Tropical neuroinfections in south sudanese rural hospitals - analysis of 8,709 patients.
Infections involving the central nervous system have very serious consequences and affect thousands of people in Africa. Despite the availability of new antibiotics and vaccines, neuroinfections act as dangerous and life-threatening conditions. The most frequent neuroinfections which are of the greatest importance for public health systems are viral diseases (such as HIV, encephalitis, poliomyelitis, rabies), bacterial diseases (bacterial meningitis, neurological complications of leprosy and tuberculosis) and parasitic infections (cerebral malaria, sleeping sickness, trypanosomiasis, schistosomiasis, toxoplasmosis etc.). A descriptive study to assess the occurrence of neuroinfections in two rural hospitals in Sudan (Mapuordit in Yirol and Gordim in Aweil) was performed in two periods of two years: (i) 2005-2006 and (ii) 2010-2011. We obtained data on patients from Mapuordit and from Gordim by studying their medical records. Several cases of neuroinfections were observed during both periods; those were represented by tetanus, meningococcal meningitis, leprosy with neuropathy (altogether 442 patients) in Mapuordit. Also in Gordim, severe neuroinfections such as cerebral malaria were very rare (1 case), as well as tetanus (1 case), meningococcal meningitis (8 cases) and sleeping sickness (9 cases). However, the incidence of neuroinfections decreased from 44/1000 in 2005-2006 to 2/1000 in 2010-2011. Decreased incidence of serious neuroinfections (cerebral malaria, sleeping sickness, meningococcal meningitis) in Sudan may be related to improvement of effective therapeutic options, represented by (i) intermittent preventive therapy (IPT) for malaria, (ii) by suppression of sleeping sickness vectors and (iii) by better accessibility of antibiotics.


Conservative management of elemental mercury retained in the appendix.
Few cases of mercury sequestration in the appendix appear in the literature. Based on these, both prophylactic appendectomy and non-surgical management have been recommended. We report a case in which a patient with mercury retained in the appendix was managed conservatively without developing mercurialism or appendicitis. A 43-year-old man ingested approximately one tablespoon of elemental mercury after an argument with his wife. An initial abdominal radiograph showed mercury in the pylorus of the stomach and a follow-up x-ray at 72 hours showed mercury localized to the appendix. The patient was treated as an outpatient and examined several times over a 37-day period. He never developed signs of appendicitis. On a follow-up examination 7 months after the ingestion, he was radiographically free of mercury. Periodically throughout his clinical course, blood mercury levels were obtained. Only one, 6 days after ingestion, showed an elevated mercury level of 68 mcg/L (reference range <10 mcg/L). Despite this, the patient never developed signs or symptoms of mercury poisoning. Patients in whom elemental mercury is retained in the appendix, who are without symptoms and have normal gastric mucosa, may be conservatively managed without surgery.


Hemodialysis vascular accesses in patients on chronic hemodialysis at the Kenyatta National Hospital in Kenya.
The objective of our study was to document the level of preparedness for renal replacement therapy assessed by incident hemodialysis vascular access and the access at least 3 months after initiation of hemodialysis at Kenyatta National Hospital, Nairobi. Between June and July 2018, we carried out a cross-sectional descriptive study on the preparedness for hemodialysis by patients who were on chronic hemodialysis in the Kenyatta National Hospital Renal Department. Sociodemographic, medical history, duration of follow-up, and state of preparedness parameters were obtained through interview and entered into the questionnaire. The data were entered in preprogrammed format in the Statistical Package for the Social Sciences (SPSS) version 20.0 for analyses. Eighty-two patients were enrolled. Males were 50% (41). The mean age was 45.39 ± 15.96 years but females were 5 years younger than their male counterparts. About 85.4% of the patients were drawn from the hypertension and diabetes clinics, and the mean, mode, and median of the duration of follow-up were 41, 0, and 0 months, respectively, in these clinics. Almost three in every four patients (74.4%) were initiated on hemodialysis as emergency (p value < 0.001). About 80% were initiated hemodialysis via acute catheters placed in the jugular and subclavian veins (p value < 0.001). At least 3 months later, 40% still had acute catheters on the same veins (p value < 0.001). Acute venous catheters in the femoral veins were in 9.2% at initiation and 6.6% of the patients at least 3 months later. Less than 2% of the patients had arteriovenous fistulae at initiation, which rose to 14.5% in 3 months. Tunneled catheters were placed in 11.8% initially and at least 3 months, were almost in 40% of the patients. In conclusion, our young hemodialysis population mainly drawn from hypertension and diabetes clinic requires more input in hemodialysis vascular access planning. Focused individualized follow-up and early referrals to nephrologists are required. Uptake of arteriovenous grafts for hemodialysis might reduce the prevalence of hemodialysis catheters. As it is, this population is threatened with iterative vascular accesses complications as well as real danger of exhaustion of their vascular capital. There is real danger of increase in mortality from access complications.


Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study.
The Third National Wilms' Tumor Study sought to reduce treatment for low-risk patients and find better chemotherapy for those at high risk for relapse. Eligible patients (1439) were randomized according to stage (I-IV) and histology (favorable [FH] or unfavorable [UH]), and contributed data to survival and relapse-free survival (RFS) analyses. Four-year (postnephrectomy) survival percentages and randomized treatment regimens for low-risk patients were 96.5% for 607 Stage I/FH patients who received dactinomycin (Actinomycin D [AMD], Merck Sharp & Dohme, West Point, PA) and vincristine (VCR) for 10 weeks versus 6 months; 92.2% for 278 Stage II/FH patients; and 86.9% for 275 Stage III/FH patients who received AMD + VCR +/- Adriamycin (ADR, Adria Laboratories, Columbus, OH) for 15 months. Stage II/FH patients also had either zero or 2000 cGy irradiation (RT) postoperatively and Stage III/FH patients either 1000 or 2000 cGy. Four-year survival was 73.0% for 279 high-risk patients (any Stage IV, all UH) who received postoperative radiation therapy (RT) and AMD + VCR + ADR +/- cyclophosphamide (CPM). Statistical analysis of survival and RFS experience shows that the less intensive therapy does not worsen results for low-risk patients and CPM does not benefit those at high risk.


Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.
The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.


Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial.
Progressive resistance exercise training (PRT) has been shown to increase muscle strength and fat-free mass (FFM) in elderly persons. Limited information is available regarding the effects of PRT on lean and fat mass in frail elderly persons. Ninety-one community-dwelling sedentary men and women, 78 years and older with physical frailty (defined using standardized objective criteria) were enrolled in a 9-month trial of exercise training (ET). Physical frailty was defined as having 2 of the 3 following criteria: modified Physical Performance Test score between 18 and 32, peak aerobic power between 10 and 18 ml/kg/min, or self-report of difficulty or assistance with two instrumental activities of daily living or one basic activity of daily living. Participants were randomly assigned to either a control (CTL) group that performed a low intensity home exercise program or a supervised ET group that performed 3 months of low intensity exercise and 3 months of PRT. After completion of PRT, ET participants had greater improvements than did CTL participants in maximal voluntary force production for knee extension (mean Delta +5.3 +/- 13 ft/lb vs +1.1 +/- 11 ft/lb, p =.05), measured using isokinetic dynamometry. Total body FFM (measured using dual energy x-ray absorptiometry) increased in the ET group, but not in the CTL group (mean Delta +0.84 +/- 1.4 kg vs +0.01 +/- 1.5 kg, p =.005). Total, trunk, intra-abdominal, and subcutaneous fat mass (measured using dual energy x-ray absorptiometry and (1)H-magnetic resonance imaging) did not change in response to PRT. Three months of supervised PRT induced improvements in maximal voluntary thigh muscle strength and whole body FFM in frail, community-dwelling elderly women and men. This supervised exercise program may not be sufficient to reduce whole-body or intra-abdominal fat area in this population.


Chromosomal behavior in starfish (Asterina pectinifera) zygotes under the effect of aphidicolin, an inhibitor of DNA polymerase.
When calf thymus histones were labeled fluorescently and microinjected into oocytes of the starfish, Asterina pectinifera, the labeled histones visualized chromosomes during maturation division and cleavage. In doing so, we confirmed the previously reported phenomenon that chromosomes became incompetent at the first cleavage in the aphidicolin-treated egg, although cleavage itself took place. Moreover, we found that chromosomes were aligned at the equator of the metaphase spindle of the first cleavage and that they did not separate into two groups at all, but made a lump in the middle of the spindle. Chromosomes finally entered one blastomere, although they did not participate in the following karyokinesis. DNA and microtubules were examined by cytochemistry and immunofluorescence in order to investigate the relation between chromosome movement and the microtubular cytoskeleton. The mitotic apparatus developed and grew in the aphidicolin-treated cells in the same manner as those in normal cells without normal chromatin condensation or chromosome movement during the first cleavage. However, the mitotic apparatus consisted of two asters without the spindle formed at subsequent cleavages. Electron microscopic study revealed that chromosomes did not condense normally and kinetochores were not detected during the first cleavage. These results indicate that the dynamic changes in microtubular structures during mitosis have poor relation with the chromosome behavior such as prophase chromosome condensation and anaphase chromosome movement.


Simvastatin prodrug micelles target fracture and improve healing.
Simvastatin (SIM), a widely used anti-lipidemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. In this study, an amphiphilic macromolecular prodrug of SIM was designed and synthesized to overcome these limitations. The polyethylene glycol (PEG)-based prodrug can spontaneously self-assemble to form micelles. The use of SIM trimer as the prodrug's hydrophobic segment allows easy encapsulation of additional free SIM. The in vitro studies showed that SIM/SIM-mPEG micelles were internalized by MC3T3 cells via lysosomal trafficking and consistently induced expression of both BMP2 and DKK1 mRNA, suggesting that the prodrug micelle retains the biological functions of SIM. After systemic administration, optical imaging suggests that the micelles would passively target to bone fracture sites associated with hematoma and inflammation. Furthermore, flow cytometry study revealed that SIM/SIM-mPEG micelles had preferred cellular uptake by inflammatory and resident cells within the fracture callus tissue. The treatment study using a mouse osteotomy model validated the micelles' therapeutic efficacy in promoting bone fracture healing as demonstrated by micro-CT and histological analyses. Collectively, these data suggest that the macromolecular prodrug-based micelle formulation of SIM may have great potential for clinical management of impaired fracture healing.


An overview of the reclassification of COVID-19 of the Infectious Diseases Control Law in Japan.
Japan's responses to COVID-19 have been conducted based on the Act on the Prevention of Infectious Diseases and Medical Care for Patients with Infectious Diseases (the Infectious Diseases Control Law) and the Act on Special Measures against Novel Influenza, etc. (the Act on Special Measures), as COVID-19 is classified as the category of "the Novel Influenza etc." under the Infectious Diseases Control Law. The government's Novel Coronavirus Response Headquarters decided to reclassify COVID-19 as a Category V infectious disease under the Infectious Diseases Control Law in May 2023 since the disease has become less lethal. Accordingly, the countermeasures such as surveillance and medical care are going to be reviewed, and COVID-19 prevention actions will depend on personal choices (Prior to the review in May, mask usage will be changed from 13 March). However, this does not mean that infection control measures are no longer necessary; it is recommended that such measures be taken in certain settings in order to prevent the elderly and those who at a high risk of severe illness from being infected, even after the disease is classified as Category V.


A high-resolution dynamic probabilistic material flow analysis of seven plastic polymers; A case study of Norway.
Plastic pollution has long been identified as one of the biggest challenges of the 21st century. To tackle this problem, governments are setting stringent recycling targets to keep plastics in a closed loop. Yet, knowledge of the stocks and flows of plastic has not been well integrated into policies. This study presents a dynamic probabilistic economy-wide material flow analysis (MFA) of seven plastic polymers (HDPE, LDPE, PP, PS, PVC, EPS, and PET) in Norway from 2000 to 2050. A total of 40 individual product categories aggregated into nine industrial sectors were examined. An estimated 620 ± 23 kt or 114 kg/capita of these seven plastic polymers was put on the Norwegian market in 2020. Packaging products contributed to the largest share of plastic put on the market (∼40%). The accumulated in-use stock in 2020 was about 3400 ± 56 kt with ∼60% remaining in buildings and construction sector. In 2020, about 460 ± 22 kt of plastic waste was generated in Norway, with half originating from packaging. Although ∼50% of all plastic waste is collected separately from the waste stream, only around 25% is sorted for recycling. Overall, ∼50% of plastic waste is incinerated, ∼15% exported, and ∼10% landfilled. Under a business-as-usual scenario, the plastic put on the market, in-use stock, and waste generation will increase by 65%, 140%, and 90%, respectively by 2050. The outcomes of this work can be used as a guideline for other countries to establish the stocks and flows of plastic polymers from various industrial sectors which is needed for the implementation of necessary regulatory actions and circular strategies. The systematic classification of products suitable for recycling or be made of recyclate will facilitate the safe and sustainable recycling of plastic waste into new products, cap production, lower consumption, and prevent waste generation.


DiGeorge's or the III-IV pharyngeal pouch syndrome: pathology and a theory of pathogenesis.
Six new cases of the III-IV pharyngeal pouch syndrome were encountered at autopsy among 897 consecutive pediatric autoposies. All occurred in patients with conotruncal cardiac anomalies. The anatomic characteristics of the heart defect suggest a possible mechanism for the pathogenesis of this developmental anomaly. It is postulated that premature involution of the thyroidea ima artery, which is the principal embryonic blood source to the 3rd and 4th pharyngeal pouches and the ultimobranchial body, may be the critical event in the embryogenesis of the syndrome. Hemodynamic alterations in the course of anomalous morphogenesis of conotruncal anomalies may favor premature involution of certain vessels including the left 4th aortic arch and the thyroidea ima. Deficiencies of thymus, parathyroid glands and ultimobranchial tissue ("C" cells) may be the consequence of vascular deprivation during embryogenesis. These cases are discussed with regard to the proposed mechanism of pathogenesis and the influence of varying quantities of thymus upon peripheral lymphoid tissue. Both embryologic and clinical data support the possibility of a deficiency of ultimobranchial tissue. The range of minor and inconstant anomalies seen in patients with this syndrome is presented.


Moderate-intensity exercise training reduces vasorelaxation of mesenteric arteries: role of BKCa channels and nitric oxide.
Exercise training (ET) is well established to induce vascular adaptations on the metabolically active muscles. These adaptations include increased function of vascular potassium channels and enhanced endothelium-dependent relaxations. However, the available data on the effect of ET on vasculatures that normally constrict during exercise, such as mesenteric arteries (MA), are scarce and not conclusive. Therefore, this study hypothesized that 10 weeks of moderate-intensity ET would result in adaptations towards more vasoconstriction or/and less vasodilatation of MA. Young Fischer 344 rats were randomly assigned to a sedentary group (SED; n=24) or exercise training group (EXE; n=28). The EXE rats underwent a progressive treadmill ET program for 10 weeks. Isometric tensions of small (SED; 252.9+/-29.5 microm, EXE; 248.6+/-34.4 microm) and large (SED; 397.7+/-85.3 microm, EXE; 414.0+/-86.95 microm) MA were recorded in response to cumulative phenylephrine concentrations (PE; 0-30 microM) in the presence and absence of the BKCa channel blocker, Iberiotoxin (100 nM). In another set of experiments, tensions in response to cumulative concentration-response curves of acetylcholine (ACh) or sodium nitroprusside (SNP) were obtained, and pEC50s were compared. Immunoblotting was performed to measure protein expression levels of the BKCa channel subunits and eNOS. ET did not alter the basal tension of small and large MA but significantly increased their responses to PE, and reduced the effect of BKCa channels in opposing the contractile responses to PE without changes in the protein expression level of BKCa subunits. ET also elicited a size-dependent functional adaptations that involved reduced endothelium-independent and endothelium-dependent relaxations. In large MA the sensitivity to SNP was decreased more than in small MA suggesting impaired nitric oxide (NO)-dependent mechanisms within the vascular smooth muscle cells of ET group. Whereas the shift in pEC50 of ACh-induced relaxation of small MA would suggest more effect on the production of NO within the endothelium, which is not changed in large MA of ET group. However, the eNOS protein expression level was not significantly changed between the ET and SED groups. In conclusion, our results indicate an increase in contraction and reduced relaxation of MA after 10 weeks of ET, an adaptation that may help shunt blood flow to metabolically active tissues during acute exercise.


The forced swim test has poor accuracy for identifying novel antidepressants.
Despite the prevalence of treatment-resistant depression, many pharmaceutical companies have abandoned the development of new antidepressants. Experts have attributed this, in part, to the low quality of preclinical tests available in this field, often citing over-reliance on animal behavioral screens, such as the forced swim test (FST). This retrospective review assessed whether compounds tested in the FST by major pharmaceutical companies were shown to have antidepressant effects in humans. Of 109 compounds identified, only 28% had been explored for antidepressant effects in humans. Of these, there were only three for which the FST appeared to positively predict antidepressant efficacy, but none are currently approved to treat any type of depression. With such poor accuracy for identifying novel antidepressants, the FST might not be a useful screening tool for this purpose.


An unusual membrane system in the oocyte of the ascidian Botryllus schlosseri.
During vitellogenesis, oocytes of Botryllus schlosseri always exhibit an unusual system scattered in the cytoplasm. It consists of an association between a single fenestrated endoplasmic reticulum cisterna and one or a few smooth vesicles (cisterna vesicle association: CVA) containing a dense core facing the cisterna itself. The latter is smooth and perforated by numerous small pores (about 25 nm in diameter) in the area of association; towards the periphery, it extends into several branches with ribosomes bound to their membranes. In the vesicles, fibrillar material radiates from the dense core and is sometimes organized into a long, dense lamina. The membranes of both cisterna and vesicles appear to be coupled, but are in fact separated by a constant narrow space occupied by short densities. The presence in B. schlosseri of this unusual fenestrated membrane system contrasts with the absence of a typical porous cytoplasmic organelle, the annulate lamellae (ALs), which is widely distributed in female gametes. However, as in other animals, B. schlosseri oocytes possess intranuclear annulate lamellae (IALs) and vesicles. Comparative observations extended to the oocytes of the ascidian Ciona intestinalis have shown that the latter species exhibits typical ALs and IALs, but not the CVA. The morphology of the CVA is analysed here in detail, and similarities and differences with ALs are pointed out. Hypotheses regarding CVA function are discussed in terms of possible relations with ALs.


Greenhouse gas emissions from operating reserves used to backup large-scale wind power.
Wind farms provide electricity with no direct emissions. However, their output cannot be forecasted perfectly, even a short time ahead. Consequently, power systems with large amounts of wind power may need to keep extra fossil-fired generators turned on and ready to provide power if wind farm output drops unexpectedly. In this work, I introduce a new model for estimating the uncertainty in short-term wind power forecasts, and how this uncertainty varies as wind power is aggregated over larger regions. I then use this model to estimate the reserve requirements in order to compensate for wind forecast errors to a 99.999% level of reliability, and an upper limit on the amount of carbon dioxide that would be emitted if natural gas power plants are used for this purpose. I find that for regions larger than 500 km across, operating reserves will undo 6% or less of the greenhouse gas emission savings that would otherwise be expected from wind power.


Tracking local conformational changes of ribonuclease A using picosecond time-resolved fluorescence of the six tyrosine residues.
The six tyrosine residues of ribonuclease A (RNase A) are used as individual intrinsic probes for tracking local conformational changes during unfolding. The fluorescence decays of RNase A are well described by sums of three exponentials with decay times (tau(1) = 1.7 ns, tau(2) = 180 ps, and tau(3) = 30 ps) and preexponential coefficients (A(1) = 1, A(2) = 1, and A(3) = 4) at pH 7, 25 degrees C. The decay times are controlled by photo-induced electron transfer from individual tyrosine residues to the nearest disulphide (-SS-), bridge, which is distance (R) dependent. We assign tau(1) to Tyr-76 (R = 12.8 A), tau(2) to Tyr-115 (R = 6.9 A), and tau(3) to Tyr-25, Tyr-73, Tyr-92, and Tyr-97 (all four at R = 5.5 +/- 0.3 A) at 23 degrees C. On the basis of this assignment, the results show that, upon thermal or chemical unfolding only Tyr-25, Tyr-92, and Tyr-76 undergo significant displacement from their nearest -SS- bridge. Despite reporting on different regions of the protein, the concordance between the transition temperatures, T(m), obtained from Tyr-76 (T(m) = 59.2 degrees C) and Tyr-25 and Tyr-92 (T(m) = 58.2 degrees C) suggests a single unfolding event in this temperature range that affects all these regions similarly.


Modified MRI Anonymization (De-Facing) for Improved MEG Coregistration.
Localising the sources of MEG/EEG signals often requires a structural MRI to create a head model, while ensuring reproducible scientific results requires sharing data and code. However, sharing structural MRI data often requires the face go be hidden to help protect the identity of the individuals concerned. While automated de-facing methods exist, they tend to remove the whole face, which can impair methods for coregistering the MRI data with the EEG/MEG data. We show that a new, automated de-facing method that retains the nose maintains good MRI-MEG/EEG coregistration. Importantly, behavioural data show that this "face-trimming" method does not increase levels of identification relative to a standard de-facing approach and has less effect on the automated segmentation and surface extraction sometimes used to create head models for MEG/EEG localisation. We suggest that this trimming approach could be employed for future sharing of structural MRI data, at least for those to be used in forward modelling (source reconstruction) of EEG/MEG data.


From orbitals to observables and back.
Molecular orbital framework is of central importance in chemistry. Often used by chemists and physicists to gain insight into molecular properties, Hartree-Fock or Kohn-Sham orbitals are obtained from rather crude treatments and, strictly speaking, are not observables. Yet, quantum mechanics offers a route for connecting general many-electron wavefunctions with reduced quantities-density matrices and orbitals-which give rise to observable properties. Such mapping makes possible, in principle, reconstruction of these objects from sufficiently detailed experimental data. This Perspective discusses Dyson orbitals and various types of natural transition orbitals and illustrates their role in modeling and interpreting different types of spectroscopic measurements.


Advances in prostate cancer imaging.
Many exciting advances in medical imaging have been made in recent years that will alter the way we diagnose, stage, and treat patients with prostate cancer. Multiparametric magnetic resonance imaging (MRI) is emerging as the main modality for prostate cancer imaging. Contrast-enhanced ultrasound and shear wave elastography may be strong alternatives in patients who cannot undergo MRI. Prostate-specific membrane antigen-directed positron emission tomography/computed tomography has proven to be valuable in the primary staging of high-risk disease and for detecting disease in patients with biochemical recurrence. As more studies continue to emerge, it is becoming clear that the standard algorithm for diagnosing and staging prostate cancer will undergo significant changes in the near future.


A comparative study of processing simulated and experimental data in elastic laser light scattering.
The intensity of the laser light scattered by a suspension of biological particles undergoing Brownian motion contains information about their size distribution function and optical properties. We used several methods (implemented in MathCAD programs), including a new one, to invert the Fredholm integral equation of the first kind, which represents the angular dependence of the elastic scattering of light. The algorithms were first tested on different sets of simulated data. Experimental data were obtained using biological samples and an experimental arrangement which are briefly described. We study the stability of the inversion procedures relative to the noise levels, and compute the first two moments of the retrieved size distribution function. A comparison of the results corresponding to simulated and experimental data is done, to select the best processing algorithm.


Mean-field description and propagation of chaos in networks of Hodgkin-Huxley and FitzHugh-Nagumo neurons.
We derive the mean-field equations arising as the limit of a network of interacting spiking neurons, as the number of neurons goes to infinity. The neurons belong to a fixed number of populations and are represented either by the Hodgkin-Huxley model or by one of its simplified version, the FitzHugh-Nagumo model. The synapses between neurons are either electrical or chemical. The network is assumed to be fully connected. The maximum conductances vary randomly. Under the condition that all neurons' initial conditions are drawn independently from the same law that depends only on the population they belong to, we prove that a propagation of chaos phenomenon takes place, namely that in the mean-field limit, any finite number of neurons become independent and, within each population, have the same probability distribution. This probability distribution is a solution of a set of implicit equations, either nonlinear stochastic differential equations resembling the McKean-Vlasov equations or non-local partial differential equations resembling the McKean-Vlasov-Fokker-Planck equations. We prove the well-posedness of the McKean-Vlasov equations, i.e. the existence and uniqueness of a solution. We also show the results of some numerical experiments that indicate that the mean-field equations are a good representation of the mean activity of a finite size network, even for modest sizes. These experiments also indicate that the McKean-Vlasov-Fokker-Planck equations may be a good way to understand the mean-field dynamics through, e.g. a bifurcation analysis.Mathematics Subject Classification (2000): 60F99, 60B10, 92B20, 82C32, 82C80, 35Q80.


Steroid-Induced Psychosis in the Pediatric Population: A New Case and Review of the Literature.
Iatrogenic steroid-induced psychosis is a rare but serious adverse side effect seen largely in the adult population that less commonly affects children and adolescents. Given the significant distress steroid-induced psychosis may cause, recommendations are needed for effective management. Here we conducted a systematic review of the literature and report a new case of steroid-induced psychosis in a 12-year-old patient. We performed a systematic search using Embase, PubMed, Scopus, and PsychInfo. Key terms included ("steroid induced" or "corticosteroid induced" or "glucocorticoid induced") and ("psychosis" or "hallucinations" or "delusions") and ("child" or "adolescent" or "pediatric"). A total of 15 articles of steroid-induced psychosis in children and adolescents were found in the scientific literature. This report includes those articles and a novel case of steroid-induced psychosis. Children with asthma, autoimmune diseases, and cancer have been reported to experience steroid-induced psychosis. The mean age of children with steroid-induced psychosis was 12 ± 3.6 years. Our team presents a report of steroid-induced psychosis in a 12-year-old patient with discoid-type lupus erythematosus. Within days of treatment with 40 mg prednisone daily, this patient began to drool, became mute, and was responding to internal stimuli. Treatment was difficult secondary to the acute exacerbation of lupus, requiring ongoing therapy. It was initially unclear whether the acute psychosis was a manifestation of lupus, a side effect of medication, or a combination of the two risk factors. Neurology consultation ruled out lupus cerebritis. Psychosis was treated with haloperidol 5 mg. Psychosis did not resolve until the steroid taper was complete and the patient was no longer taking any prednisone. Given the common use of glucocorticoid therapy in children, it is important that physicians and parents recognize the signs of steroid-induced psychosis and are aware of the data on treating this complication.


Thermography in the determination of amputation levels in ischaemic limbs.
The reliability of thermography for the determination of the level of amputation for an ischaemic lower limb was compared with that of the doppler flowmeter and the clinical judgement of an experienced surgeon. The results showed that thermography tended to overestimate the degree of ischaemia and to indicate a higher level of amputation than was necessary. The advantages and the limitations of each method are discussed. It is concluded that the clinical judgement of the surgeon was the most reliable method and that the other investigations are only an adjunct to clinical assessment.


Milt production in goldfish: regulation by multiple social stimuli.
Previous studies in goldfish (Carassius auratus) demonstrate that milt (sperm and seminal fluid) volume is increased both by a preovulatory steroidal pheromone, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P), that acts by increasing serum concentrations of gonadotropin II (GTH-II), and by a post-ovulatory prostaglandin (PG) pheromone, that acts by stimulating sexual interactions. Here, we show that male goldfish also increase milt volume when isolated for 24 h, or when placed with another male injected with human chorionic gonadotropin (hCG) for 12 h. In contrast to the milt increase induced by pheromonal 17,20 beta-P, the milt increase following isolation or exposure to hCG-injected males was not associated with increased serum GTH-II. Serum growth hormone also was unaffected, although serum testosterone increased in isolated males. The absence of GTH-II increase following isolation or exposure to hCG-injected males and the long latency time for these two types of responses, suggests these effects are mediated by a novel mechanism as yet undescribed. The present findings suggest that sperm competition has selected for complex mechanisms regulating milt production and fertility in goldfish: males regulate milt production not only in response to stimulatory pheromonal cues from ovulatory females, but also in response to unknown stimulatory and inhibitory cues from male competitors.


Chondrotoxicity of ciprofloxacin in immature beagle dogs: immunohistochemistry, electron microscopy and drug plasma concentrations.
The systemic effects of ciprofloxacin in immature Beagles were studied. Dogs of 10-11 weeks were dosed orally for 5 days with 0 (n=3), 30 (n=5) and 200 (n=5) mg ciprofloxacin/kg body wt. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) 1 h after dosing (assuming to be peak concentrations). In view of the high doses used, the plasma concentrations were rather low and declined during the study period. For example, plasma concentrations in the high dose group were 6.6 +/- 0.9 mg/l (day 1), 3.9 +/- 1.4 mg/l (day 3), and 2.6 +/- 1.6 mg/l (day 5). In control dogs and in dogs treated with the low dose of ciprofloxacin no pathological changes were seen by light microscopy. However, cleft formation and erosions were observed in joint cartilage from two of five dogs treated with 200 mg/kg. It is noteworthy that despite the high dose used cartilage lesions were not detectable in all five dogs of this group by light microscopy. Using antibodies against cell membrane receptors (e.g. the alpha(5)beta(1)-integrin) or matrix components (fibronectin, collagen II) the articular cartilage effects were studied in detail by immunohistochemistry. The most sensitive alteration was an increase in fibronectin which was detectable in the vicinity of the lesions in cartilage samples from the group of dogs administered the high dose. No clear-cut changes were seen with the use of antibodies against other matrix components. Electron microscopy revealed typical alterations in chondrocytes from dogs treated with ciprofloxacin: e.g., swollen mitochondria and enlarged rough endoplasmic reticulum. These changes were much more pronounced in dogs from the high dose group than in dogs from the low dose group. Our main conclusion is that after oral administration ciprofloxacin exhibits rather low chondrotoxicity, even in the most sensitive species known to date. This correlates with the findings in humans that ciprofloxacin seems to be less chondrotoxic than pefloxacin or other quinolones.


An Effective Bundled Approach Reduces Surgical Site Infections in a High-Outlier Colorectal Unit.
Surgical site infections are the most common hospital-acquired infection after colorectal surgery, increasing morbidity, mortality, and hospital costs. The purpose of this study was to investigate the impact of preventive measures on colorectal surgical site infection rates in a high-volume institution that performs inherent high-risk procedures. This was a prospective cohort study. The study was conducted at a high-volume, specialized colorectal surgery department. The Prospective Surgical Site Infection Prevention Bundle Project included 14 preoperative, intraoperative, and postoperative measures to reduce surgical site infection occurrence after colorectal surgery. Surgical site infections within 30 days of the index operation were examined for patients during the 1-year period after the surgical site infection prevention bundle was implemented. The data collection and outcomes for this period were compared with the year immediately before the implementation of bundle elements. All of the patients who underwent elective colorectal surgery by a total of 17 surgeons were included. The following procedures were excluded from the analysis to obtain a homogeneous patient population: ileostomy closure and anorectal and enterocutaneous fistula repair. Surgical site infection occurring within 30 days of the index operation was measured. Surgical site infection-related outcomes after implementation of the bundle (bundle February 2014 to February 2015) were compared with same period a year before the implementation of bundle elements (prebundle February 2013 to February 2014). Between 2013 and 2015, 2250 abdominal colorectal surgical procedures were performed, including 986 (43.8%) during the prebundle period and 1264 (56.2%) after the bundle project. Patient characteristics and comorbidities were similar in both periods. Compliance with preventive measures ranged between 75% and 99% during the bundle period. The overall surgical site infection rate decreased from 11.8% prebundle to 6.6% at the bundle period (P < 0.001). Although a decrease for all types of surgical site infections was observed after the bundle implementation, a significant reduction was achieved in the organ-space subgroup (5.5%-1.7%; P < 0.001). We were unable to predict the specific contributions the constituent bundle interventions made to the surgical site infection reduction. The prospective Surgical Site Infection Prevention Bundle Project resulted in a substantial decline in surgical site infection rates in our department. Collaborative and enduring efforts among multiple providers are critical to achieve a sustained reduction See Video Abstract at http://links.lww.com/DCR/A438.


[Electric conductivity of lipid membranes in the presence of proteolytic enzymes and their substrates].
It is shown that there are spasmodic changes of electroconductivity in bimolecular membranes in the presence of alpha-chimotripsin and denatured ovalbumin or glycyl-d,L-beta-phenylalanine. These conductivity changes are not due to the interaction ob proteolysis products with lipid bilayer but result from the interaction of alpha-chimo trypsin with the substrate or competing inhibitor. Probability of the state with a specific conductivity depends on the membrane voltage. A modified membrane has a low ionic selectivity.


Recent advances in the social and behavioral aspects of filariasis.
Despite an increased awareness of the significance of social and behavioral influences upon various aspects of filariasis, there has been a relative lack of research that has specifically attempted to assess such factors from the outset. Instead, the norm has been to indirectly discover social and behavioral patterns primarily as a byproducts of epidemiological and clinical surveys. The exception to this has been a recent surge of research interest in this domain that was initiated by a commitment by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), although it is clear that more research is needed. The results of those few studies that have been conducted concerning the roles of behavioral (knowledge, attitudes, beliefs, practice) and socio-cultural factors are reviewed in this paper, highlighting how an acknowledgement of such factors contributes of a greater understanding of the relevant issues, thus allowing for more relevant and feasible health education/intervention programs. Finally, recent research conducted by two of the present authors in Nakhon Si Thammarat Province in Southern Thailand, which is noted for having the highest filariasis morbidity rate in the country, is presented and discussed. This is followed by recommendations for appropriate health education programs, and suggestions for future research.


The elasticity and failure of fluid-filled cellular solids: theory and experiment.
We extend and apply theories of filled foam elasticity and failure to recently available data on foods. The predictions of elastic modulus and failure mode dependence on internal pressure and on wall integrity are borne out by photographic evidence of distortion and failure under compressive loading and under the localized stress applied by a knife blade, and by mechanical data on vegetables differing only in their turgor pressure. We calculate the dry modulus of plate-like cellular solids and the cross over between dry-like and fully fluid-filled elastic response. The bulk elastic properties of limp and aging cellular solids are calculated for model systems and compared with our mechanical data, which also show two regimes of response. The mechanics of an aged, limp beam is calculated, thus offering a practical procedure for comparing experiment and theory. This investigation also thereby offers explanations of the connection between turgor pressure and crispness and limpness of cellular materials.


Adults who are mentally handicapped as consumers: issues and guidelines for interviewing.
This paper has arisen from an investigation of the lives and circumstances of 88 people who are mentally handicapped and living in their own homes or tenancies. This study is funded by the Economic and Social Research Council. The difficulties inherent in interviewing people who are mentally handicapped are outlined. This is followed by a consideration of the findings of previous research and a listing of guidelines for interviewing. The paper also explores consent procedures and issues pertaining to the measurement of satisfaction.


[Use of an immunoperoxidase method in situ for detecting recombinant clones of vaccinia virus containing an expressed gene of influenza viral hemagglutinins].
The vaccine L-IVP strain of vaccinia virus (VV) was used to construct the recombinant viral clones containing the influenza A hemagglutinin gene. The recombinant T plasmid was obtained with HA gene inserted in the vector pGS-20 (B. Moss) under the 7.5 K promoter of VV. A homologous recombination technique was used to insert the gene with the flanking TK sequences into vaccinia virus genome. The recombinant clones were selected by dot-hybridization with [32P]-labeled HA-probe. These recombinants were analysed for HA gene expression by the indirect immunoperoxidase method in situ using the peroxidase conjugate of the staphylococcal A-protein. This technique allows to obtain stable stained preparation and analyse the protein behavior at the ultrastructural level.


Decision Analysis Model Comparing Cost of Management Strategies for Pelvic Fracture Urethral Injuries.
We compare the costs associated with primary endoscopic realignment vs delayed elective bulbomembranous anastomotic urethroplasty after initial management of pelvic fracture urethral injuries with suprapubic tubes. Decision analysis was performed comparing the costs associated with suprapubic tube placement with a definitive bulbomembranous urethroplasty performed 2 to 3 months after injury to those associated with primary endoscopic realignment. Model assumptions based on literature review included success rates of 30% for primary endoscopic realignment, 92% for bulbomembranous urethroplasty and 50% for direct vision internal urethrotomy. Using an institutional patient database of patients undergoing suprapubic tube placement, bulbomembranous urethroplasty and direct vision internal urethrotomy, costs were estimated based on hospital and operating room costs and Medicare reimbursement rates. Sensitivity analyses were performed by varying model assumptions. Using data from the Nationwide Inpatient Sample and the National Trauma Data Bank®, the annual incidence of pelvic fracture urethral injuries nationwide was estimated. The total average cost of treating a pelvic fracture urethral injury with attempted primary endoscopic realignment is $11,043 vs $9,743 for suprapubic tube with elective bulbomembranous urethroplasty, for a savings of $1,300 (12%) per patient. For primary endoscopic realignment to be preferred, a success rate of 40% or better would be necessary. In addition, cost analysis calculation revealed that when bulbomembranous urethroplasty demonstrates an efficacy of 78% or greater, then suprapubic tube and elective bulbomembranous urethroplasty become more cost-effective than primary endoscopic realignment. Given the added costs and variable outcomes of primary endoscopic realignment and subsequent endoscopic interventions, the durability of definitive urethroplasty appears to be cost-effective in treating men with pelvic fracture urethral injuries.


Membrane glycoproteins involved in neurite fasciculation.
Lectin affinity chromatography combined with mAb production was used to identify chick neural cell surface molecules related to L1 antigen, a mouse neural glycoprotein implicated in cell-cell adhesion (Rathjen, F. G., and M. Schachner, 1984, EMBO (Eur. Mol. Biol. Organ.) J., 3:1-10). A glycoprotein, G4 antigen, isolated by mAb G4 from adult chick brain is described which comprises a major 135-kD component, a minor doublet at 190 kD, and diffusely migrating bands at 80 and 65 kD in SDS PAGE. This molecule is structurally related to mouse L1 antigen according to NH2-terminal amino acid sequence (50% identity) as well as the behavior of its components in two-dimensional IEF/SDS PAGE gels. A second chicken glycoprotein, F11 antigen, was isolated from adult chick brain using mAb F11. This protein has also a major 135-kD component and minor components at 170 kD and 120 kD. Both immunotransfer analysis with polyclonal antibodies to mAb G4 and to mAb F11 isolate and the behavior on IEF/SDS PAGE gels indicates that the major 135-kD component of F11 antigen is distinct from G4 antigen components. However, the 135-kD component of F11 antigen shares with G4 antigen and the neural cell adhesion molecule (NCAM) the HNK-1/L2 carbohydrate epitope. In immunofluorescence studies, G4 and F11 antigenic sites were found to be associated mainly with the surface of process-bearing cells, particularly in fiber-rich regions of embryonic brain. Although Fab fragments of polyclonal antibodies to mAbs G4 or F11 immunoaffinity isolate only weakly inhibit the Ca2+-independent aggregation of neural cells, they strongly inhibit fasciculation of retinal axons. Together these studies extend the evidence that bundling of axons reflects the combined effects of a group of distinct cell surface glycoproteins.


[Lipoxygenase and trypsin inhibitor inactivation in soymilk processing by direct milling and ultra high temperature (DM-UHT)].
Soymilk production by a new process based on Direct Milling of soy grits and Ultra High Temperature (DM-UHT) has been studied at laboratory scale in order to evaluate solids and protein extraction, lipoxygenases (LO) and Trypsin Inhibitors (TI) inactivation during milling and heat-treatment steps. For TI measurements in soy extracts and soymilk a modification of the classical Kakade method (17) was used. Highest extraction yields were accomplished at 70 degrees C and 2 minutes milling of soy grits. LO was appreciably inactivated when using, as dispersing medium for milling, 0.01M sodium carbonate (Residual Activity 14%) instead of water (Residual Activity 46%), so in this way lower levels of undesired substances can be generated. LO destruction in the resulting suspension was finished by a short heating (30 seconds) from 70 degrees C to boiling temperature (96 degrees C). On the other hand, TI were not fully inactivated in milling nor even in the steaming step at 96 degrees C for many minutes. The TI were inactivated to the accepted levels for soymilk in the final UHT step at 135 degrees C and 2 minutes, being possible at the same time to carry out the simultaneous microorganisms destruction.


[Visitation of orchid by Melipona capixaba Moure & Camargo (Hymenoptera: Apidae), bee threatened with extinction].
The stingless bee Melipona capixaba Moure & Camargo is a species restricted to the Atlantic forest in the Domingos Martins, Conceição do Castelo, Venda Nova do Imigrante and Afonso Cláudio County, in the Espírito Santo State, Brazil. Despite its cological importance as pollinator few studies have examined the ecology and biology of this bee. This note relates a case of the M. capixaba workers carrying pollinarium attached to the scuttellum. The pollinaria were identified as belonging to the orchid subtribe Maxillariinae species possibly of the genus Maxillaria sensu lato or Xylobium.


Metabolic acidosis and urinary acidification defect during the course of hemorrhagic fever with renal syndrome.
To evaluate urinary acidification defect and its contribution to metabolic acidosis (MA) during hemorrhagic fever with renal syndrome (HFRS), we serially analyzed acid-base balance and urinary acidification indices in 10 HFRS patients. Data of the patients were compared with those of 8 normal volunteers (NC). MA was observed in 6 of 8 patients in the oliguric phase, 5 of 7 in the early diuretic phase, 8 of 10 in the late diuretic phase and 2 of 9 in the convalescent phase. HFRS patients with MA had a higher plasma anion gap in the oliguric and early diuretic phases than NC and a higher plasma Cl/Na ratio in the late diuretic phase than NC. As compared with acid-loaded NC, HFRS patients had a higher urine pH in the oliguric, early diuretic and late diuretic phases, a higher urine anion gap (UAG) in the oliguric and early diuretic phases and a lower urinary NH4+ excretory rate in the oliguric, early diuretic and late diuretic phases. Overt distal acidification defect was observed in 6 of 8 patients in the oliguric phase, 3 of 7 in the early diuretic phase, 5 of 10 in the late diuretic phase and none of 9 in the convalescent phase. None of the convalescent patients had latent acidification defect. In conclusion, urinary acidification defect is marked in the oliguric and diuretic phases of severe HFRS and may play a role in the development of a high anion gap (AG) metabolic acidosis in the earlier phase and hyperchloremic MA in the later phase, but rapidly recovers in the convalescent phase.


CATER: Combined Animal Tracking & Environment Reconstruction.
Quantifying the behavior of small animals traversing long distances in complex environments is one of the most difficult tracking scenarios for computer vision. Tiny and low-contrast foreground objects have to be localized in cluttered and dynamic scenes as well as trajectories compensated for camera motion and drift in multiple lengthy recordings. We introduce CATER, a novel methodology combining an unsupervised probabilistic detection mechanism with a globally optimized environment reconstruction pipeline enabling precision behavioral quantification in natural environments. Implemented as an easy to use and highly parallelized tool, we show its application to recover fine-scale motion trajectories, registered to a high-resolution image mosaic reconstruction, of naturally foraging desert ants from unconstrained field recordings. By bridging the gap between laboratory and field experiments, we gain previously unknown insights into ant navigation with respect to motivational states, previous experience, and current environments and provide an appearance-agnostic method applicable to study the behavior of a wide range of terrestrial species under realistic conditions.


Regional differences in residential environments and the association of dwellings and residential factors with the sick house syndrome: a nationwide cross-sectional questionnaire study in Japan.
This study was conducted to clarify regional differences in residential factors and the association of those factors with dwellings having sick house syndrome (SHS) problems. The survey was conducted in six areas of northern and southern Japan. In terms of regional differences, dampness was not as severe in the dwellings in Sapporo as compared with that in areas in the south. SHS was defined using five categories of nasal, throat and respiratory, skin and general symptoms, which appeared frequently or not frequently and improved upon leaving the home. The dampness index was estimated by the sum of the presence of several indicators: condensation on the window panes and/or wall, visible mold growth, moldy odor, slow-drying wet towels in the bathroom, and water leakage. The dwellings where inhabitants showed any symptoms of SHS comprised 3.7% of all surveyed dwellings. We found significant associations between SHS and dampness index, odors, and stuffiness of the air. For dampness, the adjusted odds ratio (OR) increased with increased dampness index, adjusting for the age of the house, pets indoors, stuffiness of the air, and odors. These results showed an increased risk when several dampness indicators appeared simultaneously. To evaluate the associations of residential environments and Sick House Syndrome (SHS), this cross-sectional questionnaire study was conducted on 2297 dwellings in six areas in Japan from 2003 to 2004. The dwellings where inhabitants showed any of nasal, throat and respiratory, skin and general symptoms comprised 3.7% of all surveyed dwellings, and an increased risk for SHS was found when several dampness indicators, 'condensation', 'visible mold growth', 'moldy odor', 'slow drying wet towels in the bathroom' and 'water leakage', appeared simultaneously.


Renal nerve contribution to NaCl-exacerbated hypertension in spontaneously hypertensive rats.
Previous studies demonstrate that bilateral renal denervation enhances urinary sodium excretion and delays the onset of hypertension in young (7-week-old) spontaneously hypertensive rats (SHR) maintained on ordinary laboratory chow. We interpret these data as suggesting that increased renal nerve activity in this model contributes to hypertension by causing excess sodium retention. More recent studies show that dietary NaCl supplementation increases blood pressure and peripheral sympathetic nervous system activity in NaCl-sensitive SHR (SHR-S). The present study tests the hypothesis that the renal nerves contribute to the rise in arterial pressure caused by dietary NaCl supplementation in this model. SHR-S were fed a high (8%) or basal (1%) NaCl diet beginning at age 7 weeks. Bilateral renal denervation was carried out 2 weeks after the initiation of the diets, at which time systolic blood pressure was significantly higher in the high (compared with the basal) NaCl group. Systolic blood pressure was reduced slightly less in denervated SHR-S on the high (compared with basal) NaCl diet during the following 5 weeks. Renal denervation performed 1 week before initiation of the diets attenuated the subsequent development of hypertension equally in both groups. Both renal denervation and the high NaCl diet increased alpha 2-adrenergic receptor numbers in the kidney; renal denervation caused an approximately equal increase in alpha 2-adrenergic receptor binding in SHR-S on high and basal NaCl diets. The high NaCl diet increased plasma noradrenaline concentration, and renal denervation lowered mean arterial pressure but did not decrease circulating catecholamines in either diet group.(ABSTRACT TRUNCATED AT 250 WORDS)


Simulating the dynamics of complex plasmas.
Complex plasmas are low-temperature plasmas that contain micrometer-size particles in addition to the neutral gas particles and the ions and electrons that make up the plasma. The microparticles interact strongly and display a wealth of collective effects. Here we report on linked numerical simulations that reproduce many of the experimental results of complex plasmas. We model a capacitively coupled plasma with a fluid code written for the commercial package comsol. The output of this model is used to calculate forces on microparticles. The microparticles are modeled using the molecular dynamics package lammps, which we extended to include the forces from the plasma. Using this method, we are able to reproduce void formation, the separation of particles of different sizes into layers, lane formation, vortex formation, and other effects.


The distribution of refractive errors among children attending Lumbini Eye Institute, Nepal.
Uncorrected refractive error is an important cause of childhood blindness and visual impairment. To describe the patterns of refractive errors among children attending the outpatient clinic at the Department of Pediatric Ophthalmology, Lumbini Eye Institute, Bhairahawa, Nepal. Records of 133 children with refractive errors aged 5 - 15 years from both the urban and rural areas of Nepal and the adjacent territory of India attending the hospital between September and November 2010 were examined for patterns of refractive errors. The SPSS statistical software was used to perform data analysis. The commonest type of refractive error among the children was astigmatism (47 %) followed by myopia (34 %) and hyperopia (15 %). The refractive error was more prevalent among children of both the genders of age group 11-15 years as compared to their younger counterparts (RR = 1.22, 95 % CI = 0.66 - 2.25). The refractive error was more common (70 %) in the rural than the urban children (26 %). The rural females had a higher (38 %) prevalence of myopia than urban females (18 %). Among the children with refractive errors, only 57 % were using spectacles at the initial presentation. Astigmatism is the commonest type of refractive error among the children of age 5 - 15 years followed by hypermetropia and myopia. Refractive error remains uncorrected in a significant number of children.


Development of a Training Program for Law Enforcement K9 Handlers to Administer Naloxone.
As the opioid epidemic continues across the United States, law enforcement K9s (LEK9s) are at increased risk of accidental exposure and overdose. This study evaluated a novel training program teaching handlers to administer naloxone to their LEK9 in the event of an overdose. Seventy-five LEK9 handlers from a governmental agency attended a naloxone training session. A presurvey given to the handlers evaluated their knowledge of opioid overdose in LEK9s and their confidence administering naloxone. Officers were educated via a PowerPoint presentation about naloxone and how to administer it to their LEK9. A postsurvey evaluated changes in their knowledge and confidence as a result of the presentation. Sixty-two presurveys and 47 postsurveys were completed. Nearly all handlers had never given their LEK9 an intramuscular or intranasal injection. Most handlers were not comfortable monitoring their LEK9's vital signs for an opioid overdose. After the training, handlers demonstrated a mild increase in comfort level administering intramuscular and intranasal naloxone (15 and 14% increase, respectively). Comfort level monitoring vital signs and symptoms of an opioid overdose increased 38 and 32%, respectively. Handlers may not be fully prepared to assess and treat their LEK9 and may benefit from a targeted training program teaching them to administer naloxone.


Multiscale deformable registration for dual-energy x-ray imaging.
Dual-energy (DE) imaging of the chest improves the conspicuity of subtle lung nodules through the removal of overlying anatomical noise. Recent work has shown double-shot DE imaging (i.e., successive acquisition of low- and high-energy projections) to provide detective quantum efficiency, spectral separation (and therefore contrast), and radiation dose superior to single-shot DE imaging configurations (e.g., with a CR cassette). However, the temporal separation between high-energy (HE) and low-energy (LE) image acquisition can result in motion artifacts in the DE images, reducing image quality and diminishing diagnostic performance. This has motivated the development of a deformable registration technique that aligns the HE image onto the LE image before DE decomposition. The algorithm reported here operates in multiple passes at progressively smaller scales and increasing resolution. The first pass addresses large-scale motion by means of mutual information optimization, while successive passes (2-4) correct misregistration at finer scales by means of normalized cross correlation. Evaluation of registration performance in 129 patients imaged using an experimental DE imaging prototype demonstrated a statistically significant improvement in image alignment. Specific to the cardiac region, the registration algorithm was found to outperform a simple cardiac-gating system designed to trigger both HE and LE exposures during diastole. Modulation transfer function (MTF) analysis reveals additional advantages in DE image quality in terms of noise reduction and edge enhancement. This algorithm could offer an important tool in enhancing DE image quality and potentially improving diagnostic performance.


Meningococcal carriage in close contacts of cases.
Between 1 October 1986 and 31 March 1987, 55 cases of meningococcal disease were identified in the South-West of England, an attack rate of 1.54 per 100,000 during the study period. Antibiotics used in the treatment of the disease successfully eliminated nasopharyngeal carriage of meningococci in 13 out of 14 cases without use of rifampicin. The overall meningococcal carriage rate in 384 close contacts was 18.2% and the carriage rate of strains indistinguishable from the associated case strain was 11.1%. The carriage rate of indistinguishable strains in household contacts (16.0%) was higher than the carriage rate in contacts living at other addresses (7.0%, P less than 0.05). A 2-day course of rifampicin successfully eradicated meningococci from 46 (98%) of 47 colonized contacts. In one third of cases groupable meningococci were isolated from at least one household contact; 92% of these isolates were of the same serogroup as the associated case strain. When a meningococcus is not isolated from a deep site in a clinical case of meningococcal disease, culture of serogroup A or C strains from nasopharyngeal swabs of the case or of household contacts is an indication that the close contact group should be offered meningococcal A + C vaccine in addition to chemoprophylaxis. The failure in this and other studies to isolate meningococci from any household contact in the majority of cases may be due either to the relative insensitivity of nasopharyngeal swabbing in detecting meningococcal carriage or to the acquisition of meningococci by most index cases from sources outside the household.


Recall of diagnosis by men with ischaemic heart disease.
In a study of the prevalence of ischaemic heart disease in middle aged men in 24 British towns, the subjects were asked whether a doctor had ever told them that they had any form of cardiovascular disease. Their recall of various diagnoses was related to evidence of ischaemic heart disease obtained by an administered questionnaire on chest pain and electrocardiography. Twenty one per cent of men recalled a diagnosis of cardiovascular disease, in one quarter of whom it was ischaemic heart disease. There was a sixfold increase in the prevalence of recall of a diagnosis of ischaemic heart disease over the age range studied. Only one third of the men with possible myocardial infarction on questionnaire recalled such a diagnosis having been made by a doctor. Only half of those with a definite myocardial infarction on an electrocardiogram could recall a diagnosis of ischaemic heart disease. Even in severe (grade 2) angina 40% could not recall being told that they had heart disease. Overall, only one in five of those regarded as having ischaemic heart disease was able to recall such a diagnosis having been made by a doctor, and these were likely to be those most severely affected. Ischaemic heart disease is common in middle aged British men, but most of those affected are apparently not aware of their condition. This low level of awareness among patients and doctors may contribute to a lack of public concern regarding the need for action to reduce the incidence of ischaemic heart disease in Great Britain.


Food-Grade Physically Unclonable Functions.
Counterfeit products in the pharmaceutical and food industries have posed an overwhelmingly increasing threat to the health of individuals and societies. An effective approach to prevent counterfeiting is the attachment of security labels directly on drugs and food products. This approach requires the development of security labels composed of safely digestible materials. In this study, we present the fabrication of security labels entirely based on the use of food-grade materials. The key idea proposed in this study is the exploitation of food-grade corn starch (CS) as an encoding material based on the microscopic dimensions, particulate structure, and adsorbent characteristics. The strong adsorption of a food colorant, erythrosine B (ErB), onto CS results in fluorescent CS@ErB microparticles. Randomly positioned CS@ErB particles can be obtained simply by spin-coating from aqueous solutions of tuned concentrations followed by transfer to an edible gelatin film. The optical and fluorescence microscopy images of randomly positioned particles are then used to construct keys for a physically unclonable function (PUF)-based security label. The performance of PUFs evaluated by uniformity, uniqueness, and randomness analysis demonstrates the strong promise of this platform. The biocompatibility of the fabricated PUFs is confirmed with assays using murine fibroblast cells. The extremely low-cost and sustainable security primitives fabricated from off-the-shelf food materials offer new routes in the fight against counterfeiting.


Simultaneous integrated diffuse optical tomography and functional magnetic resonance imaging of the human brain.
A complete methodology has been developed to integrate simultaneous diffuse optical tomography (DOT) and functional magnetic resonance imaging (MRI) measurements. This includes development of an MRI-compatible optical probe and a method for accurate estimation of the positions of the source and detector optodes in the presence of subject-specific geometric deformations of the optical probe. Subject-specific head models are generated by segmentation of structural MR images. DOT image reconstruction involves solution of the forward problem of light transport in the head using Monte Carlo simulations, and inversion of the linearized problem for small perturbations of the absorption coefficient. Initial results show good co-localization between the DOT images of changes in oxy- and deoxyhemoglobin concentration and functional MRI data.


A phase II study of i.v. methylprednisolone in secondary-progressive multiple sclerosis.
To compare the tolerability and efficacy of two doses of i.v. methylprednisolone in patients with secondary-progressive MS. I.v. methylprednisolone administered in high or low dose every other month for up to 2 years to 108 patients with secondary-progressive MS. No significant difference in efficacy with the primary outcome, a comparison of the proportions of patients in each treatment group who experienced sustained progression of disability. A relative treatment effect was detected with the high-dose regimen as measured by the preplanned secondary analysis, a comparison of time to onset of sustained progression of disability. Drug-related adverse events were observed more frequently in high-dose recipients but serious drug-related adverse events were uncommon, and cessation of study drug was only required in one patient. The results of the secondary analysis of this study suggest that a phase III trial of corticosteroids for secondary-progressive MS is warranted.


[Acute ischemic spinal cord disease. Spinal cord infarction. A clinical study and MRI in 8 cases].
Acute spinal cord infarction (ASCI) occurs infrequently and may have diverse causes. The diagnosis of ASCI, and particularly of an anterior spinal artery syndrome (ASAS) can be confirmed nowadays by MRI, whereas in the past only necropsy confirmation was possible. Pathophysiology and long-term prognosis may be better known at present and treatments more consistent. We present the longitudinal study and clinical features of 8 patients suffering from ASCI. All of them were personally studied and had MRI examinations, often with sequential studies. three groups must be considered: one included 4 cases of ASAS at cervical level, the second 2 cases of ASAS at thoracic level and the third group with infarction of the conus medullaris (ICM), one of them developed during surgical repair of an infrarenal aortic aneurysm. Motor and sensory sequelae were assessed in each case together with possible etiological factors. In conclusion, recovery after ASAS tends to be dependent on the severity of the initial deficit. At cervical level, clinical and morphological findings argue in favour of an extrinsic selective compression of the C7 right radiculo-medullary artery as responsible for the ASA. At thoracic level, the artery preferentially occluded seems to be the sulco-commisural artery as a consequence of disc compression. Finally, an underlying peculiarity of the pattern of arterial supply is a probable predisposing factor for ICM. Generally, the long-term prognosis of ASCI is not necessarily bad.


Race, social class, and child abuse: Content and strength of medical professionals' stereotypes.
Black and poor children are overrepresented at every stage of the child welfare system, from suspicion of abuse to substantiation. Focusing on stereotypes as a source of bias that leads to these disparities, the current study examines the content and strength of stereotypes relating race and social class to child abuse as viewed by medical professionals. Doctors, nurses, and other medical professionals (Study 1: N = 53; Study 2: N = 40) were recruited in local hospitals and online through snowball sampling. Study 1 identified stereotype content by asking participants to list words associated with the stereotype that either (a) Black or (b) poor children are more likely to be abused by their parents, and responses were organized into construct groups. Study 2 determined stereotype strength by asking participants to rate how strongly the constructs generated in Study 1 related to either the race-abuse or social class-abuse stereotype. The content of stereotypes linking child abuse to Black or poor children are confounded, with approximately half the constructs shared by both stereotypes. Of the 10 shared constructs, only "Stressed" and "Neglect" differed in strength, with both significantly more strongly related to the social class-abuse than race-abuse stereotype, all ts(36-37) ≤ -2.23, ps ≤ .03, Cohen's ds ≥ .71. This research documents the existence, content, and strength of stereotypes that link race and social class to child abuse. These stereotypes have the potential to lead to medical misdiagnosis of abuse for Black and poor children.


Attitudes and Practices of a Sample of Nova Scotian Physicians for the Implementation of HIV Pre-Exposure Prophylaxis.
Pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool that requires the ongoing support of physicians to be accessible. Recently, Nova Scotia experienced a 100% increase in HIV diagnoses. The purpose of this study is to explore the relationship between physicians' support of PrEP, knowledge of PrEP, and PrEP prescribing history using the information-motivation-behavioral (IMB) skills model. An online survey was distributed to physicians in Nova Scotia, Canada, and eighty physicians participated. Two exploratory factor analyses were conducted with items from the Support of PrEP scale and Knowledge of PrEP scale. A mediation analysis was conducted to assess if knowledge of PrEP mediated the relationship between support of PrEP and whether physicians have prescribed PrEP in the past. On average, physicians reported strong support for PrEP, and as support for PrEP increased so did knowledge of PrEP. Further, physicians who had prescribed PrEP demonstrated strong knowledge of PrEP and physicians who had not prescribed PrEP reported feeling neutral. The 95% bootstrap confidence interval indirect effect of Support for PrEP on prescription history did not include zero (B = 1.59, 95% BsCI [0.83, 3.57]) demonstrating that the effect of support for PrEP is mediated by knowledge of PrEP. The most commonly identified barrier to prescribing PrEP was the lack of drug coverage among patients. The results of the mediation analysis support the IMB skills model regarding support for PrEP, Knowledge of PrEP, and having prescribed PrEP in the past. Our findings suggest that to improve PrEP uptake in Nova Scotia, educational interventions for physicians and universal coverage of the drug would be necessary.


Comparison of the effects of pilocarpine and cevimeline on salivary flow.
The aim of the present study was to compare the effect of low-dose pilocarpine and cevimeline as stimulants for salivary flow in healthy subjects. In this cross-over clinical trial with a 1-week washout period, 40 male volunteers were submitted to an oral dose of pilocarpine 1% (Salagen) -60 microg kg(-1) body-weight (Group 1) or Cevimeline (Evoxac) -30 mg (Group 2). Saliva samples were collected and the salivary flow rate was measured (ml min(-1)) at baseline and 20, 40, 60, 80, 140 and 200 min after administration of drugs. In addition, salivary secretion was also measured under mechanical stimulation to observe salivary gland function. The data were analyzed by Friedman and Wilcoxon signed-rank tests (significance level = 5%). Pilocarpine and cevimeline significantly increased salivary flow 140 min after intake. There was a significant higher secretion with cevimeline 140 and 200 min after administration. There were no differences seen among subjects in the salivary glands function by mechanical stimulation. Both drugs showed efficacy in increasing the salivary flow in healthy volunteers, but cevimeline was more effective than pilocarpine.


Inhibiting NF-κB in the developing lung disrupts angiogenesis and alveolarization.
Bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy, is characterized by arrested alveolar development. Pulmonary angiogenesis, mediated by the vascular endothelial growth factor (VEGF) pathway, is essential for alveolarization. However, the transcriptional regulators mediating pulmonary angiogenesis remain unknown. We previously demonstrated that NF-κB, a transcription factor traditionally associated with inflammation, plays a unique protective role in the neonatal lung. Therefore, we hypothesized that constitutive NF-κB activity is essential for postnatal lung development. Blocking NF-κB activity in 6-day-old neonatal mice induced the alveolar simplification similar to that observed in BPD and significantly reduced pulmonary capillary density. Studies to determine the mechanism responsible for this effect identified greater constitutive NF-κB in neonatal lung and in primary pulmonary endothelial cells (PEC) compared with adult. Moreover, inhibiting constitutive NF-κB activity in the neonatal PEC with either pharmacological inhibitors or RNA interference blocked PEC survival, decreased proliferation, and impaired in vitro angiogenesis. Finally, by chromatin immunoprecipitation, NF-κB was found to be a direct regulator of the angiogenic mediator, VEGF-receptor-2, in the neonatal pulmonary vasculature. Taken together, our data identify an entirely novel role for NF-κB in promoting physiological angiogenesis and alveolarization in the developing lung. Our data suggest that disruption of NF-κB signaling may contribute to the pathogenesis of BPD and that enhancement of NF-κB may represent a viable therapeutic strategy to promote lung growth and regeneration in pulmonary diseases marked by impaired angiogenesis.


A panel of irradiation-reduced hybrids selectively retaining human chromosome 11p13: their structure and use to purify the WAGR gene complex.
The irradiation-fusion technique offers a means to isolate intact subchromosomal fragments of one mammalian species in the genetic background of another. Irradiation-reduced somatic cell hybrids can be used to construct detailed genetic and physical maps of individual chromosome bands and to systematically clone genes responsible for hereditary diseases on the basis of their chromosomal position. To assess this strategy, we constructed a panel of hybrids that selectively retain the portion of human chromosome band 11p13 that includes genes responsible for Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (constituting the WAGR syndrome). A hamster-human hybrid containing the short arm of chromosome 11 as its only human DNA (J1-11) was gamma-irradiated and fused to a Chinese hamster cell line (CHO-K1). We selected secondary hybrid clones that express MIC1 but not MER2, cell-surface antigens encoded by bands 11p13 and 11p15, respectively. These clones were characterized cytogenetically by in situ hybridization with human repetitive DNA and were tested for their retention of 56 DNA, isozyme, and antigen markers whose order on chromosome 11p is known. These cell lines appear to carry single, coherent segments of 11p spanning MIC1, which range in size from 3000 kb to more than 50,000 kb and which are generally stable in the absence of selection. In addition to the selected region of 11p13, two cell lines carry extra fragments of the human centromere and two harbor small, unstable segments of 11p15. As a first step to determine the size and molecular organization of the WAGR gene complex, we analyzed a subset of reduced hybrids by pulsed-field gel electrophoresis. A small group of NotI restriction fragments comprising the WAGR complex was detected in Southern blots with a cloned Alu repetitive probe. One of the cell lines (GH3A) was found to carry a stable approximately 3000-kb segment of 11p13 as its only human DNA. The segment encompasses MIC1, a recurrent translocation breakpoint in acute T-cell leukemia (TCL2), and most or all of the WAGR gene complex, but does not include the close flanking markers D11S16 and delta J. This hybrid forms an ideal source of molecular clones for the developmentally fascinating genes underlying the WAGR syndrome.


Targeting PDGFR-β in Cholangiocarcinoma.
Cholangiocarcinomas (CCAs) are highly desmoplastic neoplasms with a tumour microenvironment plentiful in myofibroblasts (MFBs). MFB-derived PDGF-BB survival signalling is a mediator of CCA cell resistance to apoptotic stimuli. This raises the concept that targeting PDGFR-β, a cognate receptor of PDGF-BB, represents a potential strategy for the treatment of human CCA. Herein, we examine a role for inhibiting PDGFR-β in restoring CCA cell sensitivity to apoptotic stimuli in vitro and in vivo. We employed human CCA samples from 41 patients (19 intrahepatic and 22 extrahepatic CCA samples), the human CCA cell lines KMCH-1 and HUCCT-1 as well as shPDGFR-β-KMCH-1 and human myofibroblastic LX-2 cells for these studies. In vivo-experiments were conducted using a syngeneic rat orthotopic CCA model. Of several MFB-derived growth factors profiled, PDGF-BB and CTGF were most abundantly expressed; however, only PDGF-BB attenuated tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity. Co-culturing CCA cells with PDGF-BB-secreting MFBs significantly decreased TRAIL-induced CCA cell apoptosis when compared with monoculture conditions; this cytoprotective effect was abrogated in the presence of the tyrosine kinase inhibitors imatinib mesylate or linifanib, which inhibit PDGFR-β. Consistent with these findings, MFB-imparted cytoprotection also was abolished when PDGFR-β was knocked down as demonstrated in shPDGFR-β-KMCH-1 cells. Finally, administration of imatinib mesylate increased CCA cell apoptosis and reduced tumour growth in a rodent in vivo-CCA model that mimics the human disease. Targeting PDGFR-β sensitizes CCA cells to apoptotic stimuli and appears to be therapeutic in vivo.


Evaluation of ACE-inhibitor Induced Laryngeal Edema Using Fiberoptic Scope: A Case Report.
This is a case report of a 55-year-old woman with a past medical history of hypertension who presented to the emergency department with upper lip and cheek swelling isolated to the right side of her face. She was on lisinopril for several years and had never had an episode of swelling in the past. Her vital signs were stable. However, on reassessment, the patient's right sided swelling progressed to the entire upper lip and she complained of swelling in her submandibular space. Although no swelling was appreciated to the submandibular space on physical exam, and the patient still did not have any signs or symptoms of respiratory distress, the decision was made to use a fiberoptic laryngoscope to evaluate her airway. Fiberoptic laryngoscope showed noticeable laryngeal edema which did not improve after treatment, and the patient was admitted to the medical intensive care unit for close airway observation. This case highlights the use of fiberoptic laryngoscope by emergency physicians in the evaluation of patients with relatively benign appearing angioedema. ACE-I, angioedema, fiberoptic laryngoscope, laryngeal edema, tranexamic acid.


Quality of life and leisure participation in children with neurodevelopmental disabilities: a thematic analysis of the literature.
The aim of this systematic review was to document evidence of the association between leisure participation and quality of life (QoL) in children with neurodevelopmental disabilities, and to identify the main factors that further clarify this relationship. An electronic search of the literature was conducted using Medline, Embase, PsycInfo, CINAHL, ERIC, OT Seeker, and the Cochrane library using relevant MESH heading and key words. An inductive thematic analysis was used to synthesize main findings from the studies. The mixed methods appraisal tool (MMAT) was used to assess the methodological quality of the included studies. Nineteen studies were included in this systematic review. All 19 studies fulfilled most of the criteria outlined by the MMAT for each study design (quantitative, qualitative, and mixed methods). Mixed methods studies had the lowest MMAT scores. Seven themes were identified that further elucidate the important relationships between leisure participation and QoL: active physical leisure participation and physical well-being; leisure participation and self; leisure participation and emotional well-being; leisure participation and social well-being; leisure participation and cognition; leisure preferences and well-being; and negative aspects of leisure participation. The use of thematic analysis enabled the synthesis of findings from quantitative, qualitative, and mixed methods study designs. Participating in both naturally occurring, spontaneous forms of leisure activities and participating in more structured types of leisure and therapeutic programs that focus on leisure contribute to improving the QoL of children with neurodevelopmental disabilities. A key aspect to consider is the child's ability to participate in his/her preferred leisure activities. Environmental adaptations may be required to ensure that the leisure opportunities meet the children's capabilities and contribute positively to their QoL.


Bioactive Metabolites from Marine Algae as Potent Pharmacophores against Oxidative Stress-Associated Human Diseases: A Comprehensive Review.
In addition to cancer and diabetes, inflammatory and ROS-related diseases represent one of the major health problems worldwide. Currently, several synthetic drugs are used to reduce oxidative stress; nevertheless, these approaches often have side effects. Therefore, to overcome these issues, the search for alternative therapies has gained importance in recent times. Natural bioactive compounds have represented, and they still do, an important source of drugs with high therapeutic efficacy. In the ''synthetic'' era, terrestrial and aquatic photosynthetic organisms have been shown to be an essential source of natural compounds, some of which might play a leading role in pharmaceutical drug development. Marine organisms constitute nearly half of the worldwide biodiversity. In the marine environment, algae, seaweeds, and seagrasses are the first reported sources of marine natural products for discovering novel pharmacophores. The algal bioactive compounds are a potential source of novel antioxidant and anticancer (through modulation of the cell cycle, metastasis, and apoptosis) compounds. Secondary metabolites in marine Algae, such as phenolic acids, flavonoids, and tannins, could have great therapeutic implications against several diseases. In this context, this review focuses on the diversity of functional compounds extracted from algae and their potential beneficial effects in fighting cancer, diabetes, and inflammatory diseases.


Study of the analgesic, anti-inflammatory, and gastric effects of gabapentin.
Gabapentin, a drug used to treat neuropathic pain, was evaluated in models of acute nociceptive pain, in instances of haloperidol-induced catalepsy, carrageenan-induced paw edema, gastric lesions caused by indomethacin or ethanol, and gastric acid secretion in rats. Reaction time in a hot plate assay was delayed by gabapentin. The antinociceptive effect of the drug was produced with a dose of 12.5 mg/kg and a maximal increase in hot plate latency of 68% 1 h after drug administration was produced at 100 mg/kg. Gabapentin (25, 50 or 100 mg/kg) caused a significant rise in current threshold in a tail electrical stimulation test in mice, resulting in values of 20, 30, and 60.5% vs. control values, 1 h post-dosing. With the agent, the duration of paw licking following intraplantar capsaicin injection decreased in a dose-dependent manner. In contrast, gabapentin failed to have antinociceptive action in a mouse acetic-acidinduced writhing assay. The drug (12.5-50 mg/kg) increased the duration of catalepsy induced by haloperidol by 33.5, 47.4, and 53.2%, respectively. It had an anti-inflammatory effect at doses of 25 or 50 mg/kg. Gabapentin (12.5-50 mg/kg) reduced the number and severity of gastric mucosal lesions induced by subcutaneous indomethacin (20 mg/kg) or intragastric 96% ethanol, but at doses of 50 and 100 mg/kg it increased gastric acid secretion. In conclusion, gabapentin decreased thermal, electrical, and chemogenic pain but not visceral pain and had a gastric protective effect.


Digital simulation of two-dimensional random fields with arbitrary power spectra and non-Gaussian probability distribution functions.
Methods for simulation of two-dimensional signals with arbitrary power spectral densities and signal amplitude probability density functions are disclosed. The method relies on initially transforming a white noise sample set of random Gaussian distributed numbers into a corresponding set with the desired spectral distribution, after which this colored Gaussian probability distribution is transformed via an inverse transform into the desired probability distribution. In most cases the method provides satisfactory results and can thus be considered an engineering approach. Several illustrative examples with relevance for optics are given.


Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue.
Cardiac tissue engineering has made notable progress in recent years with the advent of an experimental model based on neonatal cardiomyocytes entrapped in collage gels and purified basement membrane extract, known as "engineered heart tissues" (EHTs). EHTs are a formidable display of tissue-level contractile function and cellular-level differentiation, although they suffer greatly from mass transport limitations due to the high density of metabolically active cells and the diffusion-limited nature of the hydrogel. In this report, a mathematical model was developed to predict oxygen levels inside a one-dimensional, diffusion-limited model of EHT. These predictions were then compared to values measured in corresponding experiments with a hypoxia-sensitive stain (pimonidazole). EHTs were cast between two plastic discs, which allowed for mass transfer with the culture medium to occur in only the radial direction. EHTs were cultured for up to 36 h in the presence of pimonidazole, after which time they were snap-frozen, histologically sectioned, and stained for bound pimonidazole. Quantitative image analysis was performed to measure the distance from the culture medium at which hypoxia first occurs under various conditions. As tested by variation of simple design parameters, the trends in oxygen profiles predicted by the model are in reasonable agreement with those obtained experimentally, although a number of ambiguities related to the specific model parameters led to a general overprediction of oxygen concentrations. Based on the sensitivity analysis in the present study, it is concluded that diffusion-reaction models may offer relatively precise predictions of oxygen concentrations in diffusion-limited tissue constructs.


Haematolohical profile of subacute oral toxicity of molybdenum and ameliorative efficacy of copper salt in goats.
Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline in the mean values of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean corpuscular hemoglobin concentration (MCHC), with a significant increase in neutrophil level and mean corpuscular volume (MCV). However, values of erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential leukocyte count were not significantly altered. On comparing observations of ameliorative group with the group 1 goats, it is concluded that the ameliorative copper salt has beneficial effects in alleviating the alterations in the values of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils.


Dynamics of cooperativity in chemical sensing among cell-surface receptors.
Cooperative interactions among sensory receptors provide a general mechanism to increase the sensitivity of signal transduction. In particular, bacterial chemotaxis receptors interact cooperatively to produce an ultrasensitive response to chemoeffector concentrations. However, cooperativity between receptors in large macromolecular complexes is necessarily based on local interactions and consequently is fundamentally connected to slowing of receptor-conformational dynamics, which increases intrinsic noise. Therefore, it is not clear whether or under what conditions cooperativity actually increases the precision of the concentration measurement. We explicitly calculate the signal-to-noise ratio (SNR) for sensing a concentration change using a simple, Ising-type model of receptor-receptor interactions, generalized via scaling arguments, and find that the optimal SNR is always achieved by independent receptors.


Association between Cyclic Meditation and Creative Cognition: Optimizing Connectivity between the Frontal and Parietal Lobes.
Important stages of creativity include preparation, incubation, illumination, and verification. Earlier studies have reported that some techniques of meditation promote creativity but have not specified which stage is enhanced. Here, we report the influence of cyclic meditation (CM) on creative cognition measured by a divergent thinking task. Our aim was to determine the degree of association between the two. Twenty-four university students were randomly assigned to an experimental group (CM) and controls (Supine Rest), 35 min/day for 7 days. Creativity performance was assessed pre and post using Abbreviated Torrance Test for Adults (ATTA), while 64-channel electroencephalography (EEG) was used to measure brain activity during both CM/SH and the creativity test. Results indicated that CM training improved creativity performance, producing a shift to predominant gamma activity during creativity compared controls who showed delta activity. Furthermore, the experimental group showed more activation of frontal and parietal regions (EEG leads F3, F4 and P3, P4) than controls, i.e., the regions of the executive network responsible for creative cognition, our particular regions of interest where specialized knowledge is being stored. Improvement on creativity test performance indicates that CM increases association and strengthens the connectivity between frontal and parietal lobes, the major nodes of default mode network and executive attention network, enhancing the important stages of creativity such as preparation, incubation, and illumination.


Psilocybin: reaction with a fraction of rat brain.
Psilocybin, a hallucinogen, formed a blue color with a subfraction of rat-brain mitochondria believed to contain nerve-ending particles. Color formation increased with pH, did not require oxygen, and involved a component that could not be solubilized. The effect was not shown by chemically related neuroactive compounds, such as bufotenine and serotonin, and was antagonized by only tyramine or ethylenediaminetetraacetic acid.


Norrin: molecular and functional properties of an angiogenic and neuroprotective growth factor.
Norrin is a secreted signaling molecule with structural and functional characteristics of an autocrine and/or paracrine acting growth factor. In the eye, Norrin is constitutively expressed in Müller cells. Norrin specifically binds to Frizzled-4 receptors and activates the canonical Wnt/β-catenin signaling pathway that is profoundly enhanced when Tspan12 is present at the Norrin/Frizzled-4 receptor complex. In the absence of Norrin or Frizzled-4, intraretinal capillaries are not formed during developmental angiogenesis. As a result there is considerable evidence that Norrin and Frizzled-4 are part of an essential signaling system that controls the formation of the retinal vasculature during eye development. Intriguingly, Norrin promotes vessel regrowth and induces the formation of intraretinal capillaries following oxygen-induced retinopathy in mice, an animal model of retinopathy of prematurity. Moreover, Norrin has pronounced neuroprotective properties on retinal ganglion cells (RGC) with the distinct potential to decrease the damaging effects of excitotoxic NMDA-induced RGC injury. The neuroprotective effects of Norrin similarly involve an activation of Wnt/β-catenin signaling and the subsequent induction of neuroprotective growth factor synthesis in Müller cells, such as that of fibroblast growth factor-2 (FGF2) or ciliary neurotrophic factor (CNTF). Overall, Norrin and the molecules involved in its signaling pathway appear to be promising targets to develop strategies that induce intraretinal vessel formation in patients suffering from ischemic retinopathies, or that increase RGC survival in glaucoma.