertake various studies, each of them providing a specific report. It is however essential to know how to pool results in order to understand the behavior of the drug in all the situations likely to be encountered in clinical practice. The exploitation of these data is now carried out through pharmacometric analyzes which aim at quantifying the exposure and the response of a drug over time. These methods (named "population approach") are based on non-linear mixed effects model and therefore, on the identification of a mathematical model. A first step is to model the variations in concentrations over time by integrating the physio-pathological characteristics of the patients. At this stage, the Bayesian analysis is essential to identify and select the factors of interindividual variability. This pharmacokinetic (PK) modeling allows us to obtain the prescribed dose for each patient, but also their exposure. The second step consists in defining the relationship between exposure and effect: pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors' occupancy rate or the evolution of a clinical score (BPRS, PANSS…) over time. The final PK-PD model defines the target exposure, that is to say, the concentration values required to achieve maximum effect on the score studied without risking over-exposure. Ultimately, a Monte Carlo simulation will be conducted which will test the expected response for different doses and will facilitate a rational choice in dosage. Assessing the process behind the transition from an oral to a long-acting injectable form of an active ingredient such as aripiprazole can be done by following the same protocol. A 10- to 30-mg per day therapeutic range has thus been identified. The model incorporates all the identified factors of variability of aripiprazole (drug interactions and genetic polymorphism of the P450 2D6 cytochrome) and showed that with an injectable sustained release form, a monthly dose of 400mg would allow 90% of patients to gain exposure in the therapeutic range. In case of a drug inhibition and/or of a slow metabolizing profile, dosage adjustment is necessary.


Protecting Children From Tobacco, Nicotine, and Tobacco Smoke.
This technical report serves to provide the evidence base for the American Academy of Pediatrics' policy statements "Clinical Practice Policy to Protect Children From Tobacco, Nicotine, and Tobacco Smoke" and "Public Policy to Protect Children From Tobacco, Nicotine, and Tobacco Smoke." Tobacco use and involuntary exposure are major preventable causes of morbidity and premature mortality in adults and children. Tobacco dependence almost always starts in childhood or adolescence. Electronic nicotine delivery systems are rapidly gaining popularity among youth, and their significant harms are being documented. In utero tobacco smoke exposure, in addition to increasing the risk of preterm birth, low birth weight, stillbirth, placental abruption, and sudden infant death, has been found to increase the risk of obesity and neurodevelopmental disorders. Actions by pediatricians can help to reduce children's risk of developing tobacco dependence and reduce children's involuntary tobacco smoke exposure. Public policy actions to protect children from tobacco are essential to reduce the toll that the tobacco epidemic takes on our children.


Integrative Medicine: Cannabis and Cannabis-Related Drugs.
Cannabis is a genus of flowering herbs in the Cannabaceae family. Federal law defines dried plant material preparations of the subspecies Cannabis sativa as marijuana. The term cannabis refers to all products derived from Cannabis plants. The active compounds in cannabis are cannabinoids, which include delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive component, whereas CBD has no psychoactive effects. There are three Food and Drug Administration (FDA)-approved cannabis-related drugs. Dronabinol and nabilone (Cesamet) are approved for chemotherapy-induced nausea and vomiting; cannabidiol (Epidiolex) is approved for two pediatric epilepsy syndromes. FDA-approved cannabis-related drugs, marijuana, and cannabis formulations have been studied for the management of other conditions and symptoms (eg, cachexia, chemotherapy-induced nausea and vomiting, chronic pain, muscle spasticity) and have shown varying effectiveness. CBD formulations have been shown to be effective for certain forms of epilepsy. However, marijuana, cannabis-containing products, and cannabis-derived products in general are not approved by the FDA for any indication. Adverse effects include impaired executive function, cognition, and driving. Physicians can recommend use of marijuana under medical marijuana laws but cannot prescribe it, as it is classified as a Schedule I controlled substance. Laws regulating use of marijuana and cannabis products vary among states.


The neurological basis of conscious color perception in a blind patient.
We have studied patient PB, who, after an electric shock that led to vascular insufficiency, became virtually blind, although he retained a capacity to see colors consciously. For our psychophysical studies, we used a simplified version of the Land experiments [Land, E. (1974) Proc. R. Inst. G. B. 47, 23-58] to learn whether color constancy mechanisms are intact in him, which amounts to learning whether he can assign a constant color to a surface in spite of changes in the precise wavelength composition of the light reflected from that surface. We supplemented our psychophysical studies with imaging ones, using functional magnetic resonance, to learn something about the location of areas that are active in his brain when he perceives colors. The psychophysical results suggested that color constancy mechanisms are severely defective in PB and that his color vision is wavelength-based. The imaging results showed that, when he viewed and recognized colors, significant increases in activity were restricted mainly to V1-V2. We conclude that a partly defective color system operating on its own in a severely damaged brain is able to mediate a conscious experience of color in the virtually total absence of other visual abilities.


Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort.
Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD. A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations. Associations of eight a priori GWAS SNPs with BD were replicated with nominal (P≤.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction. These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD.


Electronic healthcare databases for active drug safety surveillance: is there enough leverage?
To provide estimates of the number and types of drugs that can be monitored for safety surveillance using electronic healthcare databases. Using data from eight European databases (administrative claims, medical records) and in the context of a cohort study, we determined the amount of drug exposure required for signal detection across varying magnitudes of relative risk (RR). We provide estimates of the number and types of drugs that can be monitored as a function of actual use, minimal detectable RR, and empirically derived incidence rates for the following adverse events: (i) acute myocardial infarction; (ii) acute renal failure; (iii) anaphylactic shock; (iv) bullous eruptions; (v) rhabdomyolysis; and (vi) upper gastrointestinal bleeding. We performed data simulation to see how expansion of database size would influence the capabilities of such system. Data from 1,947,452 individuals (59,594,132 person-years follow-up) who used 2,289 drugs in the EU-ADR network show that for a frequent event such as acute myocardial infarction, there are 531 drugs (23% of total) for which an association with RR = 2, if present, can be investigated. For a rare event such as rhabdomyolysis, there are 19 drugs (1%) for which an association of same magnitude can be investigated. Active surveillance using healthcare data-based networks for signal detection is feasible, although the leverage to do so may be low for infrequently used drugs and for rare outcomes. Extending database network size to include data from heterogeneous populations and increasing follow-up time are warranted to maximize leverage of these surveillance systems.


The role of potassium in the metabolic control of coronary vascular resistance of the dog.
We tested the hypothesis that potassium ion (K+) is involved in the local control of the coronary circulation. The left coronary artery was perfused at constant flow in closed-chest, anesthetized dogs. Step increases in heart rate caused transient (six dogs) or sustained (three dogs) increases in coronary sinus plasma [K+] averaging 0.53 mEq/liter. When the effects of vascular transit delay were accounted for, we found that [K+] changes preceded the vasodilation seen with increased heart rate. We used a mathematical model to calculate changes in interstitial [K+] from arterial and venous [K+] and K+ release rate. The magnitude of the changes in interstitial [K+] appeared to be sufficient to account for a considerable portion but not all of the initial changes in coronary vascular resistance associated with increased heart rate. Thus potassium seems to be involved at least transiently, and, in three of nine dogs, for a more sustained period, in heart rate-induced coronary vasodilation. Cessations (for 15 seconds) of coronary blood flow resulted in transient postischemic increases of coronary sinus [K+] averaging 0.55 mEq/liter. In this case, correction for vascular transit disclosed that the recovery of [K+] preceded the return of vascular tone to baseline for only the second half of the recovery, implying only a limited role for potassium in this response. Potassium appears to play a significant but transient role in the local control of the coronary circulation.


Defining Nonmedical Use of Prescription Opioids Within Health Care Claims: A Systematic Review.
Health insurance claims data may play an important role for health care systems and payers in monitoring the nonmedical use of prescription opioids (NMPO) among patients. However, these systems require valid methods for identifying NMPO if they are to target individuals for intervention. Limited efforts have been made to define NMPO using administrative data available to health systems and payers. We conducted a systematic review of publications that defined and measured NMPO within health insurance claims databases in order to describe definitions of NMPO and identify areas for improvement. We searched 8 electronic databases for articles that included terms related to NMPO and health insurance claims. A total of 2613 articles were identified in our search. Titles, abstracts, and article full texts were assessed according to predetermined inclusion/exclusion criteria. Following article selection, we extracted general information, conceptual and operational definitions of NMPO, methods used to validate operational definitions of NMPO, and rates of NMPO. A total of 7 studies met all inclusion criteria. A range of conceptual NMPO definitions emerged, from concrete concepts of abuse to qualified definitions of probable misuse. Operational definitions also varied, ranging from variables that rely on diagnostic codes to those that rely on opioid dosage and/or filling patterns. Quantitative validation of NMPO definitions was reported in 3 studies (e.g., receiver operating curves or logistic regression), with each study indicating adequate validity. Three studies reported qualitative validation, using face and content validity. One study reported no validation efforts. Rates of NMPO among the studies' populations ranged from 0.75% to 10.32%. Disparate definitions of NMPO emerged from the literature, with little uniformity in conceptualization and operationalization. Validation approaches were also limited, and rates of NMPO varied across studies. Future research should prospectively test and validate a construct of NMPO to disseminate to payers and health officials.


HIV infection among persons who inject drugs: ending old epidemics and addressing new outbreaks.
AIDS among persons who inject drugs, first identified in December 1981, has become a global epidemic. Injecting drug use has been reported in 148 countries and HIV infection has been seen among persons who inject drugs in 61 countries. Many locations have experienced outbreaks of HIV infection among persons who inject drugs, under specific conditions that promote very rapid spread of the virus. In response to these HIV outbreaks, specific interventions for persons who inject drugs include needle/syringe exchange programs, medicated-assisted treatment (with methadone or buprenorphine) and antiretroviral therapy. Through a 'combined prevention' approach, these interventions significantly reduced new HIV infections among persons who inject drugs in several locations including New York City, Vancouver and France. The efforts effectively ended the HIV epidemic among persons who inject drugs in those locations. This review examines possible processes through which combined prevention programs may lead to ending HIV epidemics. However, notable outbreaks of HIV among persons who inject drugs have recently occurred in several countries, including in Athens, Greece; Tel-Aviv, Israel; Dublin, Ireland; as well as in Scott County, Indiana, USA. This review also considers different factors that may have led to these outbreaks. We conclude with addressing the remaining challenges for reducing HIV infection among persons who inject drugs.


Reducing the diffraction artifacts while implementing a phase function on a spatial light modulator.
Spatial light modulators are often used to implement phase modulation. Since they are pixelated, the phase function is usually approximated by a regularly sampled piecewise constant function, and the periodicity of the pixel sampling generates annoying diffraction peaks. We theoretically investigate two pixelation techniques: the isophase method and a new nonperiodic method derived from the Voronoi tessellation technique. We show that, for a suitable choice of parameters, the diffraction peaks disappear and are replaced by a smoothly varying halo. We illustrate the potential of these two techniques for implementing a lens function and wavefront correction.


Combining pest control and resistance management: synergy of engineered insects with Bt crops.
Transgenic crops producing insecticidal toxins are widely used to control insect pests. Their benefits would be lost if resistance to the toxins became widespread in pest populations. The most widely used resistance management method is the high-dose/refuge strategy. This requires toxin-free host plants as refuges near insecticidal crops, and toxin doses intended to be sufficiently high to kill insects heterozygous for a resistant allele, thereby rendering resistance functionally recessive. We have previously shown by mathematical modeling that mass-release of harmless susceptible (toxin-sensitive) insects engineered with repressible female-specific lethality using release of insects carrying a dominant lethal ([RIDL] Oxitec Limited, United Kingdom) technology could substantially delay or reverse the spread of resistance and reduce refuge sizes. Here, we explore this proposal in depth, studying a wide range of scenarios, considering impacts on population dynamics as well as evolution of allele frequencies, comparing with releases of natural fertile susceptible insects, and examining the effect of seasonality. We investigate the outcome for pest control for which the plant-incorporated toxins are not necessarily at a high dose (i.e., they might not kill all homozygous susceptible and all heterozygous insects). We demonstrate that a RIDL-based approach could form an effective component of a resistance management strategy in a wide range of genetic and ecological circumstances. Because there are significant threshold effects for several variables, we expect that a margin of error would be advisable in setting release ratios and refuge sizes, especially as the frequency and properties of resistant alleles may be difficult to measure accurately in the field.


Measuring Care-Related Quality of Life of Caregivers for Use in Economic Evaluations: CarerQol Tariffs for Australia, Germany, Sweden, UK, and US.
Informal care is often not included in economic evaluations in healthcare, while the impact of caregiving can be relevant for cost-effectiveness recommendations from a societal perspective. The impact of informal care can be measured and valued with the CarerQol instrument, which measures the impact of informal care on seven important burden dimensions (CarerQol-7D) and values this in terms of general quality of life (CarerQol-VAS). The CarerQol can be included at the effect side of multi-criteria analyses of patient interventions or in cost-effectiveness or utility analysis of interventions targeted at caregivers. At present, utility scores based on relative utility weights for the CarerQol-7D are only available for the Netherlands. This study calculates CarerQol-7D tariffs for Australia, Germany, Sweden, UK, and US. Data were collected among the general population in Australia, Germany, Sweden, UK, and US by an Internet survey. Utility weights were collected with a discrete choice experiment with two unlabeled alternatives described in terms of the seven CarerQol-7D dimensions. An efficient experimental design with priors obtained from the Netherlands was used to create the choice sets. Data was analyzed with a panel mixed multinomial logit model with random parameters. In all five countries, the CarerQol-7D dimensions were significantly associated with the utility of informal care situations. Physical health problems were most strongly associated with the utility for informal care situations. The tariff was constructed by adding up the relative utility weights per category of all CarerQol-7D dimensions for each country separately. The CarerQol tariffs for Australia, Germany, Sweden, UK, and US facilitate the inclusion of informal care in economic evaluations.


Dual roles of an algal farming damselfish as a cultivator and opportunistic browser of an invasive seaweed.
Herbivory is a fundamental process determining reef resilience, and while algal farming damselfishes can help shape benthic assemblages, an understanding of their contribution to areas outside of defended territories is relatively unexplored. Here, we demonstrate how the farming damselfish Stegastes marginatus plays a dual role in benthic structuring by 1) contributing to persistence of the invasive macroalga Acanthophora spicifera within a Hawaiian marine protected area, where the macroalga occurred exclusively inside Stegastes territories, and 2) behaving as an opportunistic browser of the exotic alga outside their territorial borders. Greater than 50% of the biomass of tethered A. spicifera was consumed within one-hour when placed outside Stegastes territories, compared to <5% lost from tethers within territories or herbivore exclusion cages. In situ remote video revealed that tethered A. spicifera located outside territories was grazed primarily by the surgeonfish Acanthurus nigrofuscus (∼68% of total bites) and, surprisingly, by S. marginatus (∼27% of total bites) that left their territories to feed on this resource on 107 occasions during 400 min of filming. Further, for over half of those occurrences where S. marginatus grazed on the tethered macroalga outside of territories, they fed alongside conspecifics and other species, displaying little of the aggressiveness that characterizes this damselfish. These results show that S. marginatus plays a wider role in determining benthic assemblages than previously recognized, acting both as cultivators of a canopy-forming invasive macroalga within their territories, and as opportunistic browsers in neighboring sites. Consequently, S. marginatus can affect benthic species composition across their territory borders. These results provide a rare example of interspecific facilitation of an exotic alga by an indigenous marine fish. Accounting for fish behaviors more broadly is important to further our understanding of ecological processes that shape reef ecosystems to improve management of MPAs that often support extensive farming damselfish populations.


Functional properties of muscarinic receptor subtypes Hm1, Hm3 and Hm5 expressed in Sf9 cells using the baculovirus expression system.
The human muscarinic ACh receptor subtypes m1, m3 and m5 have been expressed in Sf9 cells using the baculovirus expression system. Stimulation of all three subtypes with CCh caused an increase in inositol-1,4,5-trisphosphate and intracellular Ca++. The increase in cytosolic free Ca++ was to a large extent due to influx. The levels of receptors (< 0.1-1 pmol/mg protein) increased with infection time in a narrow time span (24-36 h). The changes in the receptor densities did not significantly affect the EC50 values of CCh-mediated Ca++ mobilization with the m3 or the m5 subtype. The EC50 value was higher with the m1 receptor at low expression levels (approximately 100 fmol/mg protein), and it decreased with an increase in receptor density. The receptor subtypes displayed no gross differences in their response to oxotremorine-M, which behaved as a full agonist, or to oxotremorine and pilocarpine, which were less active. With the m3 subtype, there was an increase in the maximal response to oxotremorine with longer infection times. The results demonstrate that the recombinant muscarinic receptors, expressed in Sf9 cells, show many of the characteristics of endogenously expressed receptors when studied at low expression levels and that the receptor density may significantly affect the receptor pharmacology.


CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer.
Chronic inflammation is a well-known risk factor for cancer. Proinflammatory mediators such as prostaglandin E2 (PGE2) promote colorectal tumor growth by stimulating angiogenesis, cell invasion, and cell growth, and inhibiting apoptosis. Molecules that regulate tumor-associated angiogenesis provide promising therapeutic targets for treatment of colorectal cancer (CRC) as indicated by the recent development of the novel anti-angiogenic agent bevacizumab (Avastin). However, use of this drug only prolongs survival by several months, highlighting the importance of finding more effective treatment regimens. We report here that PGE2 induces expression of CXCL1 (growth-regulated oncogene alpha), a pro-angiogenic chemokine, in human CRC cells. More importantly, CXCL1 released from carcinoma cells induces microvascular endothelial cell migration and tube formation in vitro. Furthermore, PGE2 promotes tumor growth in vivo by induction of CXCL1 expression, which results in increased tumor microvessel formation. These results have potential clinical significance because we found that CXCL1 expression correlates with PGE2 levels in human CRCs. Collectively, our findings show for the first time that CXCL1 is regulated by PGE2 and indicate that CXCL1 inhibitors should be evaluated further as potential anti-angiogenic agents for treatment of CRC.


Postoperative hypoxia is a contributory factor to cognitive impairment after cardiac surgery.
Cognitive dysfunction and postoperative hypoxia are common sequelae of coronary artery bypass grafting, but there has been no study to determine whether there is any relationship between them. Arterial blood gas measurements were performed before surgical intervention and on the second and fifth postoperative day, and neuropsychological assessments were performed before surgical intervention and 5 days and 3 months postoperatively by using a battery of 10 psychometric tests in 175 patients undergoing coronary artery bypass grafting. An estimate of overall performance on the battery at each assessment point was provided by a simple aggregate cognitive index score calculated from the mean z scores of 4 normally distributed test variables. Multiple regression analysis was performed by using the cognitive index score at day 5 as the dependent variable, with age, sex, duration of the operation, presence or absence of cardiopulmonary bypass, preoperative cognitive index score, and arterial oxygenation and percentage of saturation at day 5 as independent variables. The mean cognitive index score decreased significantly in 115 (66%) patients who agreed to neuropsychological test battery assessment on the fifth postoperative day but improved significantly beyond baseline at 3 months. Mean arterial oxygen tension and percentage of saturation decreased significantly 2 days after the operation and, although improving over the following 3 days, remained decreased at day 5. Decreased cognitive index scores at day 5 strongly predicted cognitive impairment at 3 months (r = 0.36). The only significant independent predictors of the day 5 cognitive index score in the multiple regression analysis were preoperative cognitive index score and arterial oxygenation tension at day 5 (r = 0.24, P <.03). We report a significant correlation between postoperative cognitive dysfunction and hypoxia 5 days after coronary artery bypass grafting. This finding might have therapeutic implications because early postoperative cognitive dysfunction influences long-term impairment.


Nurses' attitudes about the importance of families in nursing care: a survey of Swedish nurses.
The purpose of this study was to investigate the attitudes of registered nurses (RNs) about the importance of involving families in nursing care. A sample of 634 randomly selected Swedish RNs completed the instrument, Families' Importance in Nursing Care-Nurses' Attitudes (FINC-NA), and reported holding supportive attitudes about families. High scores were found for the subscales: family as a resource in nursing care, family as a conversational partner, family as a burden, and family as its own resource. Variables that predicted a less supportive attitude about involving families in nursing care included being a newly graduated nurse, having no general approach to the care of families at the place of work, and being a male nurse.


Relationship between gender and survival in a real-life cohort of patients with COPD.
Although COPD affects both men and women, its prevalence is increasing more rapidly in women. Disease outcomes appear different among women with more frequent dyspnea and anxiety or depression but whether this translates into a different prognosis remains to be determined. Our aim was to assess whether the greater clinical impact of COPD in women was associated with differences in 3-year mortality rates. In the French Initiatives BPCO real-world cohort, 177 women were matched up to 458 menon age (within 5-year intervals) and FEV1 (within 5% predicted intervals). 3-year mortality rate and survival were analyzed. Univariate and multivariate logistic regression analyses were performed. For a given age and level of airflow obstruction, women with COPD had more severe dyspnea, lower BMI, and were more likely to exhibit anxiety. Nevertheless, three-year mortality rate was comparable among men and women, respectively 11.2 and 10.8%. In a multivariate model, the only factors significantly associated with mortality were dyspnea and malnutrition but not gender. Although women with COPD experience higher levels of dyspnea and anxiety than men at comparable levels of age and FEV1, these differences do not translate into variations in 3-year mortality rates. 04-479.


Esophageal and Gastric Cancer Pearl: a nationwide clinical biobanking project in the Netherlands.
Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer.


Epidermal growth factor receptor T790M mutation: A major culprit in the progression of epidermal growth factor receptor-driven non-small cell lung cancer and the role of repeat biopsy.
Non-small cell lung cancer (NSCLC) accounts for the majority of primary lung cancer cases worldwide. The activating mutations of epidermal growth factor receptor (EGFR) have been demonstrated to associate with the development of NSCLC, with T790M mutation being the most common. Over the years, EGFR tyrosine kinase inhibitors (TKIs) were developed to target EGFR-related mutations. However, patients with activating EGFR mutations who are initially responsive to EGFR-TKIs eventually develop acquired resistance after a median progression-free survival of 10-16 months, followed by disease progression. Recently, the third-generation EGFR inhibitors have emerged as potential therapeutics to block the growth of EGFR T790M-positive tumors. This article reviews the emerging data regarding EGFR mutations and clinical evidence on third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC. It also reviews the role of repeat biopsy in improving the success rates of treatment of EGFR T790M-derived drug-resistant NSCLC.


Internal control beliefs shape positive affect and associated neural dynamics during outcome valuation.
Experiencing events as controllable is essential for human well-being. Based on classic psychological theory, we test how internal control beliefs impact the affective valuation of task outcomes, neural dynamics and ensuing behavioral preferences. In three consecutive studies we show that dynamics in positive affect increase, with a qualitative shift towards self-evaluative pride, when agents believe they caused a given outcome. We demonstrate that these outcomes engage brain networks processing self-referential information in the cortical midline. Here, activity in the ventromedial prefrontal cortex tracks outcome valence regarding both success as well as internal control, and covaries with positive affect in response to outcomes. These affective dynamics also relate to increased functional coupling between the ventral striatum and cortical midline structures. Finally, we show that pride predicts preferences for control, even at monetary costs. Our investigations extend recent models of positive affect and well-being, and emphasize that control beliefs drive intrinsic motivation.


Evaluating the effectiveness, impact and safety of live attenuated and seasonal inactivated influenza vaccination: protocol for the Seasonal Influenza Vaccination Effectiveness II (SIVE II) study.
Seasonal (inactivated) influenza vaccination is recommended for all individuals aged 65+ and in individuals under 65 who are at an increased risk of complications of influenza infection, for example, people with asthma. Live attenuated influenza vaccine (LAIV) was recommended for children as they are thought to be responsible for much of the transmission of influenza to the populations at risk of serious complications from influenza. A phased roll-out of the LAIV pilot programme began in 2013/2014. There is limited evidence for vaccine effectiveness (VE) in the populations targeted for influenza vaccination. The aim of this study is to examine the safety and effectiveness of the live attenuated seasonal influenza vaccine programme in children and the inactivated seasonal influenza vaccination programme among different age and at-risk groups of people. Test negative and cohort study designs will be used to estimate VE. A primary care database covering 1.25 million people in Scotland for the period 2000/2001 to 2015/2016 will be linked to the Scottish Immunisation Recall Service (SIRS), Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. Vaccination status (including LAIV uptake) will be determined from the primary care and SIRS database. The primary outcome will be influenza-positive real-time PCR tests carried out in sentinel general practices and other healthcare settings. Secondary outcomes include influenza-like illness and asthma-related general practice consultations, hospitalisations and death. An instrumental variable analysis will be carried out to account for confounding. Self-controlled study designs will be used to estimate the risk of adverse events associated with influenza vaccination. We obtained approval from the National Research Ethics Service Committee, West Midlands-Edgbaston. The study findings will be presented at international conferences and published in peer-reviewed journals. ISRCTN88072400; Pre-results.


Current status of augmentation and combination treatments for major depressive disorder: a literature review and a proposal for a novel approach to improve practice.
Most patients with major depressive disorder (MDD) do not reach symptom remission. These patients with residual symptoms have worse function and worse prognosis than those who remit. Several augmentation and combination treatments are used to either increase the chances of achieving remission or to eliminate/minimize residual depressive symptoms. Evidence for these pharmacological approaches rests primarily on open, uncontrolled studies, and there are clearly not enough controlled studies. Clinicians should carefully weigh these different treatment options to increase their patients' chances of achieving and sustaining remission from depression. This paper will review the pertinent studies and will propose a novel approach to improve practice involving the use of augmentation or combination strategies at the outset of initial treatment to primarily enhance the chances of remission through synergy and/or a broader spectrum of action. This novel approach could potentially enhance retention and/or increase remission rates since the lack of response with antidepressant monotherapy may lead many depressed patients with little or no benefit to drop out of treatment, precluding the subsequent use of augmentation or combination strategies altogether. In addition, the emergence of certain side-effects (e.g., agitation, insomnia) or the persistence of some initial baseline symptoms (e.g., anxiety, insomnia) may lead to premature discontinuation from monotherapy in the absence of concomitant use of augmenting pharmacological options targeting these symptoms.


Excitation and decay of correlated atomic States.
Doubly excited states of atoms and ions in which two electrons are excited from the ground configuration display strong radial and angular electron correlations. They are prototypical examples of quantum-mechanical systems with strong coupling. Two distinguishing characteristics of these states are: (i) their organization into successive families, with only weak coupling between families, and (ii) a hierarchical nature of this coupling, with states from one family decaying primarily to those in the next lower family. A view of the pair of electrons as a single entity, with the electron-electron repulsion between them divided into an adiabatic and a nonadiabatic piece, accounts for many of the dominant features. The stronger, adiabatic part determines the family structure and the weaker, nonadiabatic part the excitation and decay between successive families. Similar considerations extend to three-electron atomic states, which group into five different classes. They are suggestive of composite models for quarks in elementary particle physics, which exhibit analogous groupings into families with a hierarchical arrangement of masses and electroweak decays.


Importance of eye position on spatial localization in blind subjects wearing an Argus II retinal prosthesis.
With a retinal prosthesis connected to a head-mounted camera (camera-connected prosthesis [CC-P]), subjects explore the visual environment through head-scanning movements. As eye and camera misalignment might alter the spatial localization of images generated by the device, we investigated if such misalignment occurs in blind subjects wearing a CC-P and whether it impacts spatial localization, even years after the implantation. We studied three subjects blinded by retinitis pigmentosa, fitted with a CC-P (Argus II) 4 years earlier. Eye/head movements were video recorded as subjects tried to localize a visual target. Pointing coordinates were collected as subjects were requested to orient their gaze toward predetermined directions, and to point their finger to the corresponding perceived spot locations on a touch screen. Finally, subjects were asked to give a history of their everyday behavior while performing visually controlled grasping tasks. Misaligned head and gaze directions occurred in all subjects during free visual search. Pointing coordinates were collected in two subjects and showed that median pointing directions shifted toward gaze direction. Reportedly all subjects were unable to accurately determine their eye position, and they developed adapted strategies to perform visually directed movements. Eye position affected perceptual localization of images generated by the Argus II prosthesis, and consequently visuomotor coordination, even 4 years following implantation. Affected individuals developed strategies for visually guided movements to attenuate the impact of eye and head misalignment. Our observations provide indications for rehabilitation procedures and for the design of upcoming retinal prostheses. (ClinicalTrials.gov number, NCT00407602.).


In situ dynamically monitoring the proteolytic function of the ubiquitin-proteasome system in cultured cardiac myocytes.
The ubiquitin-proteasome system (UPS) is responsible for turnover of most cellular proteins in eukaryotes. Protein degradation by the UPS serves quality control and regulatory functions. Proteasome inhibition showed great promise in effectively treating cancer and restenosis. UPS dysfunction in cardiac hypertrophy and failure has recently been suspected but remains to be investigated. A system capable of monitoring dynamic changes in proteolytic function of the UPS in cardiac myocytes in situ would no doubt benefit significantly efforts to decipher the pathogenic significance of UPS dysfunction in the heart and to evaluate the effect of proteasome inhibition on cardiac myocytes. We successfully established such a system in cultured cardiac myocytes by delivering and expressing a modified green fluorescence protein (GFPu) gene using recombinant adenoviruses. GFPu contains a ubiquitination signal sequence fused to the COOH terminus. Fluorescence microscopy and Western blots revealed that protein abundance of modified green fluorescent protein (GFPu), but not wild-type green fluorescent protein, in cultured cardiac myocytes was incrementally increased when function of the proteasomes was inhibited in various degrees by specific inhibitors. The increase in GFPu protein levels and fluorescence intensity is paralleled by a decrease in the in vitro peptidase activity of the proteasomes. Our results demonstrate that GFPu can be used as a surrogate marker to monitor dynamic changes in proteolytic function of the UPS in cardiac myocytes in situ. Application of this novel system reveals that moderate levels of H2O2, a reactive oxygen species generator, impair proteolytic function of the UPS in cultured cardiac myocytes.


Operative risk in patients with severe obstructive pulmonary disease.
We wanted to determine the risk of postoperative pulmonary complications and mortality in patients with severe chronic obstructive pulmonary disease. We reviewed 107 consecutive operations performed in 89 patients with severe chronic obstructive pulmonary disease (forced expiratory volume in 1 second, less than 50% of predicted). Postoperative pulmonary complications occurred in 31 operations (29%) and were significantly related to the type and duration of surgery. Also, American Society of Anesthesiologists class approached significance as a predictor. Postoperative pulmonary complications occurred at higher rates in coronary artery bypass grafting and major abdominal procedures (60% and 56%) than in other operations involving general or spinal anesthesia (27%) or in procedures performed with the patient under regional or local anesthesia (16%). When the durations of the operations were classified as less than 1 hour, 1 to 2 hours, 2 to 4 hours, and more than 4 hours, the rates of postoperative pulmonary complications were 4%, 23%, 38%, and 73%, respectively. Regarding American Society of Anesthesiologists class, postoperative pulmonary complications occurred in 10% of patients in class II, 28% of those in class III, and 46% of those in class IV. In terms of life-threatening complications, there were six deaths and only two cases of nonfatal ventilatory failure. Notably, mortality clustered primarily in coronary artery bypass graft procedures. Five of 10 patients receiving coronary artery bypass grafts died, compared with one death after 97 non-coronary artery bypass graft operations (50% vs 1%). Although the risk of coronary artery bypass grafting deserves further study, noncardiac surgery carries an acceptable operative risk in patients with severe chronic obstructive pulmonary disease.


AFM combined to ATR-FTIR reveals Candida cell wall changes under caspofungin treatment.
Fungal pathogens from Candida genus are responsible for severe life-threatening infections and the antifungal arsenal is still limited. Caspofungin, an antifungal drug used for human therapy, acts as a blocking agent of the cell wall synthesis by inhibiting the β-1,3-glucan-synthase encoded by FKS genes. Despite its efficiency, the number of genetic mutants that are resistant to caspofungin is increasing. An important challenge to improve antifungal therapy is to understand cellular phenomenon that are associated with drug resistance. Here we used atomic force microscopy (AFM) combined to Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) to decipher the effect of low and high drug concentration on the morphology, mechanics and cell wall composition of two Candida strains, one susceptible and one resistant to caspofungin. Our results confirm that caspofungin induces a dramatic cell wall remodelling via activation of stress responses, even at high drug concentration. Additionally, we highlighted unexpected changes related to drug resistance, suggesting that caspofungin resistance associated with FKS gene mutations comes from a combination of effects: (i) an overall remodelling of yeast cell wall composition; and (ii) cell wall stiffening through chitin synthesis. This work demonstrates that AFM combined to ATR-FTIR is a valuable approach to understand at the molecular scale the biological mechanisms associated with drug resistance.


The early identification of risk factors on the pathway to school dropout in the SIODO study: a sequential mixed-methods study.
School dropout is a persisting problem with major socioeconomic consequences. Although poor health probably contributes to pathways leading to school dropout and health is likely negatively affected by dropout, these issues are relatively absent on the public health agenda. This emphasises the importance of integrative research aimed at identifying children at risk for school dropout at an early stage, discovering how socioeconomic status and gender affect health-related pathways that lead to dropout and developing a prevention tool that can be used in public health services for youth. The SIODO study is a sequential mixed-methods study. A case-control study will be conducted among 18 to 24 year olds in the south of the Netherlands (n = 580). Data are currently being collected from compulsory education departments at municipalities (dropout data), regional public health services (developmental data from birth onwards) and an additional questionnaire has been sent to participants (e.g. personality data). Advanced analyses, including cluster and factor analyses, will be used to identify children at risk at an early stage. Using the quantitative data, we have planned individual interviews with participants and focus groups with important stakeholders such as parents, teachers and public health professionals. A thematic content analysis will be used to analyse the qualitative data. The SIODO study will use a life-course perspective, the ICF-CY model to group the determinants and a mixed-methods design. In this respect, the SIODO study is innovative because it both broadens and deepens the study of health-related determinants of school dropout. It examines how these determinants contribute to socioeconomic and gender differences in health and contributes to the development of a tool that can be used in public health practice to tackle the problem of school dropout at its roots.


Extensive left temporal pole damage does not impact on theory of mind abilities.
The temporal poles (TPs) are among the brain regions that are often considered as the brain network sustaining our ability to understand other people's mental states or "Theory of Mind" (ToM). However, so far the functional role of the left and right TPs in ToM is still debated, and it is even not clear yet whether these regions are necessary for ToM. In this study, we tested whether the left TP is necessary for ToM by assessing the mentalizing abilities of a patient (C.M.) diagnosed with semantic dementia. Converging evidence from detailed MRI and (18)F-fluoro-2-deoxy-d-glucose PET examinations showed a massive atrophy of the left TP with the right TP being relatively unaffected. Furthermore, C.M.'s atrophy encompassed most regions of the left TP usually activated in neuroimaging studies investigating ToM. Given C.M.'s language impairments, we used a battery of entirely nonverbal ToM tasks. Across five tasks encompassing 100 trials, which probed the patient's ability to attribute various mental states (intentions, knowledge, and beliefs), C.M. showed a totally spared performance. This finding suggests that, despite its consistently observed activation in neuroimaging studies involving ToM tasks, the left TP is not necessary for ToM reasoning, at least in nonverbal conditions and as long as its right counterpart is preserved. Implications for understanding the social abilities of patients with semantic dementia are discussed.


Mothers' intentions to support children's physical activity related to attention and implicit agreement with advertisements.
ParticipACTION's Think Again campaign targeted mothers who think their children are sufficiently active, yet whose children do not achieve recommended amounts of physical activity. This research examined the relationship of mothers' intentions to support children's physical activity with explicit believability and implicit agreement with the Think Again campaign message, attention paid to the advertisement, involvement with the issue, concern regarding children's inactivity, and attitudes. Participants were mothers from Edmonton, Canada (N = 102) who viewed one Think Again advertisement then completed a measure of implicit agreement with the campaign message and questionnaires. The mothers who paid attention to the message and were concerned for their own children were more likely to intend to act on campaign messages. The majority of participants implicitly agreed that children's physical inactivity was a problem, but there was less agreement that physical inactivity was a problem for their own children. Participants automatically tended to agree with campaign messages when the focus was on children in general, but there was greater disagreement when asked about participant's own children. Why most mothers were not in agreement with the reality of how much physical activity their children needs remains to be determined.


Does utilization review reduce unnecessary hospital care and contain costs?
Research indicates that approximately one in five hospital admissions is unnecessary or inappropriate, based on accepted clinical criteria. Various cost-containment approaches have been initiated to reduce unnecessary hospital care. Among these approaches, hospital utilization review (UR) has shown promise as a cost-containment strategy. Although third party payers are increasingly relying on UR and similar approaches to contain health care expenditures, little is known about the effects of these efforts. This study analyzes insurance claims data on 223 insured groups for 1984 through 1986 to determine the effects of a UR program instituted by a commercial insurance company. It was found that UR had a significant negative effect on both utilization and expenditures, even after controlling for a large number of factors. Specifically, UR reduced admissions by 13%, inpatient days by 11%, expenditures on routine hospital inpatient services by 7%, expenditures on hospital ancillary services by 9%, and total medical expenditures by 6%. Even though UR reduced the level of utilization and expenditures, it did not appear to influence the rate of change in these areas over time. These findings suggest that hospital UR programs can reduce utilization and expenditures and generate cost savings, thereby helping to improve the efficiency of medical care resources consumption.


Recognition of borderline carbohydrate-lipid metabolism disturbance: an incipient form of type IV hyperlipoproteinemia?
Blood glucose and insulin responses to oral glucose were measured in 33 men: 8 normal, 13 with borderline carbohydrate-lipid metabolism disturbance (BCLMD) (pre-beta-lipoproteinemia with normal cholesterol and triglyceride levels), and 12 with mild Type IV hyperlipoproteinemia. Average age was 30 years, and the percentage of ideal weight was 101%. Borderline patients exhibited hyperinsulinemia following oral glucose, notably at 30 min; they also demonstrated an apparent impairment in homeostatic control of blood glucose level, with a greater-than-normal decline in blood glucose in the 3- to 4-h period (by profile analysis). The Type IV patients, though of normal weight and adiposity, exhibited elevated late incremental insulin area (LIIA) (1-5 h) responses. Combining all data, fasting triglycerides correlated with LIIA (p = 0.0002); LIIA correlated with the percentage of adipose mass (p = 0.003), suggesting that LIIA reflects insulin resistance. Lipoprotein electrophoresis remains useful for detecting pre-beta-lipoproteinemia, which may occur even in persons with normal cholesterol and triglyceride levels. When present, it suggests the possibility of hyperinsulinemia following glucose ingestion, which in turn has been shown to be an independent predictor for the development of coronary heart disease. To gain increased understanding of the natural history of hypertriglyceridemia, persons with BCLMD should be studied separately from those with normal lipid and carbohydrate metabolism and from those with hypertriglyceridemia.


Egyptian women's attitudes and beliefs about female genital cutting and its association with childhood maltreatment.
This study aimed to establish Egyptian women's attitudes and beliefs about female genital cutting (FGC) or mutilation by applying a questionnaire module about violence to a subsample of 5,249 married women from a total of 19,474 women who participated in the 2005 Egypt Demographic Health Survey. Women were interviewed to determine if they had been exposed to marital violence in the year prior to the survey, their attitudes and beliefs about FGC, and if they physically abused their children. The association of beliefs about FGC with maternal physical abuse was examined, adjusting for exposure to marital violence and other socio-demographic variables. Of the women surveyed 16.4% and 3.4% had been exposed to physical and sexual violence, respectively, during the year prior to the survey. Around 76% of the women surveyed intended to continue the FGC practice, and 69.8% had slapped or hit their children during the year prior to the survey. Holding positive beliefs about the practice of FGC or intending to continue it was associated with maternal physical abuse and this has significant implications for health and welfare workers in Egypt and for society in general.


Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life.
Antibiotics have direct effects on the human intestinal microbiota, particularly in infancy. Antibacterial agents promote growth in farm animals by unknown mechanisms, but little is known about their effects on human weight gain. Our aim was to evaluate the impact of antibiotic exposure during infancy on weight and height in healthy Finnish children. The population-based cohort comprised 6114 healthy boys and 5948 healthy girls having primary care weight and height measurements and drug purchase data from birth to 24 months. BMI and height, expressed as z-scores at the median age of 24 months (interquartile range 24 to 26 months), were compared between children exposed and unexposed to antibiotics using analysis of covariance with perinatal factors as covariates. Exposed children were on average heavier than unexposed children (adjusted BMI-for-age z-score difference in boys 0.13 SD [95% confidence interval 0.07 to 0.19, P < .001] and in girls 0.07 SD [0.01 to 0.13, P < .05]). The effect was most pronounced after exposure to macrolides before 6 months of age (boys 0.28 [0.11 to 0.46]; girls 0.23 [0.04 to 0.42]) or >1 exposure (boys 0.20 [0.10 to 0.30]; girls 0.13 [0.03 to 0.22]). Antibiotic exposure before 6 months of age, or repeatedly during infancy, was associated with increased body mass in healthy children. Such effects may play a role in the worldwide childhood obesity epidemic and highlight the importance of judicious use of antibiotics during infancy, favoring narrow-spectrum antibiotics.


Sociodemographic factors influencing island foods consumption in the Pacific Islander Health Study.
Objectives: Pacific Islander Americans are a small, but quickly growing population that experiences alarming disparities in obesity and obesity-related chronic illnesses influenced by dietary patterns. This population also has a unique culinary heritage including traditional foods and more contemporary imports such as tinned meats and refined carbohydrates. This analysis is a novel attempt to understand the sociodemographic factors influencing island foods consumption.Design: A sample of 240 Samoan and Tongan adults in California from the Pacific Islander Health Study was used. Following univariate and bivariate analyses, a series of four multivariable regression models were created to predict past week frequency of island foods consumption after sequential adjustment for demographic, socioeconomic, and cultural covariates.Results: Participants reported consuming island foods an average of 2.93 times in the previous week, with the largest proportion of participants (20.42%) reporting eating island foods 6 or more times. Age and Samoan ethnicity were initially significant, positive predictors of island foods consumption, but their effect was attenuated after addition of cultural covariates. With the third model that adjusted for birthplace, financial insecurity and Tongan birthplace were positive predictors. Both lost significance in the fourth and final model upon addition of cultural affinity, which was positively associated with island foods.Conclusion: Understanding how sociodemographic factors are associated with island foods consumption is a first step in understanding the broad way in which an ethnically specific dietary pattern may be associated with obesity-related chronic illness risk among Pacific Islander Americans.


Twenty nuclear DNA polymorphisms in a Moroccan population: a comparison with seven other human populations.
A south central Moroccan sample was analyzed for 20 nuclear DNA polymorphisms (restriction fragment length polymorphisms). The population was chosen on the basis of available information on its history, making it suitable for comparisons with data from other European populations. The markers analyzed have been studied previously in several human groups from different continents, and data on African and European samples have been compared to evaluate the genetic affinity of the studied sample with other populations, especially with two Spanish groups: Basques and Andalusians. Heterozygosity levels showed intermediate values between the African and European groups and higher than those found so far in an African group for the studied markers. Genetic distances closely matched geographical relationships through neighbor-joining tree and correspondence analysis, the Moroccans being closer to the European groups than the sub-Saharan Africans included in the analysis. Allele distributions revealed specific population associations with large weight of several alleles in the differentiation of some groups. Gene flow from sub-Saharan Africa appears to be relevant in understanding the differentiation of present Moroccan populations.