Industrial wind turbines and adverse health effects.
Some people living in the environs of industrial wind turbines (IWTs) report experiencing adverse health and socioeconomic effects. This review considers the hypothesis that annoyance from audible IWTs is the cause of these adverse health effects. We searched PubMed and Google Scholar for articles published since 2000 that included the terms "wind turbine health," "wind turbine infrasound," "wind turbine annoyance," "noise annoyance" or "low frequency noise" in the title or abstract. Industrial wind turbines produce sound that is perceived to be more annoying than other sources of sound. Reported effects from exposure to IWTs are consistent with well-known stress effects from persistent unwanted sound. If placed too close to residents, IWTs can negatively affect the physical, mental and social well-being of people. There is sufficient evidence to support the conclusion that noise from audible IWTs is a potential cause of health effects. Inaudible low-frequency noise and infrasound from IWTs cannot be ruled out as plausible causes of health effects.


[Protective and damaging effects of periodic cerebral hypoxia: the role of nitric oxide].
Low oxygen delivery to organs and tissues is one of the most life-threatening situations. Periodic hypoxic episodes may have not only damaging, but also protective effects on the organism depending on how long and intensive this factor is. In both cases an important role is played by changes in the synthesis and metabolism of NO. The direction of NO synthesis and, finally, the direction of periodic hypoxia effect is determined by the regimen of hypoxic impact. The effect of NO depends on its concentration. Both NO excess and deficit are very unfavorable to the organism. Sleep apnea syndrome and pulmonary hypertension are typical examples of NO-dependent damaging effects of periodical hypoxia. NO-dependent protective effects of adaptation to periodic hypoxia are underlied by moderate stimulation of NO synthesis, which provides both compensation for NO deficit and the limitation of its hyperproduction. In turn, NO may increase the expression of other protective factors, which makes adaptive protection more reliable and durable. Understanding the mechanisms of adaptation to hypoxia will help develop new approaches to the prevention of hypoxia and ischemic lesions and the improvement of adaptive abilities of the organism.


Endoscopic laser palliation for advanced malignant dysphagia.
Palliative treatment of malignant dysphagia aims to optimise swallowing for the maximum time possible with the minimum of general distress to these seriously ill patients. Thirty four patients considered unsuitable for surgery because of advanced malignancy, other major pathology or in whom previous surgery had been unsuccessful were treated endoscopically with the Nd YAG laser. Significant improvement was achieved in 29 (85%). On a scale of 0-4 (0 = normal swallowing; 4 = dysphagia for all fluids), mean improvement was 1.7, with 25 patients (74%) able to swallow most, or all solids after treatment. With increasing experience, the average number of treatment sessions required for each patient became less; initial time in hospital became comparable to that needed for intubation. Failures were caused by inappropriate patient selection (3), or laser related perforation (2). The mean survival in the whole group was 19 weeks (range 2-44). Eighteen patients needed further treatment for recurrent dysphagia, a mean of six weeks (range 2-15) after initial therapy. Ten of these responded, but eight eventually required insertion of a prosthetic tube. The duration of good palliation was very variable after initial laser therapy.


Puerarin Attenuates N-Methyl-D-aspartic Acid-induced Apoptosis and Retinal Ganglion Cell Damage Through the JNK/p38 MAPK Pathway.
To explore the protective effect of puerarin on N-methyl-D-aspartic acid (NMDA)-induced retinal ganglion cells (RGCs) injury and its underlying mechanism. Primary RGCs were isolated from P3-P7 Sprague-Dawley rats and purified by sequential immunopanning using Thy1.1 antibodies. NMDA was used to mimic the glutamate activation, cell apoptosis, reactive oxygen species (ROS), malondialdehyde levels, SOD and NO production, nNOS and iNOS expression, as well as caspase-3 activity, Bcl-2, and Bax expression in the RGCs were analyzed by ELISA, RT-PCR, and Western blotting. A rat model of retinal injury was used to detect the protective effect of puerarin. Puerarin protected against NMDA-induced RGCs injury in a dose-dependent manner. Compared with the NMDA-treated group, puerarin pretreatment significantly reduced ROS and malondialdehyde levels, promoted SOD and NO production, and downregulated nNOS and iNOS expression in the RGCs. Mechanism analysis showed that pretreatment with puerarin could effectively offset the increase of Bax expression and caspase-3 activity brought by NMDA, and promote Bcl-2 expression in the RGCs. Puerarin pretreatment also effectively inhibited NMDA-induced JNK and p38 phosphorylation in the RGCs, whereas pretreatment with either JNK agonist anisomycin or p38 agonist P79350 could significantly compensate the effects caused by puerarin. Furthermore, puerarin prevented RGCs loss in the retinal injury induced by intravitreal NMDA in a rat model. The present results of this study demonstrated that puerarin protected against NMDA-induced apoptosis and RGCs damage through the JNK/p38 MAPK pathway.


Management of recurrent duodenal ulcer disease.
The purpose of this project was to evaluate the medical and surgical treatment of patients with recurrent peptic ulcer disease and to determine whether the addition of cimetidine has altered the treatment outcome. The authors studied 42 patients with recurrent ulcers after duodenal ulcer surgery. Four patients underwent emergency operation for ulcer-related complications, while 38 patients received medical therapy including cimetidine as initial treatment. Medical therapy achieved good results in 18 of 38 patients (47%). The remaining 20 patients either were treated surgically (14) or are still symptomatic. Four of the 18 patients managed operatively had a second recurrent ulcer (22%). There were no deaths. Thirty-two of the original 42 patients (76%) were helped by the treatment. It was concluded that cimetidine has improved medical therapy compared with historical controls but that operative treatment is indicated in about one-half of patients with recurrent peptic ulcer disease.


Steering the osteoclast through the demineralization-collagenolysis balance.
There is a lot of interest for how and how much osteoclasts resorb bone. However, little is known about the mechanism which controls the orientation and the duration of a resorptive event, thereby determining the specific geometry of a cavitation. Here we show that the relative rate of collagenolysis vs. demineralization plays a critical role in this process. First we observed that when culturing osteoclasts on bone slices, excavations appeared either as round pits containing demineralized collagen, or as elongated trenches without demineralized collagen. This suggests that round pits are generated when collagen degradation is slower than demineralization, and trenches when collagen degradation is as fast as demineralization. Next we treated the osteoclasts with a low dose of a carbonic anhydrase inhibitor to slightly decrease the rate of demineralization, thereby allowing collagen degradation to proceed as fast as demineralization. This resulted in about a two-fold increase of the proportion of trenches, thus supporting our hypothesis. The same result was obtained if facilitating collagen degradation by pre-treating the bone slices with NaOCl. In contrast, when decreasing the rate of collagenolysis vs. demineralization by the addition of a cathepsin K specific inhibitor, the proportion of trenches fell close to 0%, and furthermore the round pits became almost half as deep. These observations lead to a model where the osteoclast resorption route starts perpendicularly to the bone surface, forming a pit, and continues parallel to the bone surface, forming a trench. Importantly, we show that the progress of the osteoclast along this route depends on the balance between the rate of collagenolysis and demineralization. We propose that the osteocytes and bone lining cells surrounding the osteoclast may act on this balance to steer the osteoclast resorptive activity in order to give the excavations a specific shape.


Monoclonal antibody characterization of a unique immune response control locus between H-2S and D.
The primary in vitro antibody response to the type 2 antigen, trinitrophenyl (TNP)-Ficoll, is controlled by two complementing loci in the H-2 region of the mouse major histocompatibility complex (MHC). High responder alleles at both loci are necessary for a high responder phenotype. Previous studies mapped one locus of control to the I-A subregion. In this report we demonstrate by recombinant analysis that the second locus of control is located between the H-2S and D regions. A comparison of responses in the B10.BAR6, B10.BAR10, and B10.BAR11 strains defined a locus controlling the response to TNP-Ficoll in a single haplotype, bounded on the left by the crossover event in the B10.BAR10 and on the right by the crossover event in the B10.BAR6 strain. A monoclonal antibody directed against this right-hand region of control has been produced (48.21.7) that blocks the response to TNP-Ficoll at the level of the antigen-presenting cell. The monoclonal antibody 48-21.7 is specific for the high responder b allele at the right-hand locus and did not inhibit responses to other protein antigens tested. The immune response to TNP-Ficoll was not inhibited by monoclonal antibodies that react with H-2Db or Qa-2 specificities, suggesting that the TNP-Ficoll response is controlled by a unique locus located between H-2S and D. Finally, 48-21.7 recognizes and precipitates a unique product of approximately 40,000 mol wt that is distinct from the H-2D region product recognized by the monoclonal antibody B22/249.


Acute exposure to blue wavelength light during memory consolidation improves verbal memory performance.
Acute exposure to light within the blue wavelengths has been shown to enhance alertness and vigilance, and lead to improved speed on reaction time tasks, possibly due to activation of the noradrenergic system. It remains unclear, however, whether the effects of blue light extend beyond simple alertness processes to also enhance other aspects of cognition, such as memory performance. The aim of this study was to investigate the effects of a thirty minute pulse of blue light versus placebo (amber light) exposure in healthy normally rested individuals in the morning during verbal memory consolidation (i.e., 1.5 hours after memory acquisition) using an abbreviated version of the California Verbal Learning Test (CVLT-II). At delayed recall, individuals who received blue light (n = 12) during the consolidation period showed significantly better long-delay verbal recall than individuals who received amber light exposure (n = 18), while controlling for the effects of general intelligence, depressive symptoms and habitual wake time. These findings extend previous work demonstrating the effect of blue light on brain activation and alertness to further demonstrate its effectiveness at facilitating better memory consolidation and subsequent retention of verbal material. Although preliminary, these findings point to a potential application of blue wavelength light to optimize memory performance in healthy populations. It remains to be determined whether blue light exposure may also enhance performance in clinical populations with memory deficits.


Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells.
We have described here two distinct types of carrier-specific helper T cells which act independently and synergistically to augment the B-cell response to a hapten. They are separable by passage through a nylon wool column. The first type of helper T cell, which we designate as Th1, is nylon nonadherent, and can help the response of hapten-primed B cells only if the haptenic and carrier determinants are present on a single molecule (cognate interaction). The second type of helper T cell, Th2, adheres to the nylon wool column, and can help the B-cell response to a hapten coupled to a heterologous carrier upon stimulation with unconjugated relevant carrier (polyclonal interaction). The addition of a small number of Th2 to the mixture of Th1 and B cells significantly augmented the net response to the hapten carrier conjugate. Both Th1 and Th2 cells belong to the Lyt-1+,2-,3- subclass. Th1 has no detectable Ia antigen, whereas Th2 is killed by certain anti-Ia antisera and complement. The Ia antigen detected on Th2 was found to be controlled by a locus in the I-J subregion. The results clearly established the fact that there are two distinct pathways in the T- and B-cell collaboration, which involves two different subsets of carrier-specific helper T cells.


Dynamic role boundaries in intermediate care services.
This paper examines the impact of intermediate care service delivery on the role boundaries of service providers. Two intermediate care teams were selected as case studies to explore the roles of workers in the context of an admission avoidance and assisted discharge service. Data were collected through semi-structured interviews with 26 intermediate care staff, including physiotherapists, occupational therapists, nurses, a social worker and support workers. The study found that therapists' roles were most closely aligned with each other, whilst nurses perceived their roles as being distinct from therapists, with a more medical emphasis. Therapists and nurses delegate a range of tasks to support workers, although the nature of task delegation differed across the two teams. A number of factors were associated with the role flexibility of staff including the setting, duration and nature of care, access to alternative care providers and the ability of staff to undertake joint visits. Contrary to previous research, the practitioners were not threatened by overlapping roles, and recognised that confidence in their own roles and an understanding of the roles of other workers was necessary to avoid feeling threatened. The study concludes that intermediate care can promote role overlap across a range of workers. Role overlap can enhance clinician confidence in their own area of expertise whilst optimising patient care. Role overlap has the potential to optimise limited staff resources in an interprofessional working environment. Interprofessional working can be enhanced in the workplace through joint visits and shared working practices.


Effects of long-term corset wearing on chronic low back pain.
There are few studies of the therapeutic effects of long-term corset wearing in patients with chronic low back pain. The aim of this study was to evaluate the effects of long-term corset wearing on chronic low back pain and to examine the myoelectrical activities of the paravertebral muscles. Forty subjects with chronic low back pain were enrolled and randomly divided into two groups: a group wearing corsets for 6 months (CW) group and a group not wearing corsets (NW). The treatment effects were measured using the Japanese Orthopaedic Association (JOA) score. Muscle endurance was evaluated during the Biering-Sorensen test (S-test), and the degree of muscle fatigue was evaluated by the change in percent mean power frequency (%MPF) of the paravertebral muscles. Corset treatment for chronic low back pain improved low back pain and increased muscle endurance for a short period of time. Paravertebral muscle fatigue was not increased by long-term corset wearing for chronic low back pain, and weakening of the paravertebral muscles was not observed up to 6 months after the start of corset wearing.


Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study.
The combination of short-acting dihydroartemisinin and long-acting piperaquine (DP) is among the first-line therapies for the treatment of uncomplicated Plasmodium falciparum malaria. Population pharmacokinetic models of piperaquine (PQ) based on data from acute treatment of young children can be used to predict exposure profiles of piperaquine under different DP chemoprevention regimens. The purpose of our study was to make such predictions in young children. Based on a prior population pharmacokinetic model of PQ in young Ugandan children, we simulated capillary plasma concentration-time profiles (including their variability) of candidate chemoprevention regimens for a reference population of 1-2 year olds weighing at least 11 kg. Candidate regimens that were tested included monthly administration of standard therapeutic doses, bimonthly dosing, and weekly dosing (with and without a loading dose). Once daily doses of 320 mg for three days (960 mg total) at the beginning of each month are predicted to achieve an average steady-state trough capillary piperaquine concentration of 35 ng/mL, with 60% achieving a level of 30 ng/mL or higher. In contrast, weekly dosing of 320 mg (i.e., 33% higher amount per month) is predicted to approximately double the average steady-state trough concentration, increase the percent of children predicted to achieve 30 ng/mL or higher (94%), while at the same time lowering peak concentrations. Exposure at steady-state, reached at approximately 3 months of multiple dosing, is expected to be approximately 2-fold higher than exposure following initial dosing, due to accumulation. A loading dose improves early exposure, thereby reducing the risk of breakthrough infections at the initiation of chemoprevention. Once weekly chemoprevention of DP predicts favourable exposures with respect to both trough and peak concentrations. These predictions need to be verified, as well as safety evaluated, in field-based clinical studies of young children. Simulations based on prior knowledge provide a systematic information-driven approach to evaluate candidate DP chemopreventive regimens for future trial designs.


Synthesis, potentiometric, kinetic, and NMR Studies of 1,4,7,10-tetraazacyclododecane-1,7-bis(acetic acid)-4,10-bis(methylenephosphonic acid) (DO2A2P) and its complexes with Ca(II), Cu(II), Zn(II) and lanthanide(III) ions.
A cyclen-based ligand containing trans-acetate and trans-methylenephosphonate pendant groups, H 6DO2A2P, was synthesized and its protonation constants (12.6, 11.43, 5.95, 6.15, 2.88, and 2.77) were determined by pH-potentiometry and (1)H NMR spectroscopy. The first two protonations were shown to occur at the two macrocyclic ring N-CH 2-PO 3 (2-) nitrogens while the third and fourth protonations occur at the two phosphonate groups. In parallel with protonation of the two -PO 3 (2-) groups, the protons from the NH (+)-CH 2-PO 3 (2-) are transferred to the N-CH 2-COO (-) nitrogens. The stability constants of the Ca (2+), Cu (2+), and Zn (2+) (ML, MHL, MH 2L, and M 2L) complexes were determined by direct pH-potentiometry. Lanthanide(III) ions (Ln (3+)) form similar species, but the formation of complexes is slow; so, "out-of-cell" pH-potentiometry (La (3+), Eu (3+), Gd (3+), Y (3+)) and competitive spectrophotometry with Cu(II) ion (Lu (3+)) were used to determine the stability constants. By comparing the log K ML values with those of the corresponding DOTA (H 4DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and DOTP (H 8DOTP = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid) complexes, the order DOTA < DO2A2P < DOTP was found for all the metal ion complexes examined here with the exception of the Ca (2+) complexes, for which the order is reversed. The relaxivity of Gd(DO2A2P) decreases between pH 2 and 7 but remains constant in the pH range of 7 < pH < 12 ( r 1 = 3.6 mM (-1) s (-1)). The linewiths of the (17)O NMR signals of water in the absence and presence of Gd(DO2A2P) (at pH = 3.45 and 8.5) between 274 and 350 K are practically the same, characteristic of a q = 0 complex. Detailed kinetic studies of the Ce (3+) and Gd (3+) complexes with DO2A2P showed that complex formation is slow and involves a high stability diprotonated intermediate Ln(H 2DO2A2P)*. Rearrangement of the diprotonated intermediate into the final complex is an OH (-) assisted process but, unlike formation of Ln(DOTA) complexes, rearrangement of Ln(H 2DO2A2P)* also takes place spontaneously likely as a result of transfer of one of the protons from a ring nitrogen to a phosphonate group. The order of the OH (-) assisted formation rates of complexes is DOTA > DO2A2P > DOTP while the order of the proton assisted dissociation rates of the Gd (3+) complexes is reversed, DOTP > DO2A2P > DOTA. (1)H and (13)C NMR spectra of Eu(DO2A2P) and Lu(DO2A2P) were assigned using two-dimensional correlation spectroscopy (2D COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear chemical shift correlation (HETCOR), and exchange spectroscopy (EXSY) NMR methods. Two sets of (1)H NMR signals were observed for Eu(DO2A2P) characteristic of the presence of two coordination isomers in solution, a twisted square antiprism (TSAP) and a square antiprism (SAP), in the ratio of ~93% and ~7%, respectively. Line shape analysis of the (1)H NMR spectra of Lu(DO2A2P) gave lower activation parameters compared to La(DOTP) for interconversion between coordination isomers. This indicates that the Ln(DO2A2P) complexes are less rigid probably due to the different size and spatial requirements of the carboxylate and phosphonate groups.


Retrospective survey on laparoscopic cholecystectomy in the cirrhotic patient.
Cholelitiasis is a common disease in patients with liver cirrhosis, mainly due to intravascular haemolysis and functional alterations of the gallbladder. In Child A and B cirrhotics laparoscopic cholecystectomy (LC) demonstrated the same advantages and safety as in the non cirrhotic patients. On the contrary, indications for surgery in Child C patients should be carefully evaluated. Nevertheless, the current number of patients with Child C cirrhosis submitted to LC is too low to extrapolate definitive data. Here we report our observations on a retrospective case series of LCs performed for symptomatic biliary disease in patients affected with liver cirrhosis. Both medical records and surgical registers were used to collect pre-operative, intra-operative and post-operative data from 40 cirrhotics out of 921 patients operated by laparoscopic cholecystectomy between November 1996 and November 2006. All patients underwent LC because of symptomatic disease. The average duration of the laparoscopic intervention was 111 minutes (60-220 minutes) distributed as follows according to the severity of liver disease: 66 minutes (48-87) in the Child A group, 108 minutes (91-119) in the Child B group and 138 minutes (110-160) as refers to Child C cirrhotics. Median blood loss was quantified as 80 ml (28-97) in Child A group, 155 ml (130-180) in Child B group and 300 ml (220-500) among Child C cirrhotics. The median length of hospital stay was 6 days (3-9 days) in the Child A group, 9 days (7-13 days) in the Child B group and 21 days (16-27 days) in Child C cirrhotics. Three cases out of 40 (7,5%) died: 2 Child C and 1 Child B. In conclusion, this study confirms that in patients affected with Child A and B cirrhosis LC may be safely performed either in emergency or in election whereas as refers to Child C cases we have observed a slightly higher mortality but a relevant higher impact of non lethal complications.


Communicative gestures in children with delayed onset of oral expressive vocabulary.
Use of communicative gestures in a group of children with delayed onset of expressive oral vocabulary (late talkers) was compared with such use among normal-language-matched controls and age-matched controls. Analyses revealed that late talkers used significantly more communicative gestures and for a greater variety of communicative functions than did language-matched controls. However, a 1-year follow-up revealed that 4 of the late talkers remained delayed (truly delayed late talkers) and 6 caught up (late bloomers). Reanalyses of Year 1 data based on these follow-up outcomes demonstrated that only late bloomers used more communicative gestures than did language-matched controls. Truly delayed late talkers did not differ from language-matched controls either for number of gestures, type of gestures (symbolic vs. nonsymbolic), or number of different functions for which gestures were used. Late bloomers also used more communicative gestures than did age-matched controls, suggesting that they (the late bloomers) were using gestures to compensate for their small oral expressive vocabulary. Results are discussed in the context of early predictors of risk for language impairment and relationships between language and cognition.


Anterior corneal profile with variable asphericity.
We present a corneal profile in which the eccentricity, e(Q=-e(2)), has a nonlinear continuous variation from the center outwards. This nonlinear variation is intended to fit and reproduce our current experimental data in which the anterior corneal surface of the human eye exhibits different values of e at different diameters. According to our clinical data, the variation is similar to an exponential decay. We propose a linear combination of two exponential functions to describe the variation of e. We then calculate the corneal sagittal height by substituting e in the first-order aspherical surface equation to obtain the corneal profile. This corneal profile will be used as a reference to analyze the resultant profiles of the customized corneal ablation in refractive surgery.


Fitness costs in spatially structured environments.
The clustering of individuals that results from limited dispersal is a double-edged sword: although it allows for local interactions to be mostly among related individuals, it also results in increased local competition. Here I show that, because they mitigate local competition, fitness costs such as reduced fecundity or reduced survival are less costly in spatially structured environments than in nonspatial settings. I first present a simple demographic example to illustrate how spatial structure weakens selection against fitness costs. Then, I illustrate the importance of disentangling the evolution of a trait from the evolution of potential associated costs, using an example taken from a recent study investigating the effect of spatial structure on the evolution of host defense. In this example indeed, the differences between spatial and nonspatial selection gradients are due to differences in the fitness costs, thereby undermining interpretations of the results made in terms of the trait only. This illustrates the need to consider fitness costs as proper traits in both theoretical and empirical studies.


Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas.
It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1-5), within and between pituitary tumor types. Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA. Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3>>SSTR1>>>SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2. The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.


SPECT in the localisation of extratemporal and temporal seizure foci.
The yield of ictal, postictal, and interictal SPECT was compared in the localisation of seizure foci in 177 patients with partial epilepsy. In 119 patients with known unilateral temporal lobe epilepsy ictal SPECT (97% correct localisation) was superior to postictal SPECT (71% correct), which was better than interictal studies (48% correct). Similarly, in cases of known or suspected extratemporal epilepsy the yield of ictal SPECT studies was high (92%). By contrast, the yield of postictal studies was much lower (46%) and usually only very early postictal studies were diagnostic. Interictal SPECT was of little value. The accuracy of ictal SPECT in localising temporal lobe seizures is now well established. Extratemporal seizures are often brief and difficult to localise. This report shows that ictal SPECT also has a high diagnostic yield in a wide range of extratemporal epilepsies. The brevity of many extratemporal seizures means that true ictal SPECT examinations can be difficult to achieve, but the high diagnostic yield justifies the special organisational effort needed to obtain such studies.


Temporal and spatial variations in lice numbers on salmon farms in the Hardanger fjord 2004-06.
The long and narrow Hardanger fjord in western Norway has a high density of salmon farms and has had severe salmon lice, Lepeophtheirus salmonis, problems. In the years 2004-06, salmon lice numbers were recorded in selected salmon farms in the fjord as part of a larger research project. Most farm sites participated in a strategic control programme and were deloused between November and January in each year. The aim of the programme was to achieve a mean abundance of <0.3 adult female lice at this time and to minimize the infection pressure on wild smolts in the spring. Dedicated teams carried out detailed counting of lice on farmed fish in April-September each year. Temperature conditions were fairly similar throughout the fjord and amongst years, but wide variations in salinities were observed. The two innermost zones, B and C, had the lowest lice mean abundances, whereas the outermost zones, D and E, consistently had more lice. General linear model analyses showed that differences in adult female lice abundance between the zones were associated with differing levels of salinity and emamectin benzoate treatments strategically administered. Mean fish weight was significantly positively correlated with mean abundance of adult female lice.


Interspecific variation in the relationship between clutch size, laying date and intensity of urbanization in four species of hole-nesting birds.
The increase in size of human populations in urban and agricultural areas has resulted in considerable habitat conversion globally. Such anthropogenic areas have specific environmental characteristics, which influence the physiology, life history, and population dynamics of plants and animals. For example, the date of bud burst is advanced in urban compared to nearby natural areas. In some birds, breeding success is determined by synchrony between timing of breeding and peak food abundance. Pertinently, caterpillars are an important food source for the nestlings of many bird species, and their abundance is influenced by environmental factors such as temperature and date of bud burst. Higher temperatures and advanced date of bud burst in urban areas could advance peak caterpillar abundance and thus affect breeding phenology of birds. In order to test whether laying date advance and clutch sizes decrease with the intensity of urbanization, we analyzed the timing of breeding and clutch size in relation to intensity of urbanization as a measure of human impact in 199 nest box plots across Europe, North Africa, and the Middle East (i.e., the Western Palearctic) for four species of hole-nesters: blue tits (Cyanistes caeruleus), great tits (Parus major), collared flycatchers (Ficedula albicollis), and pied flycatchers (Ficedula hypoleuca). Meanwhile, we estimated the intensity of urbanization as the density of buildings surrounding study plots measured on orthophotographs. For the four study species, the intensity of urbanization was not correlated with laying date. Clutch size in blue and great tits does not seem affected by the intensity of urbanization, while in collared and pied flycatchers it decreased with increasing intensity of urbanization. This is the first large-scale study showing a species-specific major correlation between intensity of urbanization and the ecology of breeding. The underlying mechanisms for the relationships between life history and urbanization remain to be determined. We propose that effects of food abundance or quality, temperature, noise, pollution, or disturbance by humans may on their own or in combination affect laying date and/or clutch size.


Impact of comorbidities on patient outcomes after interferon-free therapy-induced viral eradication in hepatitis C.
Patients with advanced liver fibrosis remain at risk of cirrhosis-related outcomes and those with severe comorbidities may not benefit from hepatitis C (HCV) eradication. We aimed to collect data on all-cause mortality and relevant clinical events within the first two years of direct-acting antiviral therapy, whilst determining the prognostic capability of a comorbidity-based model. This was a prospective non-interventional study, from the beginning of direct-acting antiviral therapy to the event of interest (mortality) or up to two years of follow-up, including 14 Spanish University Hospitals. Patients with HCV infection, irrespective of liver fibrosis stage, who received direct-acting antiviral therapy were used to build an estimation and a validation cohort. Comorbidity was assessed according to Charlson comorbidity and CirCom indexes. A total of 3.4% (65/1,891) of individuals died within the first year, while 5.4% (102/1,891) died during the study. After adjusting for cirrhosis, platelet count, alanine aminotransferase and sex, the following factors were independently associated with one-year mortality: Charlson index (hazard ratio [HR] 1.55; 95% CI 1.29-1.86; p = 0.0001), bilirubin (HR 1.39; 95% CI 1.11-1.75; p = 0.004), age (HR 1.06 95% CI 1.02-1.11; p = 0.005), international normalized ratio (HR 3.49; 95% CI 1.36-8.97; p = 0.010), and albumin (HR 0.18; 95% CI 0.09-0.37; p = 0.0001). HepCom score showed a good calibration and discrimination (C-statistics 0.90), and was superior to the other prognostic scores (model for end-stage liver disease 0.81, Child-Pugh 0.72, CirCom 0.68) regarding one- and two-year mortality. HepCom score identified low- (≤5.7 points: 2%-3%) and high-risk (≥25 points: 56%-59%) mortality groups, both in the estimation and validation cohorts. The distribution of clinical events was similar between groups. The HepCom score, a combination of Charlson comorbidity index, age, and liver function (international normalized ratio, albumin, and bilirubin) enables detection of a group at high risk of one- and two-year mortality, and relevant clinical events, after starting direct-acting antiviral therapy. The prognosis of patients with severe comorbidities may not benefit from HCV viral clearance. An algorithm to decide who will benefit from the treatment is needed to manage the chronic HCV infection better.


Killer-cell immunoglobulin-like receptor and human leukocyte antigen-C genes in common variable immunodeficiency.
We aimed herein to investigate the killer-cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA)-C alleles in patients with common variable immunodeficiency (CVID), and to reveal their differences from those in healthy population. In all, 18 patients who have been diagnosed with CVID and 15 living donors of kidney transplant recipients were enrolled in the study. Polymerase chain reaction-sequence-specific primer (PCR-SSP) typing method was used in molecular genetic analysis. The frequencies of the genes in the study groups were statistically compared with each other using chi-square or Fisher exact tests, whichever were appropriate. Although there was no significant difference between both study groups with respect to distribution of KIR and HLA-C2 group genes, HLA-Cw7 allele frequency in patients with CVID was significantly lower than that in healthy population (P = 0.008). This present study results support that HLA-Cw7 allele, an inhibitor of KIR ligand, may play a role in the pathogenesis of CVID.


KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant.
Copy number variants (CNVs) are major contributors to genetic disorders. We have dissected a region of the 16p11.2 chromosome--which encompasses 29 genes--that confers susceptibility to neurocognitive defects when deleted or duplicated. Overexpression of each human transcript in zebrafish embryos identified KCTD13 as the sole message capable of inducing the microcephaly phenotype associated with the 16p11.2 duplication, whereas suppression of the same locus yielded the macrocephalic phenotype associated with the 16p11.2 deletion, capturing the mirror phenotypes of humans. Analyses of zebrafish and mouse embryos suggest that microcephaly is caused by decreased proliferation of neuronal progenitors with concomitant increase in apoptosis in the developing brain, whereas macrocephaly arises by increased proliferation and no changes in apoptosis. A role for KCTD13 dosage changes is consistent with autism in both a recently reported family with a reduced 16p11.2 deletion and a subject reported here with a complex 16p11.2 rearrangement involving de novo structural alteration of KCTD13. Our data suggest that KCTD13 is a major driver for the neurodevelopmental phenotypes associated with the 16p11.2 CNV, reinforce the idea that one or a small number of transcripts within a CNV can underpin clinical phenotypes, and offer an efficient route to identifying dosage-sensitive loci.


Expert review on poliovirus immunity and transmission.
Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.


[Environmental pollution, climate variability and climate change: a review of health impacts on the Peruvian population].
This article is a review of the pollution of water, air and the effect of climate change on the health of the Peruvian population. A major air pollutant is particulate matter less than 2.5 μ (PM 2.5). In Lima, 2,300 premature deaths annually are attributable to this pollutant. Another problem is household air pollution by using stoves burning biomass fuels, where excessive indoor exposure to PM 2.5 inside the household is responsible for approximately 3,000 annual premature deaths among adults, with another unknown number of deaths among children due to respiratory infections. Water pollution is caused by sewage discharges into rivers, minerals (arsenic) from various sources, and failure of water treatment plants. In Peru, climate change may impact the frequency and severity of El Niño Southern Oscillation (ENSO), which has been associated with an increase in cases of diseases such as cholera, malaria and dengue. Climate change increases the temperature and can extend the areas affected by vector-borne diseases, have impact on the availability of water and contamination of the air. In conclusion, Peru is going through a transition of environmental risk factors, where traditional and modern risks coexist and infectious and chronic problems remain, some of which are associated with problems of pollution of water and air.


Nile red dye in aqueous surfactant and micellar solution.
The solubilization behavior of nile red dye in aqueous surfactant and micellar solutions was studied by optical spectroscopic techniques, dynamic light scattering, and atomic force microscopy. Nile red exhibits considerable absorption in the submicellar concentration region. When dispersed in aqueous surfactant and/or micellar solution, nile red molecules tend to form nonemissive dimers and/or H-type aggregates through π-π stacking interactions. This phenomenon may limit the use of nile red in solubilization studies. In the presence of ionic SDS and CTAB micelles, the solubilization of nile red appears to take place primarily at the charged micellar surface within the interfacial region. Similarly, spectra in micellar solution of nonionic Triton X-100 revealed that nile red dye penetrates the hydrophilic, interfacial poly(oxyethylene) region of the micelles but cannot reach the hydrophobic, innermost core. Our results therefore suggest that nile red dye must be chosen carefully when probing (micellar) hydrophobic environments and (micro)domains.


Neonicotinoids act like endocrine disrupting chemicals in newly-emerged bees and winter bees.
Accumulating evidence suggests that neonicotinoids may have long-term adverse effects on bee health, yet our understanding of how this could occur is incomplete. Pesticides can act as endocrine disrupting chemicals (EDCs) in animals providing characteristic multiphasic dose-response curves and non-lethal endpoints in toxicity studies. However, it is not known if neonicotinoids act as EDCs in bees. To address this issue, we performed oral acute and chronic toxicity studies including concentrations recorded in nectar and pollen, applying acetamiprid, clothianidin, imidacloprid, and thiamethoxam to bumble bees, honey bees and leafcutter bees, the three most common bee species managed for pollination. In acute toxicity studies, late-onset symptoms, such as ataxia, were recorded as non-lethal endpoints for all three bee species. Clothianidin and thiamethoxam produced biphasic dose-response curves for all three bee species. Clothianidin and thiamethoxam were extremely toxic to winter worker honey bees prior to brood production in spring, making this the most sensitive bee stage identified to date. Chronic exposure to field-realistic levels of neonicotinoids reduced bee survival and caused significant late-onset symptoms for all three bee species. Given these findings, neonicotinoid risk should be reevaluated to address the EDC-like behavior and the sensitivity of winter worker honey bees.


Architectural design and physical activity: an observational study of staircase and elevator use in different buildings.
The indoor built environment has the potential to influence levels of physical activity. However, the extent to which architectural design in commercial buildings can influence the percentage of people choosing to use the stairs versus elevators is unknown. The purpose of this study was to determine if buildings with centrally located, accessible, and aesthetically pleasing staircases result in a greater percentage of people taking the stairs. Direct observations of stair and elevator use were conducted in 3 buildings on a university campus. One of the buildings had a bank of 4 centrally located elevators and a fire escape stairwell behind a steel door. The other 2 buildings had centrally located staircases and out-of-the-way elevators. The percentage of people who ascended the stairs was 8.1% in the elevator-centric building, compared with 72.8% and 81.1% in the 2 stair-centric buildings (P < .001). In addition, the percentage of people who descended the stairs was 10.8% in the first building, compared with 89.5% and 93.7% in the stair-centric buildings (P < .001). The results of the current study suggest that if buildings are constructed with centrally located, accessible, and aesthetically pleasing staircases, a greater percentage of people will choose to take the stairs.


Huckebein repressor activity in Drosophila terminal patterning is mediated by Groucho.
The Groucho corepressor mediates negative transcriptional regulation in association with various DNA-binding proteins in diverse developmental contexts. We have previously implicated Groucho in Drosophila embryonic terminal patterning, showing that it is required to confine tailless and huckebein terminal gap gene expression to the pole regions of the embryo. Here we reveal an additional requirement for Groucho in this developmental process by establishing that Groucho mediates repressor activity of the Huckebein protein. Putative Huckebein target genes are derepressed in embryos lacking maternal groucho activity and biochemical experiments demonstrate that Huckebein physically interacts with Groucho. Using an in vivo repression assay, we identify a functional repressor domain in Huckebein that contains an FRPW tetrapeptide, similar to the WRPW Groucho-recruitment domain found in Hairy-related repressor proteins. Mutations in Huckebein's FRPW motif abolish Groucho binding and in vivo repression activity, indicating that binding of Groucho through the FRPW motif is required for the repressor function of Huckebein. Taken together with our earlier results, these findings show that Groucho-repression regulates sequential aspects of terminal patterning in Drosophila.


Luminescent europium and terbium complexes of dipyridoquinoxaline and dipyridophenazine ligands as photosensitizing antennae: structures and biological perspectives.
The europium(III) and terbium(III) complexes, namely [Eu(dpq)(DMF)2(NO3)3] (1), [Eu(dppz)2(NO3)3] (2), [Tb(dpq)(DMF)2Cl3] (3), and [Tb(dppz)(DMF)2Cl3] (4), where dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 1 and 3), dipyrido[3,2-a:2',3'-c]phenazine (dppz in 2 and 4) and N,N'-dimethylformamide (DMF) have been isolated, characterized from their physicochemical data, luminescence studies and their interaction with DNA, serum albumin protein and photo-induced DNA cleavage activity are studied. The X-ray crystal structures of complexes 1-4 show discrete mononuclear Ln(3+)-based structures. The Eu(3+) in [Eu(dpq)(DMF)2(NO3)3] (1) and [Eu(dppz)2(NO3)3] (2) as [Eu(dppz)2(NO3)3]·dppz (2a) adopts a ten-coordinated bicapped dodecahedron structure with a bidentate N,N-donor dpq ligand, two DMF and three NO3(-) anions in 1 and two bidentate N,N-donor dppz ligands and three NO3(-) anions in 2. Complexes 3 and 4 show a seven-coordinated mono-capped octahedron structure where Tb(3+) contains bidentate dpq/dppz ligands, two DMF and three Cl(-) anions. The complexes are highly luminescent in nature indicating efficient photo-excited energy transfer from the dpq/dppz antenna to Ln(3+) to generate long-lived emissive excited states for characteristic f → f transitions. The time-resolved luminescence spectra of complexes 1-4 show typical narrow emission bands attributed to the (5)D0 → (7)F(J) and (5)D4 → (7)F(J) f-f transitions of Eu(3+) and Tb(3+) ions respectively. The number of inner-sphere water molecules (q) was determined from luminescence lifetime measurements in H2O and D2O confirming ligand-exchange reactions with water in solution. The complexes display significant binding propensity to the CT-DNA giving binding constant values in the range of 1.0 × 10(4)-6.1 × 10(4) M(-1) in the order 2, 4 (dppz) > 1, 3 (dpq). DNA binding data suggest DNA groove binding with the partial intercalation nature of the complexes. All the complexes also show binding propensity (K(BSA) ∼ 10(5) M(-1)) to the bovine serum albumin (BSA) protein. The intensity of the time-gated luminescence spectral bands enhances significantly with the increasing DNA concentration in aqueous buffer medium due to displacement of bound water upon interaction with DNA, thus reducing non-radiative quenching through the O-H oscillator. Complexes 1-4 efficiently cleave supercoiled (SC) ds-DNA to its nicked circular (NC) form on exposure to UV-A light of 365 nm via formation of singlet oxygen ((1)O2) and hydroxyl radicals (HO˙) as the reactive oxygen species at micromolar concentrations under physiological conditions.


Effects of spontaneous bilayer curvature on influenza virus-mediated fusion pores.
Cells expressing the hemagglutinin protein of influenza virus were fused to planar bilayer membranes containing the fluorescent lipid probes octadecylrhodamine (R18) or indocarbocyanine (DiI) to investigate whether spontaneous curvature of each monolayer of a target membrane affects the growth of fusion pores. R18 and DiI lowered the transition temperatures for formation of an inverted hexagonal phase, indicating that these probes facilitate the formation of negative curvature structures. The probes are known to translocate from one monolayer of a bilayer membrane to the other in a voltage-dependent manner. The spontaneous curvature of the cis monolayer (facing the cells) or the trans monolayer could therefore be made more negative through control of the polarity of voltage across the planar membrane. Electrical admittance measurements showed that the open times of flickering fusion pores were shorter when probes were in trans monolayers and longer when in cis monolayers compared with times when probe was symmetrically distributed. Open times were the same for probe symmetrically distributed as when probes were not present. Thus, open times were a function of the asymmetry of the spontaneous curvature between the trans and cis monolayers. Enriching the cis monolayer with a negative curvature probe reduced the probability that a small pore would fully enlarge, whereas enriching the trans monolayer promoted enlargement. Lysophosphatidylcholine has positive spontaneous curvature and does not translocate. When lysophosphatidylcholine was placed in trans leaflets of planar membranes, closing of fusion pores was rare. The effects of the negative and positive spontaneous curvature probes do not support the hypothesis that a flickering pore closes from an open state within a hemifusion diaphragm (essentially a "flat" structure). Rather, such effects support the hypothesis that the membrane surrounding the open pore forms a three-dimensional hourglass shape from which the pore flickers shut.


Improving resource mobilisation for global health R&D: a role for coordination platforms?
Achieving many of the health targets in the Sustainable Development Goals will not be possible without increased financing for global health research and development (R&D). Yet financing for neglected disease product development fell from 2009-2015, with the exception of a one-time injection of Ebola funding. An important cause of the global health R&D funding gap is lack of coordination across R&D initiatives. In particular, existing initiatives lack robust priority-setting processes and transparency about investment decisions. Low-income countries (LICs) and middle-income countries (MICs) are also often excluded from global investment initiatives and priority-setting discussions, leading to limited investment by these countries. An overarching global health R&D coordination platform is one promising response to these challenges. This analysis examines the essential functions such a platform must play, how it should be structured to maximise effectiveness and investment strategies for diversifying potential investors, with an emphasis on building LIC and MIC engagement. Our analysis suggests that a coordination platform should have four key functions: building consensus on R&D priorities; facilitating information sharing about past and future investments; building in accountability mechanisms to track R&D spending against investment targets and curating a portfolio of prioritised projects alongside mechanisms to link funders to these projects. Several design features are likely to increase the platform's success: public ownership and management; separation of coordination and financing functions; inclusion of multiple diseases; coordination across global and national efforts; development of an international R&D 'roadmap' and a strategy for the financial sustainability of the platform's secretariat.


Quantization of Dextromethorphan and Levocetirizine in Combined Dosage form Using a Novel Validated RP-HPLC Method.
The present study reveals a simple isocratic RP-HPLC method for the simultaneous determination of dextromethorphan hydrobromide and levocetirizine dihydrochloride in a cough syrup. The separation of these compounds was achieved within 10 min on a Phenomenex (USA) C(18) analytical column, 250×4.0 mm i.d., using an isocratic mobile phase consisting of potassium dihydrogen phosphate buffer (pH 2.5) - acetonitrile- tetrahydrofuran (70:25:5, v/v/v). The analysis was performed at a flow rate of 1.2 ml/min and at a detection wavelength of 232 nm. Percentage recovery and RSD were 100.36% and 0.05% for levocetirizine dihydrochloride, 100.35% and 0.27% for dextromethorphan hydrobromide respectively. Quantification of the components in syrup formulation was calculated against the peak areas of freshly prepared standard solutions. The method was validated as per ICH guidelines.


Recent advances in miniaturization-the role of microchip electrophoresis in clinical analysis.
This review is a follow-up from the last review published in 2012 that covers the same topic [22]. Its aim is to cover new innovations and developments since then, involving the role of microchip capillary electrophoresis (MCE) in clinical analysis. MCE has shown great promise in separation science, as it's a state-of-the-art analytical separation technique that offers speed, portability, reduced sample, and reagent requirements, repeatability, can be used online or offline, and can be coupled with many kinds of analytical detectors. It is particularly important in clinical analysis, as it offers online continuous monitoring, can handle small volumes of highly complex biological samples due to its powerful discriminating ability, and it facilitates point-of-care testing. Also microchip separation platforms have been used for sample clean-up, filtration, derivatization, separation and detection, acting as multifunctional platforms ideal for minute sample volumes. In recent times the clinical world has witnessed a need for rapid turnaround times on analysis of very complex samples, and so there has been a shift toward point-of-care testing and other miniaturized analytical techniques as a favorable solution. Research developments in this area have been catalyzed by rapid strides in knowledge in the areas of proteomics, metabolomics, and molecular biology in the quest to understand the physiology of cells, proteins, genes, molecular interactions, and the pathophysiology of disease. Herein, we present selected examples detailing the use of MCE in some of the latest and most exciting clinical applications.


Life Expectancy and Mortality Rates in the United States, 1959-2017.
US life expectancy has not kept pace with that of other wealthy countries and is now decreasing. To examine vital statistics and review the history of changes in US life expectancy and increasing mortality rates; and to identify potential contributing factors, drawing insights from current literature and an analysis of state-level trends. Life expectancy data for 1959-2016 and cause-specific mortality rates for 1999-2017 were obtained from the US Mortality Database and CDC WONDER, respectively. The analysis focused on midlife deaths (ages 25-64 years), stratified by sex, race/ethnicity, socioeconomic status, and geography (including the 50 states). Published research from January 1990 through August 2019 that examined relevant mortality trends and potential contributory factors was examined. Between 1959 and 2016, US life expectancy increased from 69.9 years to 78.9 years but declined for 3 consecutive years after 2014. The recent decrease in US life expectancy culminated a period of increasing cause-specific mortality among adults aged 25 to 64 years that began in the 1990s, ultimately producing an increase in all-cause mortality that began in 2010. During 2010-2017, midlife all-cause mortality rates increased from 328.5 deaths/100 000 to 348.2 deaths/100 000. By 2014, midlife mortality was increasing across all racial groups, caused by drug overdoses, alcohol abuse, suicides, and a diverse list of organ system diseases. The largest relative increases in midlife mortality rates occurred in New England (New Hampshire, 23.3%; Maine, 20.7%; Vermont, 19.9%) and the Ohio Valley (West Virginia, 23.0%; Ohio, 21.6%; Indiana, 14.8%; Kentucky, 14.7%). The increase in midlife mortality during 2010-2017 was associated with an estimated 33 307 excess US deaths, 32.8% of which occurred in 4 Ohio Valley states. US life expectancy increased for most of the past 60 years, but the rate of increase slowed over time and life expectancy decreased after 2014. A major contributor has been an increase in mortality from specific causes (eg, drug overdoses, suicides, organ system diseases) among young and middle-aged adults of all racial groups, with an onset as early as the 1990s and with the largest relative increases occurring in the Ohio Valley and New England. The implications for public health and the economy are substantial, making it vital to understand the underlying causes.


Prediction of metallic nanotube reactivity for H2O activation.
The reactivity of metallic nanotubes toward the catalysis of water dissociation, a key step in the water gas shift reaction (WGSR), was analyzed through density functional theory (DFT) calculations. Water dissociation was studied on surfaces of nanotubes based on copper, gold and platinum, and also on platinum doped copper and gold nanotubes. Gold and copper nanotubes present activities that are similar to those of their corresponding extended surfaces but, in the case of the Pt(5,3) nanotube, a significant improvement in the activity is found when compared with the extended surfaces. In fact, the calculations predict the water dissociation to be spontaneous on Pt(5,3) with a low activation energy barrier. The platinum doping of gold and copper nanotubes leads to contrasting effects, i.e., with a slight increase of activity found on gold and a slight decrease of activity in the case of copper. The consideration of a Brönsted-Evans-Polanyi (BEP) relationship to estimate the activation energy barriers for the O-H bond break leads to a satisfactory agreement between estimated and explicitly calculated values which suggests the validity of the BEP relationship for qualitative predictions of the activities of metal nanotubes towards the water dissociation reaction.


Localizing transcriptional regulatory elements at the mouse Dlk1 locus.
Much effort has focused recently on determining the mechanisms that control the allele-specific expression of genes subject to genomic imprinting, yet imprinting regulation is only one aspect of configuring appropriate expression of these genes. Imprinting control mechanisms must interact with those regulating the tissue-specific expression pattern of each imprinted gene in a cluster. Proper expression of the imprinted Delta-like 1 (Dlk1)-Maternally expressed gene 3 (Meg3) gene pair is required for normal fetal development in mammals, yet the mechanisms that control tissue-specific expression of these genes are unknown. We have used a combination of in vivo and in vitro expression assays to localize cis-regulatory elements that may regulate Dlk1 expression in the mouse embryo. A bacterial artificial chromosome transgene encompassing the Dlk1 gene and 77 kb of flanking sequence conferred expression in most endogenous Dlk1-expressing tissues. In combination with previous transgenic data, these experiments localize the majority of Dlk1 cis-regulatory elements to a 41 kb region upstream of the gene. Cross-species sequence conservation was used to further define potential regulatory elements, several of which functioned as enhancers in a luciferase expression assay. Two of these elements were able to drive expression of a lacZ reporter transgene in Dlk1-expressing tissues in the mouse embryo. The sequence proximal to Dlk1 therefore contains at least two discrete regions that may regulate tissue-specificity of Dlk1 expression.


Rapid closure technique in decompressive craniectomy.
The object of this study was to describe the rapid closure technique in decompressive craniectomy without duraplasty and its use in a large cohort of consecutive patients. Between 1999 and 2008, supratentorial rapid closure decompressive craniectomy (RCDC) was performed 341 times in 318 patients at the authors' institution. Cases were stratified as 1) traumatic brain injury, 2) subarachnoid hemorrhage, 3) intracerebral hemorrhage, 4) cerebral infarction, and 5) other. A large bone flap was removed and the dura mater was opened in a stellate fashion. Duraplasty was not performed-that is, the dura was not sutured, and a dural substitute was neither sutured in nor layed on. The dura and exposed brain tissue were covered with hemostyptic material (Surgicel). Surgical time and complications of this procedure including follow-up (> 6 months) were recorded. After 3-6 months cranioplasty was performed, and, again, surgical time and any complications were recorded. Rapid closure decompressive craniectomy was feasible in all cases. Complications included superficial wound healing disturbance (3.5% of procedures), abscess (2.6%) and CSF fistula (0.6%); the mean surgical time (± SD) was 69 ± 20 minutes. Cranioplasty was performed in 196 cases; the mean interval (± SD) from craniectomy to cranioplasty was 118 ± 40 days. Complications of cranioplasty included epidural hematoma (4.1%), abscess (2.6%), wound healing disturbance (6.1%), and CSF fistula (1%). Compared with the results reported in the literature for decompressive craniectomy with duraplasty followed by cranioplasty, there were no significant differences in the frequency of complications. However, surgical time for RCDC was significantly shorter (69 ± 20 vs 129 ± 43 minutes, p < 0.0001). The present analysis of the largest series reported to date reveals that the rapid closure technique is feasible and safe in decompressive craniectomy. The surgical time is significantly shorter without increased complication rates or additional complications. Cranioplasty after a RCDC procedure was also feasible, fast, safe and not impaired by the RCDC technique.


Sonographically guided popliteus tendon sheath injection: techniques and accuracy.
The purpose of this investigation was to describe two sonographically guided popliteus tendon sheath injection techniques and determine their accuracy in a cadaveric model. A single experienced operator completed 24 sonographically guided popliteus tendon sheath injections, 12 using a longitudinal approach and 12 using a transverse approach relative to the tendon. The injection order was randomized, and all injections were completed with diluted colored latex. Coinvestigators blinded to the injection technique dissected each specimen and graded the colored latex location as accurate (in the sheath), accurate with overflow (within the sheath but also in other regions), or inaccurate (no latex in the sheath). All 12 sonographically guided popliteus sheath injections using the longitudinal approach placed latex into the sheath. Eight of these injections (67%) also resulted in overflow into the knee joint. Ten of 12 transverse approach injections placed latex into the sheath (83%), with 7 of these (70%) also producing overflow into the knee joint. Two of 12 transverse injections (17%) placed latex only into the knee joint and were therefore inaccurate. Sonographic guidance can be used to inject the popliteus tendon sheath with a high degree of accuracy. Although the longitudinal approach is potentially more accurate, both approaches may result in injectate overflow into the knee joint, likely through the popliteus hiatus.


Meta-analysis of controlled studies on immunotherapy in severe scorpion envenomation.
Despite conflicting evidence, specific serotherapy is recommended for scorpion envenomation. A meta-analysis of prospective or observational controlled studies, comparing intravenous scorpion antivenin (SAV) with control, was performed. Binary outcomes are reported as risk difference for clinical improvement and mortality rates. Analysis was performed both for the whole number of included studies and for two subgroups (set up according to the geographic origin of scorpions). Nine studies (four randomised controlled trials (RCTs), five observational) enrolling 687 patients were identified. Six dealt with Old World scorpions and three originated from Arizona. Overall, the rate of clinical improvement was similar in SAV treated and untreated patients (risk difference=0.22, 95% CI -0.35 to 0.79; p=0.45 for effect). Subgroup analysis showed favourable effects of SAV in the Arizona scorpion envenomation (risk difference=0.53; 95% CI 0.16 to 0.91; p<0.001), and non-significant unfavourable effects in Old World scorpion envenomation (risk difference=-0.05; 95% CI -0.28 to 0.18; p=0.65; p=0.003 for z-value, indicating a true heterogeneity of treatment effects). In Old World scorpion envenomation, there was no statistical difference in the risk of death in SAV treated and untreated scorpion envenomated patients (risk difference=0.007, 95% CI -0.02 to 0.03; p=0.6 for effect). Overall, administration of scorpion antivenin was associated with a reduction by 13 h in the mean time of symptom resolution (95% CI -17 to -9; p<0.0001). Serious adverse events were reported at a rate of 1-2% while minor adverse events occurred in up to 40% of patients. SAV should not be administered in Old World scorpion envenomation until its efficacy is established by an appropriately designed RCT. In the Arizona scorpion sting, SAV hastens the recovery process.


Predictors of antibiotic prescribing for nonspecific upper respiratory infections, acute bronchitis, and acute sinusitis. An UPRNet study. Upper Peninsula Research Network.
Antibiotics are often prescribed for viral respiratory infections. The goal of our study was to determine the factors associated with antibiotic prescribing for acute respiratory infections in primary care. We performed an observational study in 15 primary care practices in Michigan using patient and physician surveys distributed during visits for acute respiratory infections. We included patients 4 years or older presenting with symptoms of an acute respiratory infection (n=482). The main outcome measures were prescriptions of antibiotics, signs and symptoms associated with antibiotic prescribing, and clinician-reported reasons for prescribing an antibiotic. We found that patients who were older than 18 years, sick for more than 14 days, and seen in urgent care clinics were more likely to receive antibiotics. Patients expected antibiotics if they perceived that the drug had helped with similar symptoms in the past. In an adjusted model, the variables significantly associated with antibiotic prescribing were physical findings of sinus tenderness (odds ratio [OR]=20.0; 95% confidence interval [CI], 8.3-43.2), rales/rhonchi (OR=19.9; 95% CI, 9.2-43.2), discolored nasal discharge (OR=11.7; 95% CI, 4.3-31.7), and postnasal drainage (OR=3.1; 95% CI, 1.6-6.0). The presence of clear nasal discharge on examination was negatively associated (OR=0.3; 95% CI, 0.2-0.5). Several physical signs play an important role in clinicians' decisions to prescribe antibiotics for respiratory infections. This information will be useful in designing interventions to decrease inappropriate antibiotic prescribing for upper respiratory infections.


A biorobotic model of the sunfish pectoral fin for investigations of fin sensorimotor control.
A comprehensive understanding of the control of flexible fins is fundamental to engineering underwater vehicles that perform like fish, since it is the fins that produce forces which control the fish's motion. However, little is known about the fin's sensory system or about how fish use sensory information to modulate the fin and to control propulsive forces. As part of a research program that involves neuromechanical and behavioral studies of the sunfish pectoral fin, a biorobotic model of the pectoral fin and of the fin's sensorimotor system was developed and used to investigate relationships between sensory information, fin ray motions and propulsive forces. This robotic fin is able to generate the motions and forces of the biological fin during steady swimming and turn maneuvers, and is instrumented with a relatively small set of sensors that represent the biological lateral line and receptors hypothesized to exist intrinsic to the pectoral fin. Results support the idea that fin ray curvature, and the pressure in the flow along the wall that represents the fish body, capture time-varying characteristics of the magnitude and direction of the force created throughout a fin beat. However, none of the sensor modalities alone are sufficient to predict the propulsive force. Knowledge of the time-varying force vector with sufficient detail for the closed-loop control of fin ray motion will result from the integration of characteristics of many sensor modalities.


Quality evaluation of methyl binding domain based kits for enrichment DNA-methylation sequencing.
DNA-methylation is an important epigenetic feature in health and disease. Methylated sequence capturing by Methyl Binding Domain (MBD) based enrichment followed by second-generation sequencing provides the best combination of sensitivity and cost-efficiency for genome-wide DNA-methylation profiling. However, existing implementations are numerous, and quality control and optimization require expensive external validation. Therefore, this study has two aims: 1) to identify a best performing kit for MBD-based enrichment using independent validation data, and 2) to evaluate whether quality evaluation can also be performed solely based on the characteristics of the generated sequences. Five commercially available kits for MBD enrichment were combined with Illumina GAIIx sequencing for three cell lines (HCT15, DU145, PC3). Reduced representation bisulfite sequencing data (all three cell lines) and publicly available Illumina Infinium BeadChip data (DU145 and PC3) were used for benchmarking. Consistent large-scale differences in yield, sensitivity and specificity between the different kits could be identified, with Diagenode's MethylCap kit as overall best performing kit under the tested conditions. This kit could also be identified with the Fragment CpG-plot, which summarizes the CpG content of the captured fragments, implying that the latter can be used as a tool to monitor data quality. In conclusion, there are major quality differences between kits for MBD-based capturing of methylated DNA, with the MethylCap kit performing best under the used settings. The Fragment CpG-plot is able to monitor data quality based on inherent sequence data characteristics, and is therefore a cost-efficient tool for experimental optimization, but also to monitor quality throughout routine applications.


Jitter-free multi-layered nanoparticles optical storage disk with buffer ring.
A multi-layered nanoparticles optical disk has been developed for a jitter-free high-density data storage system. The disk has nano structures composed of 300-nm-diameter photosensitive particles and 30-nm-width non-photosensitive buffer rings around them. With the buffer rings into the nanoparticles disk, a conventional confocal microscope equipped with a low numerical aperture (NA) objective picked up a particle's shape signal to generate a synchronous signal on its own. In the three-dimensional structured disk proposed, no electronically-produced reference signal is necessary for clock data recover (CDR); no jitter occurs in data decoding.


Antiseptic efficacy and tolerance of tissue-tolerable plasma compared with two wound antiseptics on artificially bacterially contaminated eyes from commercially slaughtered pigs.
To compare the tissue tolerance and efficacy of two wound antiseptics with tissue-tolerable plasma (TTP) on enucleated contaminated eyes from slaughtered pigs in order to draw consequences for the use of TTP on wounds. The corneas of extracted eyes were contaminated with Staphylococcus aureus or Pseudomonas aeruginosa. One and 10 min after application of 10% povidone (PVP)-iodine and 0.04% polyhexanide, respectively, the eyes were rinsed with inactivating solution. To test TTP, the plasma pen meandered over the eyes at a speed of 30 mm/s and a distance of 5 mm; the eyes were then rinsed with balanced salt solution. The reduction factor was calculated by the difference between the logarithm of colony-forming units in the rinse before and after antisepsis or TTP application. The efficacy of TTP (reduction factor 2.4-2.9) was significantly higher (p < 0.001) than that of PVP-iodine and polyhexanide (reduction factor 1.7-2.1). TTP is more effective than the tested wound antiseptics. The lack of histological damage to the eyes of slaughtered pigs would seem to make its use as a wound antiseptic a viable alternative. In contrast to antiseptics, it supplies additional energy in the form of heat, electric fields and radicals by TTP.


Antifreezing Gold Colloids.
Gold (Au) colloids are becoming ubiquitous across biomedical engineering, solar energy conversion, and nano-optics. Such universality has originated from the exotic plasmonic effect of Au colloids (i.e., localized surface plasmon resonance (LSPRs)) in conjunction with the versatile access to their synthetic routes. Herein, we introduce a previously undiscovered usage of Au colloids for advancing cryoprotectants with significant ice recrystallization inhibition (IRI). Oligopeptides inspired by the antifreeze protein (AFP) and antifreeze glycoprotein (AFGP) are attached onto the surface of well-defined Au colloids with the same sizes but different shapes. These AF(G)P-inspired Au colloids can directly adsorb onto a growing ice crystal via the synergistic interplay between hydrogen bonding and hydrophobic groups, in stark contrast to their bare Au counterparts. Dark-field optical microscopy analyses, benefiting from LSPR, allow us to individually trace the in situ movement of the antifreezing Au colloids during ice growth/recrystallization and clearly evidence their direct adsorption onto the growing ice crystal, which is consistent with theoretical predictions. With the assistance of molecular dynamics (MD) simulations, we evidently attribute the IRI of AF(G)P-inspired Au colloids to the Kelvin effect. We also exploit the IRI dependence on the Au colloidal shapes; indeed, the facet contacts between ice and Au colloids can be better than the point-like counterparts in terms of IRI. The design principles and predictive theory outlined in this work will be of broad interest not only for the fundamental exploration of the inhibition of ice growth but also for enriching the application of Au colloids.


Delineating the Rules for Structural Adaptation of Membrane-Associated Proteins to Evolutionary Changes in Membrane Lipidome.
Membrane function is fundamental to life. Each species explores membrane lipid diversity within a genetically predefined range of possibilities. How membrane lipid composition in turn defines the functional space available for evolution of membrane-centered processes remains largely unknown. We address this fundamental question using related fission yeasts Schizosaccharomyces pombe and Schizosaccharomyces japonicus. We show that, unlike S. pombe that generates membranes where both glycerophospholipid acyl tails are predominantly 16-18 carbons long, S. japonicus synthesizes unusual "asymmetrical" glycerophospholipids where the tails differ in length by 6-8 carbons. This results in stiffer bilayers with distinct lipid packing properties. Retroengineered S. pombe synthesizing the S.-japonicus-type phospholipids exhibits unfolded protein response and downregulates secretion. Importantly, our protein sequence comparisons and domain swap experiments support the hypothesis that transmembrane helices co-evolve with membranes, suggesting that, on the evolutionary scale, changes in membrane lipid composition may necessitate extensive adaptation of the membrane-associated proteome.


Factor structure of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) in a large sample of patients with schizophrenia or related disorders and comorbid obsessive-compulsive symptoms.
In the past decade there has been an increasing interest in the levels of obsessive-compulsive symptoms (OCS) found in patients with schizophrenia or related disorders. The widely acknowledged gold standard measure of the severity of OCS is the content-free version of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (Goodman et al., 1989a,b). However, factor analytic research in patients with obsessive-compulsive disorder (OCD) provided varied results. So far no study has been conducted on the factor structure of the Y-BOCS in patients with schizophrenia. The present study addresses this issue. We administered the Y-BOCS in a sample of 217 patients with schizophrenia or related disorders and comorbid OCS who participated in a multicentre cohort study. We used principal component analysis (PCA) to explore the underlying factor structure. A two-factor solution consistent with the originally proposed scoring structure of the Y-BOCS provided the optimal fit. We also found some support for a three-factor solution consistent with earlier findings by Kim et al. and Moritz et al. (Kim et al., 1994; Moritz et al., 2002). The produced factors showed good reliability and strong correlations with the Y-BOCS Total score. However, the resistance to compulsion item failed to demonstrate adequate correlation to the Total score, a finding consistent with earlier findings in several studies with patients with OCD.


A novel cohort of cancer-testis biomarker genes revealed through meta-analysis of clinical data sets.
The identification of cancer-specific biomolecules is of fundamental importance to the development of diagnostic and/or prognostic markers, which may also serve as therapeutic targets. Some antigenic proteins are only normally present in male gametogenic tissues in the testis and not in normal somatic cells. When these proteins are aberrantly produced in cancer they are referred to as cancer/testis (CT) antigens (CTAs). Some CTA genes have been proven to encode immunogenic proteins that have been used as successful immunotherapy targets for various forms of cancer and have been implicated as drug targets. Here, a targeted in silico analysis of cancer expressed sequence tag (EST) data sets resulted in the identification of a significant number of novel CT genes. The expression profiles of these genes were validated in a range of normal and cancerous cell types. Subsequent meta-analysis of gene expression microarray data sets demonstrates that these genes are clinically relevant as cancer-specific biomarkers, which could pave the way for the discovery of new therapies and/or diagnostic/prognostic monitoring technologies.


Cerebral dysfunction in fibromyalgia: evidence from regional cerebral blood flow measurements, otoneurological tests and cerebrospinal fluid analysis.
Measurements of regional cerebral blood flow (rCBF), analysis of cerebrospinal fluid, auditory brain stem responses (ABR) and oculomotor tests were performed in 19 patients with fibromyalgia. The results from the rCBF measurements showed a normal flow level with slight but significant focal flow decreases in dorsolateral frontal cortical areas of both hemispheres. The ABR results showed signs of dysfunction at least at the brain stem level and the oculomotor tests showed high frequency of pathology. The cerebrospinal fluid analysis showed discrete changes in the cell differential count. Possible explanations for the involvement of the central nervous system in fibromyalgia are discussed.


A catalog of genetic loci associated with kidney function from analyses of a million individuals.
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.


Global distribution of Chelonid fibropapilloma-associated herpesvirus among clinically healthy sea turtles.
Fibropapillomatosis (FP) is a neoplastic disease characterized by cutaneous tumours that has been documented to infect all sea turtle species. Chelonid fibropapilloma-associated herpesvirus (CFPHV) is believed to be the aetiological agent of FP, based principally on consistent PCR-based detection of herpesvirus DNA sequences from FP tumours. We used a recently described PCR-based assay that targets 3 conserved CFPHV genes, to survey 208 green turtles (Chelonia mydas). This included both FP tumour exhibiting and clinically healthy individuals. An additional 129 globally distributed clinically healthy individual sea turtles; representing four other species were also screened. CFPHV DNA sequences were obtained from 37/37 (100%) FP exhibiting green turtles, and 45/300 (15%) clinically healthy animals spanning all five species. Although the frequency of infected individuals per turtle population varied considerably, most global populations contained at least one CFPHV positive individual, with the exception of various turtle species from the Arabian Gulf, Northern Indian Ocean and Puerto Rico. Haplotype analysis of the different gene markers clustered the CFPHV DNA sequences for two of the markers (UL18 and UL22) in turtles from Turks and Caicos separate to all others, regardless of host species or geographic origin. Presence of CFPHV DNA within globally distributed samples for all five species of sea turtle was confirmed. While 100% of the FP exhibiting green turtles yielded CFPHV sequences, surprisingly, so did 15% of the clinically healthy turtles. We hypothesize that turtle populations with zero (0%) CFPHV frequency may be attributed to possible environmental differences, diet and/or genetic resistance in these individuals. Our results provide first data on the prevalence of CFPHV among seemingly healthy turtles; a factor that may not be directly correlated to the disease incidence, but may suggest of a long-term co-evolutionary latent infection interaction between CFPHV and its turtle-host across species. Finally, computational analysis of amino acid variants within the Turks and Caicos samples suggest potential functional importance in a substitution for marker UL18 that encodes the major capsid protein gene, which potentially could explain differences in pathogenicity. Nevertheless, such a theory remains to be validated by further research.


Tuning photoluminescence of organic rubrene nanoparticles through a hydrothermal process.
Light-emitting 5,6,11,12-tetraphenylnaphthacene (rubrene) nanoparticles (NPs) prepared by a reprecipitation method were treated hydrothermally. The diameters of hydrothermally treated rubrene NPs were changed from 100 nm to 2 μm, depending on hydrothermal temperature. Photoluminescence (PL) characteristics of rubrene NPs varied with hydrothermal temperatures. Luminescence of pristine rubrene NPs was yellow-orange, and it changed to blue as the hydrothermal temperature increased to 180°C. The light-emitting color distribution of the NPs was confirmed using confocal laser spectrum microscope. As the hydrothermal temperature increased from 110°C to 160°C, the blue light emission at 464 to approximately 516 nm from filtered-down NPs was enhanced by H-type aggregation. Filtered-up rubrene NPs treated at 170°C and 180°C exhibited blue luminescence due to the decrease of intermolecular excimer densities with the rapid increase in size. Variations in PL of hydrothermally treated rubrene NPs resulted from different size distributions of the NPs.


Investigating a suitable model for the study of vitamin D mediated regulation of human placental gene expression.
Transfer and metabolism of vitamin D across the human placenta is required for fetal development. However, these fundamental mechanisms are not well understood and model systems are required to help understand them. The BeWo choriocarcinoma cell line is derived from extravillous trophoblast but is used as a model for villous syncytiotrophoblast and the placental barrier. Questions have been raised about the suitability of the BeWo cell line as a model for villous trophoblast. This study compares the expression of amino acid transporters and vitamin D related genes in human term placenta with the BeWo and human embryonic kidney (HEK)293 cell lines. HEK293 cells, as transporting epithelium may be more similar to placenta. Gene expression in term placenta was much more similar to HEK293 than BeWo. This study provides further evidence that the BeWo cell line is not an appropriate model for villous trophoblast and a model that more closely represents the human placenta is now required to investigate the effects of vitamin D on the placenta ex-vivo.


Effect of polydispersity and soft interactions on the nematic versus smectic phase stability in platelet suspensions.
We theoretically discuss, using density-functional theory, the phase stability of nematic and smectic ordering in a suspension of platelets of the same thickness but with a high polydispersity in diameter, and study the influence of polydispersity on this stability. The platelets are assumed to interact like hard objects, but additional soft attractive and repulsive interactions, meant to represent the effect of depletion interactions due to the addition of nonabsorbing polymer, or of screened Coulomb interactions between charged platelets in an aqueous solvent, respectively, are also considered. The aspect (diameter-to-thickness) ratio is taken to be very high, in order to model solutions of mineral platelets recently explored experimentally. In this regime a high degree of orientational ordering occurs; therefore, the model platelets can be taken as completely parallel and are amenable to analysis via a fundamental-measure theory. Our focus is on the nematic versus smectic phase interplay, since a high degree of polydispersity in diameter suppresses the formation of the columnar phase. When interactions are purely hard, the theory predicts a continuous nematic-to-smectic transition, regardless of the degree of diameter polydispersity. However, polydispersity enhances the stability of the smectic phase against the nematic phase. Predictions for the case where an additional soft interaction is added are obtained using mean-field perturbation theory. In the case of the one-component fluid, the transition remains continuous for repulsive forces, and the smectic phase becomes more stable as the range of the interaction is decreased. The opposite behavior with respect to the range is observed for attractive forces, and in fact the transition becomes of first order below a tricritical point. Also, for attractive interactions, nematic demixing appears, with an associated critical point. When platelet polydispersity is introduced the tricritical temperature shifts to very high values.


Benign radiographic coronal synostosis after sagittal synostosis repair.
Whether cranial vault remodeling surgery for nonsyndromic, isolated sagittal suture synostosis affects the patency of initially normal, unaffected sutures is unknown. The influence of coronal and lambdoidal suture patency after cranial vault remodeling on the trajectory of subsequent cranial growth is also unknown. Disruption of normal sutural anatomy during cranial vault reconstruction could influence the incidence of secondary craniosynostosis and need for reoperation in a small proportion of these patients.We performed a retrospective review of patients younger than 1 year with nonsyndromic sagittal synostosis treated at a single tertiary referral pediatric hospital from September 2005 to January 2010 by an interdisciplinary team. Computed tomographic images obtained preoperatively, immediately postoperatively, and 2 years postoperatively were evaluated for the occurrence of secondary synostosis of initially nonsynostotic sutures. Craniofacial disorders clinic and ophthalmologic follow-up records were also analyzed for the occurrence of radiographic cranial restenosis, clinical or ophthalmologic signs of intracranial hypertension (ICH), and reoperation.Fifty-one patients younger than 1 year underwent primary surgical repair of isolated, nonsyndromic sagittal suture synostosis during the study period. Thirty-seven of these patients (71%) had completed 2-year clinical and radiographic follow-up by the time of analysis, constituting the study population. The average age at surgery was 5.4 months (range, 3.1-11.5 months). Thirty-three (89%) of the 37 study patients showed radiographic evidence of bilateral secondary coronal synostosis (SCS). Five patients (15%) additionally showed partial lambdoid synostosis. One patient with radiographic SCS (3%) required reoperation for radiographic cranial restenosis, clinical signs and symptoms of ICH, and papilledema first noted 1 year after primary cranial vault reconstruction.There is a high incidence of secondary coronal suture synostosis following cranial vault remodeling for isolated, nonsyndromic sagittal synostosis. Postoperative SCS was only rarely associated with secondary radiographic cranial stenosis, clinical or ophthalmologic signs of ICH, and the need for reoperation.


Nature and sources of poisoning in patients admitted to a referral hospital in Gaborone, Botswana; findings and implications.
Intentional poisoning is becoming an important public health concern particularly among young women globally. Consequently, there is a need to analyze this further within countries to establish pertinent policies to reduce current incidence rates. This includes sub-Saharan African countries where there has been a scarcity of information. Consequently, we sought to establish the nature and sources of poisoning in patients admitted to a leading hospital in Botswana to help develop pertinent future policies for Botswana and surrounding countries. Retrospectively reviewing the medical records of all patients admitted to Princess Marina Hospital (PMH), which is a leading tertiary hospital in the capital city of Botswana, due to acute poisoning over a six-year period. The records for 408 patients were reviewed. The majority of admissions (58%) were females, and the mean age of patients was 21(±14) years. Most poisoning cases (53%) were intentional. The 15-45 years age group was most likely to intentionally poison themselves compared to other age groups, with females four and half times more likely to intentionally poison themselves compared to males (AOR 4.53, 95% CI: 2.68-7.89, p < 0.001). Half of the patients were poisoned by medicines followed by household chemicals (22%), with females overall four times more likely to be poisoned by medicines compared to males. The medicine mostly ingested was paracetamol (30%). Failing relationships (57%) were the principal reason for intentional poisoning. Six patients died from poisoning representing a 1.5% mortality rate. The findings suggest in-depth and urgent investigations on intentional poisoning are needed among young women across countries including sub-Saharan African countries to inform future policies on prevention strategies. Further, strategies for poisoning prevention should target social and family relationship problems. We will be following this up in the future.


Lumbar spinal stenosis is a highly genetic condition partly mediated by disc degeneration.
Objective. Lumbar spinal stenosis is one of the most commonly diagnosed spinal disorders in older adults. Although the pathophysiology of the clinical syndrome is not well understood, a narrow central canal or intervertebral foramen is an essential or defining feature. The aim of the present study was to estimate the magnitude of genetic versus environmental influences on central lumbar spinal stenosis and to investigate disc degeneration and stature or bone development as possible genetic pathways.Methods. A classic twin study with multivariate analyses considering lumbar level and other covariates was conducted. The study sample comprised 598 male twins (147 monozygotic and 152 dizygotic pairs), 35-70 years of age, from the population-based Finnish Twin Cohort. The primary phenotypes were central lumbar stenosis as assessed qualitatively on magnetic resonance imaging (MRI) and quantitatively measured dural sac cross-sectional area. Additional phenotypes (to examine possible genetic pathways) included disc bulging and standing height, as an indicator of overall skeletal size or development.Results. The heritability estimate (h²) for qualitatively assessed central lumbar spinal stenosis on MRI was 66.9% (95% confidence interval [95% CI] 56.8,74.5). The broad-sense heritability estimate for dural sac cross-sectional area was 81.2% (95% CI 74.5, 86.1),with a similar magnitude of genetic influences across lumbar levels (h²=72.4–75.6). The additive genetic correlation of quantitatively assessed stenosis and disc bulging was extremely high. There was no indication of shared genetic influences between stenosis and stature.Conclusion. Central lumbar spinal stenosis and associated dural sac dimensions are highly genetic, and disc degeneration (bulging) appears to be one pathway through which genes influence spinal stenosis.


Temporal Bone CT: Improved Image Quality and Potential for Decreased Radiation Dose Using an Ultra-High-Resolution Scan Mode with an Iterative Reconstruction Algorithm.
Radiation dose in temporal bone CT imaging can be high due to the requirement of high spatial resolution. In this study, we assessed whether CT imaging of the temporal bone by using an ultra-high-resolution scan mode combined with iterative reconstruction provides higher spatial resolution and lower image noise than a z-axis ultra-high-resolution mode. Patients with baseline temporal bone CT scans acquired by using a z-axis ultra-high-resolution protocol and a follow-up scan by using the ultra-high-resolution-iterative reconstruction technique were identified. Images of left and right temporal bones were reconstructed in the axial, coronal, and Poschl planes. Three neuroradiologists assessed the spatial resolution of the following structures: round and oval windows, incudomallear and incudostapedial joints, basal turn spiral lamina, and scutum. The paired z-axis ultra-high-resolution and ultra-high-resolution-iterative reconstruction images were displayed side by side in random order, with readers blinded to the imaging protocol. Image noise was compared in ROIs over the posterior fossa. We identified 8 patients, yielding 16 sets of temporal bone images (left and right). Three sets were excluded because the patient underwent surgery between the 2 examinations. Spatial resolution was comparable (Poschl) or slightly better (axial and coronal planes) with ultra-high-resolution-iterative reconstruction than with z-axis ultra-high-resolution. A paired t test indicated that noise was significantly lower with ultra-high-resolution-iterative reconstruction than with z-axis ultra-high-resolution (P < .001), with a mean noise reduction of 37% (range, 18%-49%). The ultra-high-resolution-iterative reconstruction scan mode has similar or slightly better resolution relative to the z-axis ultra-high-resolution mode for CT of the temporal bone but significantly (P < .01) lower image noise, which may enable the dose to be reduced by approximately 50%.