Phytochrome regulates gibberellin biosynthesis during germination of photoblastic lettuce seeds.
Germination of lettuce (Lactuca sativa L.) seed is regulated by phytochrome. The requirement for red light is circumvented by the application of gibberellin (GA). We have previously shown that the endogenous content of GA1, the main bioactive GA in lettuce seeds, increases after red-light treatment. To clarify which step of GA1 synthesis is regulated by phytochrome, cDNAs encoding GA 20-oxidases (Ls20ox1 and Ls20ox2, for L. sativa GA 20-oxidase) and 3beta-hydroxylases (Ls3h1 and Ls3h2 for L. sativa GA 3beta-hydroxylase) were isolated from lettuce seeds by reverse-transcription polymerase chain reaction. Functional analysis of recombinant proteins expressed in Escherichia coli confirmed that the Ls20ox and Ls3h encode GA 20-oxidases and 3beta-hydroxylases, respectively. Northern-blot analysis showed that Ls3h1 expression was dramatically induced by red-light treatment within 2 h, and that this effect was canceled by a subsequent far-red-light treatment. Ls3h2 mRNA was not detected in seeds that had been allowed to imbibe under any light conditions. Expression of the two Ls20ox genes was induced by initial imbibition alone in the dark. The level of Ls20ox2 mRNA decreased after the red-light treatment, whereas that of Ls20ox1 was unaffected by light. These results suggest that red light promotes GA1 synthesis in lettuce seeds by inducing Ls3h1 expression via phytochrome action.


Pathogenic Impact of Fatty Acid-Binding Proteins in Parkinson's Disease-Potential Biomarkers and Therapeutic Targets.
Parkinson's disease is a neurodegenerative condition characterized by motor dysfunction resulting from the degeneration of dopamine-producing neurons in the midbrain. This dopamine deficiency gives rise to a spectrum of movement-related symptoms, including tremors, rigidity, and bradykinesia. While the precise etiology of Parkinson's disease remains elusive, genetic mutations, protein aggregation, inflammatory processes, and oxidative stress are believed to contribute to its development. In this context, fatty acid-binding proteins (FABPs) in the central nervous system, FABP3, FABP5, and FABP7, impact α-synuclein aggregation, neurotoxicity, and neuroinflammation. These FABPs accumulate in mitochondria during neurodegeneration, disrupting their membrane potential and homeostasis. In particular, FABP3, abundant in nigrostriatal dopaminergic neurons, is responsible for α-synuclein propagation into neurons and intracellular accumulation, affecting the loss of mesencephalic tyrosine hydroxylase protein, a rate-limiting enzyme of dopamine biosynthesis. This review summarizes the characteristics of FABP family proteins and delves into the pathogenic significance of FABPs in the pathogenesis of Parkinson's disease. Furthermore, it examines potential novel therapeutic targets and early diagnostic biomarkers for Parkinson's disease and related neurodegenerative disorders.


HCV infection: pathogenesis, clinical manifestations and therapy.
Chronic hepatitis C virus (HCV) infection is a worldwide public health problem with a global prevalence of 2-3%. It is believed that about 170 million people are currently infected (about 3% of the world's population), and a further 3-4 million are infected each year. HCV is the main reason for liver transplantation in the developed world, and the main cause of liver-related morbidity and mortality in a number of countries, including Italy. It is not only a frequent cause of chronic liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma, but is also involved in the pathogenesis of various autoimmune and rheumatic disorders (arthritis, vasculitis, sicca syndrome, porphyria cutanea tarda, lichen planus, nephropathies, thyroid diseases, and lung fibrosis), as well as in the development of B-cell lymphoproliferative diseases. Furthermore, patients suffering from C hepatitis tend to produce rheumatoid factor, cryoglobulins and a large series of autoantibodies (ANA, anti-SSA/SSB, SAM, ATG, aCL). The use of glucocorticoids or immuno-suppressant agents in HCV infected individuals, which are needed to treat autoimmune and rheumatic disorders, leads to a risk of worsening the clinical outcome of HCV. Under these conditions, the viral infection often needs to be treated with antiviral agents, mainly pegylated interferon combined with ribavirin. However, cyclosporine A seems to be safe and effective in patients with autoimmune disease (AD) and concomitant chronic HCV infection as is documented by the reduction in viremia and transaminases, particularly in patients with high baseline levels. Finally, HCV is the main trigger of mixed cryoglobulinemia. An attempt at viral eradication is therefore indicated in most patients, and is particularly effective in the case of mild or moderate manifestations. In severe cases, rituximab is an apparently safe and effective alternative to conventional immunosuppression and, specifically, it controls B-cell proliferation.


Morphological study of resin-dentin bonding with TEM and in-lens FESEM.
To evaluate the morphological characteristics of the dentin-resin interface using high-magnification electron microscopy and correlate the TEM findings of resin-dentin interfaces with the corresponding in-lens Field Emission SEM (FEISEM) observation. Twelve 800 microm-thick dentin disks were obtained from middle dentin and assigned to four groups: (1) a self-etching adhesive material, Clearfil SE Bond; (2) a solvent-free total-etch simplified adhesive, One Coat Bond; (3) an acetone-based total-etch simplified adhesive, Prime&Bond NT; (4) an acetone-based total-etch simplified adhesive, Prime&Bond NT, upon a short dentin deproteinization with 10% NaOCl gel (AD Gel) for 15 seconds. Disks were restored with a 1 mm thick layer of a low-viscosity composite. Four sticks with a cross section of 1 mm2 were taken from each restored dentin disk, decalcified in buffered 10% EDTA, fixed, and stained with lead citrate followed by uranyl acetate, or kept in water. The sticks were sectioned in 85 nm-thick slices, and mounted on Ni grids. After TEM observation, the same grids were coated with a 1.5 nm Pt-C film and observed under the FEISEM. The TEM analysis revealed an intimate adaptation of all adhesive systems to dentin, with penetrating resin tags observed in transverse sections. The FEISEM revealed novel morphological features usually observed in the resin-dentin interface with distinctive arrangement for each of the adhesive systems. FEISEM and TEM appear as mutually complementary tools for the fine observation of the ultra-structure and the spatial relationship between the resin components and the collagen fibers of the hybrid layer.


Changes in chronotype after stroke: a pilot study.
This study aimed to elucidate associations between stroke onset and severity as well as chronotype (phase of entrainment) and internal time of stroke. Fifty-six first-ever ischemic stroke patients participated in a cross-sectional study assessing chronotype (mid-sleep on work-free days corrected for sleep deficit on workdays; MSFsc) by applying the Munich ChronoType Questionnaire (MCTQ). The MCTQ was completed twice, on average 68 ± 24 (SD) days post stroke and retrospectively for the time before stroke. To assess the impact of stroke in relation to internal time, InTstroke was calculated as MSFsc minus local time of stroke. Stroke severity was assessed via the standard clinical National Institute Health Stroke Scale (NIHSS) and modified Ranking Scale (mRS), both at hospital admission and discharge. Overall, most strokes occurred between noon and midnight. There was no significant association between MSFsc and stroke onset. MSFsc changed significantly after stroke, especially in patients with more severe strokes. Changes in MSFsc varied with InTstroke - the earlier the internal time of a stroke relative to MSFsc-before-stroke, the more MSFsc advanced after stroke. In addition, we provide first evidence that MSFsc changes varied between stroke locations. Larger trials are needed to confirm these findings.


Submeatal injection of polytetrafluoroethylene paste for the endoscopic treatment of vesicoureteric reflux in adults.
The injection of submeatal Teflon paste is often used for the treatment of paediatric vesicoureteric reflux (VUR). We present our results using this treatment in 7 adults and 1 female child; 11 ureters were injected with a 73% success rate. The simplicity of the procedure and the encouraging results make this a desirable treatment for adult VUR.


Acyclovir Unresponsive Herpes Simplex Encephalitis in a child successfully treated with the addition of Foscarnet: Case report.
Herpes simplex encephalitis (HSE) is the most common cause of sporadic focal encephalitis worldwide. Acyclovir is the treatment of choice of HSE since the 1980s. After the widespread use of acyclovir, HSE related mortality rate had reduced but resistant strains emerged. Acyclovir resistant HSV incidence was reported as about 0.5 % and 3.5 %-10 % in immunocompetent and immunocompromised patients, respectively. Herein, a 12-year-old immunocompetent patient with HSV-1 encephalitis who was successfully treated with combined acyclovir and foscarnet therapy is described. In the case of deteriorating clinical condition under acyclovir treatment even if the absence of demonstration of increased CSF HSV viral load, the possibility of acyclovir resistant HSE and the addition of foscarnet to the acyclovir treatment might be considered.


Human Umbilical Cord Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Reduce Skin Inflammation In Vitro.
The protective roles of extracellular vesicles derived from human umbilical cord mesenchymal stem cells against oxazolone-induced damage in the immortalized human keratinocyte cell line HaCaT were investigated. The cells were pretreated with or without UCMSC-derived extracellular vesicles 24 h before oxazolone exposure. The pretreated UVMSC-EVs showed protective activity, elevating cell viability, reducing intracellular ROS, and reducing the changes in the mitochondrial membrane potential compared to the cells with a direct oxazolone treatment alone. The UCMSC-EVs exhibited anti-inflammatory activity via reducing the inflammatory cytokines IL-1β and TNF-α. A mechanism study showed that the UCMSC-EVs increased the protein expression levels of SIRT1 and P53 and reduced P65 protein expression. It was concluded that UVMSC-EVs can induce the antioxidant defense systems of HaCaT cells and that they may have potential as functional ingredients in anti-aging cosmetics for skin care.


Childhood chronic-kidney-disease: a longitudinal-qualitative study of families learning to share management early in the trajectory.
To explore the ways families learn to share management during the early stages of childhood chronic-kidney-disease. This longitudinal, descriptive study based on the tenets of grounded theory, aimed to derive meaning about family-professional interactions during shared management. Data were obtained from six newly referred families, four renal nurses, four paediatric nephrologists and one dietician through: 36 semi-structured interviews, 21 case-note reviews and four child/parent learning diaries. Three learning stages were identified: dependent (families' understanding was superficial, they lacked underlying knowledge and were totally reliant on professional guidance); co-dependent (families engaged competently in management but still required extensive guidance); independent (families communicated effectively with staff and competently adjusted management within professionally defined parameters). Five families actively shared management from early in the trajectory and progressed to independent learning when, by mutual agreement, professional input to management gradually decreased. The remaining family adopted a passive approach to management, did not progress to independent learning and remained reliant on professional input. Families in this study demonstrated three learning stages in becoming competent at management. Future research is needed to investigate the ways professionals promote family competence early in the trajectory and the factors that can facilitate or hinder families' progression to independent learning.


Clinicodemographic characteristics and prognostic role of myasthenia gravis in thymoma: Experience from a Saudi population.
The objectives of the study were to determine the clinicodemographic characteristics and the prognostic role of myasthenia gravis (MG) in thymoma. The records of patients who underwent surgical resection of thymoma at King Faisal Specialist Hospital and Research Center in the past 23 years were reviewed. Seventy thymoma patients were finally included and were then categorized based on MG status into the MG group (39 patients) and the non-MG group (31 patients). Collected data included patients' demographic characteristics, tumor characteristics, and postoperative clinical outcomes. All analyses were conducted using SPSS. The comparison between both groups was tested using the Student t-test and Chi-square test for continuous and categorical variables, respectively. A P = 0.05 or less indicated statistical significance. Patients' age ranged from 11 to 76 years, and female predominance was observed (55.7%). Compared to the non-MG group, no difference in patients' gender was observed (P = 0.058); however, MG patients had a younger age (39.30 vs. 48.77, P = 0.0095). No difference was noted between both groups based on the World Health Organization classification (P = 0.398), but MG patients tended to present with less-advanced tumors based on the TNM classification (P = 0.039) and lower stage based on the MASAOKA staging system (P = 0.017). No significant change in tumor size (P = 0.077), resectability (P = 0.507), and adjuvant therapy (P = 0.075) were observed. MG was not significantly associated with postoperative complications, morbidity, or mortality. However, it exhibited a prognostic protective role in terms of lower recurrence (2.56% vs. 35.48%, P = 0.0001) and longer survival duration (18.62 vs. 10.21 years, P < 0.001) as compared to non-MG patients. MG occurrence in thymoma patients is more likely to occur at a younger age, higher TNM classification, and advanced MASAOKA stage. Although no significant association was noted between MG and complications and mortality, MG exhibited a protective role in thymoma by providing a lower recurrence rate and longer survival duration.


Association of long lasting unsurmountable histamine H2 blockade and gastric carcinoid tumours in the rat.
The oral administration of loxtidine, a potent histamine H2-antagonist, to a total of 378 rats at doses of 50, 185, or 685 mg/kg/day for 116 weeks resulted in the late formation of carcinoid tumours of the gastric fundus. The first such tumour was detected after 712 days of treatment. There was no dose related response; 11 rats at the low level of treatment were affected, 12 at the intermediate and 11 at the high. Twenty seven females but only seven males were affected. No gastric tumours were found in the 228 controls. There is no evidence that loxtidine acts as a direct carcinogen and it is suggested that the tumours were the result of prolonged achlorhydria produced by a potent unsurmountable histamine H2 receptor antagonist.


Serological biomarkers of hepatocellular carcinoma in Egyptian patients.
Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. In Egypt, the disease is usually detected in an advanced stage at which no treatment may be effective including surgery. Early detection of the disease is thus an important goal allowing the patient to be treated before the enlargement of the tumor or its metastasis to distant organs. Tumor markers are serological agents which serum level may be useful in predicting the presence of the tumor at early stages. Alpha fetoprotein (AFP) which is the golden marker for HCC is of low sensitivity, therefore, additional markers such as alpha-L-fucosidase (AFU), transforming growth factors alpha and beta (TGF-α and TGF-β) and interleukin-8 (IL-8) are suggested to be simultaneously evaluated in order to enhance the detection of HCC. A total of 96 patients with different liver diseases such as HCC, hepatitis C virus (HCV), hepatitis B virus (HBV) and cirrhotic patients are included in this study. Sixteen healthy volunteers are used as a control group. In patients with HCC each of AFP, AFU, TGF-α and TGF-β recorded significantly higher levels than the other patient groups and controls. HCC patients recorded significantly lower level of IL-8 compared to the other patient groups but significantly higher than the control. For AFP, AFU, TGF-α, TGF-β and IL-8, at the optimal cut-off values (obtained from the receiver operating characteristic (ROC) curves), the calculated sensitivities are 46%, 72.97%, 67.56%, 54.05% and 83.8%, respectively. The simultaneous evaluation using all of the suggested markers resulted in increasing the sensitivity up to 100%. It thus recommended that, if patients with cirrhosis, as high risk patients, are subjected to regular examination using these markers in addition to AFP, HCC may be detected by 100% sensitivity in an early stage and as a consequence an effective treatment can be achieved.


Taila Dāha (Cauterization with Oil) an Innovative Approach in Pilonidal Sinus.
Summary: Pilonidal sinus is a chronic inflammatory track in mid gluteal cleft usually associated with hairs with an incidence rate of twenty six per one lakh population. It is more prevalently seen in the natal cleft of hairy middle aged obese, males. Such type of non-healing tracts may be considered as Nāḍivraṇa (Sinuses) and can either be treated by the conventional Kṣārasūtra (medicated seton) therapy or contemporary treatment methods. Irrespective of whatsoever management protocol adopted, it inevitably needs long term hospitalisation and is associated with complications. A case of a 28 year old male patient, presenting with pain (within tolerable limits) in the natal cleft and frequent occurrence of a pustule which burst out spontaneously on and off, diagnosed as pilonidal sinus (nāḍi vraṇa) was treated with excision of tract and Tailadāha (thermal cauterization with hot oil) with a combination of yaṣṭimadhu taila and powdered Copper Sulphate (CuSO4). Good haemostasis and uneventful wound healing with a minimally invasive and cost effective treatment was the outcome of study. This study represents an innovative treatment modality in pilonidal sinus.


Constant and continuous growth reduction as a possible cause of ageing.
Post-embryonic growth is characterized by a constant reduction of some growth parameters in relation to other growth parameters. Comparison of growth in chickens, rats and nematodes reveals an identical growth pattern, so a theory about the growth process in general is presented. It is presumed that the same growth promoting and growth inhibiting substances regulate not only growth but also ageing and that it is the equilibrium between growth promoters and growth inhibitors which is constantly changed.


Comparison of the severity of metabolic, liver and cardiovascular damage in NAFLD patients attending the hepatology clinic over the last three decades.
NAFLD prevalence is increasing worldwide. to assess whether severity of hepatic, metabolic and cardiovascular (CV) disease changed over time. 422 NAFLD patients (388 biopsy proven and 34 clinical cirrhosis) diagnosed between 1990 and 2021 and subdivided according to decade of presentation. Metabolic parameters, early atherosclerosis (carotid plaques at Doppler ultrasound), severity of liver damage (NAS score, NASH, significant fibrosis (≥2) and cirrhosis) and PNPLA3 genotyping were assessed. No difference in age, sex and prevalence of dyslipidemia and hypertension was found across decades (p for trend), whereas a higher prevalence of diabetes (p = 0.02), obesity (p<0.001), histological severe steatosis (p<0.001), NASH (p<0.001), fibrosis ≥2 (p<0.001), cirrhosis (p<0.001) and carotid plaques (p = 0.05) was observed in the last decade compared to the others. A higher prevalence of PNPLA3 GG polymorphism was found over time (p = 0.02). In the whole cohort, age, metabolic alterations and PNPLA3 G homozygosity were independent risk factors for hepatic fibrosis and carotid plaques, independently of the decade considered. Over the past 10 years compared to previous decades, NAFLD patients presented to observation with more severe liver disease and subclinical atherosclerosis, paralleling the spread of diabetes and obesity. PNPLA3 unfavorable genotype became more prevalent over time.


Accelerator Mass Spectrometry: Ultra-sensitive Detection Technique of Long-lived Radionuclides.
An introduction is given to accelerator mass spectrometry (AMS) technology, to the fundamental measurement principles, and the physics aspects behind the design constrain of AMS instruments. This article shall give an overview on technical design constraints of AMS instrumentation, general ion optical principles, and nuclide specific problems. The historic development of AMS detection techniques is briefly summarized. The wide variety of applications connected to the AMS technology are not discussed.


Receptor characteristics of the rat mammary carcinoma cell line 64-24.
Saturable binding of androgens, glucocorticoids, and triiodothyronine was found in the 64-24 hormone-responsive rat mammary carcinoma cell line. Androgen receptors had a dissociation content (Kd) for methyltrienolone of 3.4 X 10(-10) M and a binding capacity of approximately 10,000 sites/cell in whole cells. 5 alpha-[3H]dihydrotestosterone (DHT) was specifically taken up into approximately 2,150 nuclear sites with an affinity of 8.3 X 10(-10) M when nuclei were isolated from whole cells incubated with [3H]DHT. Sucrose gradient centrifugation of cytosol prepared from these cells revealed a displaceable [3H]DHT-binding component which migrated at 8S. Sedimentation analysis with high salt gradients of nuclear extracts from cells incubated with [3H]DHT revealed a peak of radioactivity in the 4S region which was abolished by coincubation of the cells with excess nonradioactive methyltrienolone. Receptors for [3H]dexamethasone were more abundant (approximately 50,000 sites/cell) in whole cells and had a Kd of 7.5 X 10(-9) M, but the number of nuclear binding sites was similar to that for androgens. Specificity studies using unlabeled steroids showed that each of the two classes of steroid receptors had greater affinities for their appropriate hormones. High affinity receptors for estrogens and progestins were not detectable in these cells. Triiodothyronine receptors were demonstrable but at a very low binding capacity (1,100 sites/cell). The Kd of these receptors was 0.6 X 10(-10) M. Cytogenetic studies revealed 44 chromosomes/mitosis with several unique markers. These receptor and karyotypic features suggest that the 64-24 cells may be useful in studying androgen action on breast cancer independently of estrogen or progestin influence, as well as the effects of thyroid hormone and glucocorticoids on breast cancer cells.


Tragedy of the commons in Melipona bees revisited.
Melipona stingless bees display a paradoxical overproduction of queens, which are later eliminated by nest-mate workers. Mechanistically, it was suggested that the monoterpenoid geraniol deposited into newly provisioned cells by adult bees would cause larvae to develop into queens in Melipona beecheii. This system could be evolutionarily stable if many of these new queens were to leave the nest and parasitize other genetically unrelated colonies nearby, as was shown to occur in a congeneric species. Here, we use microsatellite markers to test whether queen overproduction could be a strategy by which adult workers control the caste fate of the developing larvae to export copies of their own genes to the rest of the population via queen parasitism in M. beecheii. In addition, we re-examined whether artificially increasing the levels of geraniol indeed caused larvae to develop as queens rather than workers. Contrary to our prediction, we found no evidence for queen parasitism in M. beecheii and observed no effect of geraniol on the rearing of new queens. Together, these results support the original 'tragedy of the commons' hypothesis for queen overproduction in Melipona bees, where individual larvae selfishly bias their development towards the queen pathway according to their best evolutionary interests.


[Malaria prophylaxis; advice for the individual traveller. The Working Group for Malaria Prophylaxis].
Recently, the Dutch Working Group on Malaria Prophylaxis produced new national guidelines. The new approach takes the risk of malaria and of serious morbidity or mortality for the individual traveller as its point of departure. In large areas in the tropics, there is no malaria risk. In some areas with limited risk, proguanil is still an effective chemoprophylactic (mainly in Central America, the Near East, Central Asia and parts of Indonesia). However, multiple-drug resistant Plasmodium falciparum necessitates the use of mefloquine, despite disturbing side effects in some people, in Sub-Saharan Africa, major parts of South East Asia and the Amazone basin of South America. If mefloquine is contraindicated, alternatives advised are the combination of proguanil and chloroquine or (in South East Asia) doxycycline. For visits to transmission areas lasting 7 days or less, alternative prophylactic measures may be acceptable, but only if the traveller after the visit has easy access to adequate medical facilities. When exposure lasts not more than two nights, use of a mosquito net, repellents and protective clothing without chemoprophylaxis is acceptable, provided the traveller is well informed. To take along pocket treatment is only advised for some journeys lasting more than one month to areas with multiple-drug resistant falciparum malaria. When mefloquine prophylaxis is used, such stand-by treatment is only advocated for a few countries in South East Asia; when mefloquine cannot be given, also for other areas. The type of pocket treatment recommended depends on the chemoprophylaxis used and on whether contraindications exist. Drugs that can be used are: halofantrine (if no contraindications exist and an ECG shows no prolongation of the QT interval) or quinine, either alone (in pregnancy) or combined with doxycycline or clindamycine (the latter for children < 8 years). With the new individual approach advice may differ for different persons visiting similar tropical areas. It is the physician's task to explain the risks of a particular journey and the measures advised.


CT angiography in non-traumatic subarachnoid hemorrhage: the importance of arterial attenuation for the detection of intracranial aneurysms.
Computed tomography angiography (CTA) is today the primary method for the detection of intracranial aneurysms. The technique has evolved considerably during the last decade, and it is important to establish criteria for high image quality, especially with regard to improving the diagnosis of small aneurysms. To evaluate diagnostic accuracy and image quality by arterial attenuation of CTA in patients with non-traumatic subarachnoid hemorrhage (SAH). Between 2005 and 2011, CTA and digital subtraction angiography (DSA) were performed in 326 patients with non-traumatic SAH. Sensitivity and specificity for aneurysm detection were evaluated per patient, per aneurysm, and per ruptured aneurysm. The image quality of CTA was evaluated by arterial attenuation measurements (mean Hounsfield units [HU]) in the internal carotid artery (ICA). In all, 285 aneurysms in 235 patients were detected by DSA, 19 aneurysms were missed on CTA, and 223 aneurysms were classified as ruptured. In 91 patients, no aneurysm was found. Correct diagnosis with CTA was made in 28 patients with perimesencephalic hemorrhage. Sensitivity and specificity (95% confidence interval) calculated per patient were 91.6% (87.3-94.9) and 87.9% (79.8-93.6), respectively, per aneurysm 93.3% (89.7-95.9) and 88% (79.9-93.6), and per ruptured aneurysm 94.9% (91.3-97.3) and 96.7% (90.7-99.3). Arterial attenuation (in HU) in CTA revealing true positive ruptured aneurysms and true negative aneurysms (mean 535 ± 110 HU) differed significantly (P = 0.02) from false negative ruptured aneurysms (mean 424 ± 30 HU). CTA has high sensitivity and specificity for the detection of ruptured aneurysms. The sensitivity is related to arterial attenuation in the ICA.


A practical framework for regulating for-profit recreational marijuana in US States: Lessons from Colorado and Washington.
Despite the federal prohibition against marijuana, state-level recreational use appears to be moving forward. Public opinion is shifting. Following well-publicized state-legalization in Washington and Colorado, states across the US have begun considering similar measures. Since the 2016 election, over 21% of Americans now live in places where recreational marijuana is state-legal, and over 63% of the country permits medical or recreational use at the state level. This paper does not consider whether states should legalize marijuana nor does it weigh all regulatory options available to states. Instead, it considers how states can create a practical framework to regulate recreational marijuana, particularly in a climate of federal uncertainty where marijuana remains illegal. We draw lessons from Colorado and Washington-assuming that other states will adopt similar models and employ commercial, for-profit systems. Considering both the variety of goals that states could adopt and how they interact, we offer recommendations in five areas: cultivation, production, and processing; sale, consumption, and possession; taxes and finance; public health and safety; and governance. We recommend that states implement a relatively restrictive regulatory approach, with a single market for recreational and medical marijuana, if appropriate. This should make marijuana laws easier to enforce, help reduce diversion, and satisfy federal guidance. Moreover, drawing from Colorado and Washington's experience, we suggest a flexible system with robust data collection and performance monitoring that supports a thorough evaluation. This should allow states to "learn as they go"-a must, given the uncertainty surrounding such policy shifts. Of course, a tightly regulated approach will have drawbacks-including a significant illegal market. But political experience teaches that states will be better off loosening a tight market than attempting to tighten a loose one. We also consider a potential role for the federal government under the status quo.


Tuneable Plasmonic Resonances Of A Dynamic Thin Film Of Ultrasmall Nanocrystals Modified In the Anti-Galvanic Reduction Process.
Ultrasmall gold nanoparticles (NPs) have revolutionized nanotechnology as they are an excellent starting substrate for the synthesis of organic-inorganic hybrid materials with photonic or energy conversion applications, often with a responsive nature. However, ultrasmall NPs do not sustain plasmonic resonances, preventing their use in plasmon-related applications. In the presented work, we show a method of chemical modification of ultrasmall gold nanoparticles in order to fabricate dynamically controlled plasmonic thin films. For this purpose, we used the Anti-Galvanic Reduction process (AGR) to modify the surface of small gold nanoparticles, inducing plasmonic properties without notable size increases. Au@Ag NPs are then modified with liquid crystal-like organic ligands. The obtained NPs can assemble into densely packed films with long-range order and temperature-dependent structural properties. Namely, we detect two, fully reversible phase transitions between the hexagonal and cubic symmetries. The combination of AGR and organic surface modifications enabled us to demonstrate the possibility of managing plasmonic properties in the thin film of ~2 nm diameter metallic NPs.


Symptomatic floaters as a clue to vitreoretinal disease.
One hundred consecutive patients with symptomatic floaters without previous ocular trauma or surgery are analyzed as to the underlying cause. The most common findings were posterior vitreous detachment with and without vitreous hemorrhage, vitreous syneresis with collagen fibril clumping, diabetic retinopathy with vitreous hemorrhage, retinal tears without retinal separation, and retinal separation. Significant vitreoretinal disease occurred in 36% of the patients.


A novel method for the normalization of microRNA RT-PCR data.
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate mRNA transcript levels and translation. Deregulation of microRNAs is indicated in a number of diseases and microRNAs are seen as a promising target for biomarker identification and drug development. miRNA expression is commonly measured by microarray or real-time polymerase chain reaction (RT-PCR). The findings of RT-PCR data are highly dependent on the normalization techniques used during preprocessing of the Cycle Threshold readings from RT-PCR. Some of the commonly used endogenous controls themselves have been discovered to be differentially expressed in various conditions such as cancer, making them inappropriate internal controls. We demonstrate that RT-PCR data contains a systematic bias resulting in large variations in the Cycle Threshold (CT) values of the low-abundant miRNA samples. We propose a new data normalization method that considers all available microRNAs as endogenous controls. A weighted normalization approach is utilized to allow contribution from all microRNAs, weighted by their empirical stability. The systematic bias in RT-PCR data is illustrated on a microRNA dataset obtained from primary cutaneous melanocytic neoplasms. We show that through a single control parameter, this method is able to emulate other commonly used normalization methods and thus provides a more general approach. We explore the consistency of RT-PCR expression data with microarray expression by utilizing a dataset where both RT-PCR and microarray profiling data is available for the same miRNA samples. A weighted normalization method allows the contribution of all of the miRNAs, whether they are highly abundant or have low expression levels. Our findings further suggest that the normalization of a particular miRNA should rely on only miRNAs that have comparable expression levels.


DeepMoCap: Deep Optical Motion Capture Using Multiple Depth Sensors and Retro-Reflectors.
In this paper, a marker-based, single-person optical motion capture method (DeepMoCap) is proposed using multiple spatio-temporally aligned infrared-depth sensors and retro-reflective straps and patches (reflectors). DeepMoCap explores motion capture by automatically localizing and labeling reflectors on depth images and, subsequently, on 3D space. Introducing a non-parametric representation to encode the temporal correlation among pairs of colorized depthmaps and 3D optical flow frames, a multi-stage Fully Convolutional Network (FCN) architecture is proposed to jointly learn reflector locations and their temporal dependency among sequential frames. The extracted reflector 2D locations are spatially mapped in 3D space, resulting in robust 3D optical data extraction. The subject's motion is efficiently captured by applying a template-based fitting technique on the extracted optical data. Two datasets have been created and made publicly available for evaluation purposes; one comprising multi-view depth and 3D optical flow annotated images (DMC2.5D), and a second, consisting of spatio-temporally aligned multi-view depth images along with skeleton, inertial and ground truth MoCap data (DMC3D). The FCN model outperforms its competitors on the DMC2.5D dataset using 2D Percentage of Correct Keypoints (PCK) metric, while the motion capture outcome is evaluated against RGB-D and inertial data fusion approaches on DMC3D, outperforming the next best method by 4 . 5 % in total 3D PCK accuracy.


Evaluating the impact of a street outreach intervention on participant involvement in gun violence.
The past several years have witnessed increased calls for community violence interventions (CVIs) that address firearm violence while centering local expertise and avoiding the criminal legal system. Currently, little evidence exists on CVI effectiveness at the individual level. This study presents an evaluation of the impact of a street outreach-based CVI [Chicago CRED (Create Real Economic Destiny)] on participant involvement in violence. We used a quasiexperimental design with a treatment sample of 324 men recruited by outreach staff from 2016 to 2021 and a balanced comparison sample of 2,500 men from a network of individuals arrested in CRED's service areas. We conducted a Bayesian survival analysis to evaluate CRED's effect on individual violence-related outcomes on three levels of treatment: All enrolled participants, a subsample that made it through the initial phase, and those who completed programming. The intervention had a strong favorable effect on the probability of arrest for a violent crime for those completing the program: After 24 mo, CRED alumni experienced an 11.3 percentage point increase in survival rates of arrest for a violent crime relative to their comparisons (or, stated differently, a 73.4% reduction in violent crime arrests). The other two treatment levels experienced nontrivial declines in arrests but did not reach statistical significance. No statistically significant reduction in victimization risk was detected for any of the treatment levels. Results demonstrate that completion of violence intervention programming reduces the likelihood of criminal legal involvement for participants, despite the numerous systemic and environmental factors that impede personal success.


Evaluation of the clinical and prognostic importance of infection parameters in thyroid cancers: A cross-sectional study.
Thyroid cancers are among the most common endocrine cancers. An inflammation is associated with many stages of cancer. Therefore, in this study, we aimed to evaluate whether it has a prognostic significance inflammation marker. Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio, systemic inflammation response, systemic immune-inflammation index, and neutrophils to lymphocytes and platelets ratio (N/LP) in patients diagnosed with thyroid cancer in the internal medicine outpatient clinic and operated between March 1, 2017 and May 1, 2022 were evaluated retrospectively. Three hundred forty patients were diagnosed with thyroid cancer; 275 (80.9%) of them were women and the mean age was 44.6 ± 13.5 years. Multifocality (P = .02) was significant in patients with invasion. High N/LP ratio (odds ratio: 1.4, 95% confidence interval: 1.0-2.0, p: 0.003) and high invasion (odds ratio: 0.2, 95% confidence interval: 0.1-0.4, P < .01) was found to be significant in patients with tumor size ≥2 cm. There is a relationship between multifocality and invasion, and the risk of invasion increases as the tumor size increases in thyroid cancer. The N/LP ratio was significant as it could be a new marker in showing the relationship between thyroid cancer and its prognosis. Further studies are needed in which the prognosis is followed up, longer-term, more comprehensive, and confounding factors are excluded.


Long-term rearing of Arctic charr Salvelinus alpinus under different salinity regimes at constant temperature.
Arctic charr Salvelinus alpinus of the Hólar strain (mean ± s.e. body mass = 152·1 ± 3·1 g) were reared at four different salinity regimes at a constant temperature of 7·4° C. Two groups were given a three-month acclimation in salinity 18 before the salinity was increased to either 25 or 29 (groups called A25 and A29), and two groups were reared in salinities 25 or 29 over the full experimental period of 409 days (groups called F25 and F29). In the first 3 months, the A25 and A29 groups had the highest growth rates. By October 2011, there were no significant differences (two-way nested ANOVA, P > 0·05) in the mean body masses among A25, F25 and F29 (c. 1450 g), whereas A29 had a lower mean mass (1282 g). The growth in the last period from October 2011 to January 2012 was reduced by sexual maturation in the highest salinity regimes (A29 and F29), whereas fish in groups A25 and F25 showed high growth throughout the study. Males in all salinity groups had higher growth rates than females for the most part of the study, but the divergence between the sexes was most pronounced in the highest salinity regimes. All salinity groups showed distinct changes in Na(+) , K(+) -ATPase activity, with high activity in spring and summer, and lower activity in the autumn. Plasma sodium (Na(+) ) levels were stable indicating that none of the experimental groups had problems in maintaining hydromineral balance during the study. While plasma leptin levels were not affected by salinity regimes, it was noted that these levels were 13-30% higher in fish with empty guts compared with those having food in their gut at the time of sampling. This suggests a link between leptin levels and food intake, indicating that this hormone may play a role in food intake and energy allocation in fishes.


[Becoming pregnant and maintaining pregnancy].
To begin with, a brief historical review of a number of features of bovine fertility is presented in the present paper which is part of the series 'Papers of Yesterday and Today'. This is followed by a discussion of the current situation. All this is done on the basis of a paper by Stockfleth which appeared in 1878. As a result of the eradication of venereal infections and brucellosis, becoming pregnant as well as pregnancy run a course associated with less problems than it was one hundred years earlier. Errors of herd management are immediately reflected in fertility. When animals fail to stay pregnant (abortion), a large number of possible causes may be suggested. Infections are among the most important of these causes. Finally, attempts are made to look into the future. Becoming pregnant will probably run a more difficult course in view of the fact that getting the cycles going post-partum in highly productive cows gives rise to additional problems. As regards staying pregnant, considerable changes are not anticipated.


Nucleotide sequence analysis of RepFIC, a basic replicon present in IncFI plasmids P307 and F, and its relation to the RepA replicon of IncFII plasmids.
RepFIC is a basic replicon of IncFI plasmid P307 which is located within a 3.09-kilobase SmaI fragment. The nucleotide sequence of this region has been determined and shown to be homologous with the RepFIIA replicon of IncFII plasmids. The two replicons share three homologous regions, HRI, HRII, and HRIII, which are flanked by two nonhomologous regions, NHRI and NHRII. A comparison of coding regions reveals that the two replicons have several features in common. RepFIC, like RepFIIA, codes for a repA2 protein with its amino-terminal codons in HRI and its carboxy-terminal codons in NHRI. Although the codons for the repA1 proteins are located in NHRII, the DNA region containing a putative promoter, ribosomal binding site, and initiation codons is located in HRII. This region also codes for an inc RNA. There are nine base-pair differences between the inc RNA of RepFIIA and that of RepFIC, and as a result, RepFIC and RepFIIA replicons are compatible. An EcoRI fragment from the F plasmid which shows homology with RepFIC of P307 has also been sequenced. This fragment contains only a portion of RepFIC, including the genes for the putative repA2 protein and inc RNA. The region coding for a putative repA1 protein is interrupted by the transposon Tn1000 and shows no homology with the repA1 region of RepFIIA and RepFIC of P307. Our comparative and structural analyses suggest that RepFIC and RepFIIA, although different, have a similar replication mechanism and thus can be assigned to the same replicon family, which we designate the RepFIIA family.


Elucidation of the DNA sequence preferences of daunomycin.
The sequence specificity of daunomycin was assessed using competition equilibrium dialysis, DNAse I footprinting and an E. coli RNA polymerase transcription inhibition assay; similar studies were performed on adriamycin and a new bis-intercalating daunomycin dimer. The results clearly demonstrate that the highest affinity sites are CA for daunomycin and adriamycin, and CACA for the bis-daunomycin. Other modest affinity (GC, CG, CT, TC, CC, AC) and poor affinity binding sites (AA, AT, TA) were also observed. Our results are in agreement with (a) the observed 5'-pyrimidine-purine-3' sequence preference of intercalating drugs, (b) the reported role played by OH(9) of daunomycin in the stabilization of the drug/DNA intercalation complex, and (c) the thermodynamics of nearest neighbour base-pair unstacking at the intercalation site. The CA specificity of daunomycin and adriamycin suggests that their biological activity may arise from association with the CA containing sequences which are thought to be associated with genetic regulatory elements in eukaryotes. The implications for future anthracycline drug design are presented in this context.


Retrospective assessment of initial stroke severity: comparison of the NIH Stroke Scale and the Canadian Neurological Scale.
The NIH Stroke Scale (NIHSS) and the Canadian Neurological Scale (CNS) have been reported to be useful for the retrospective assessment of initial stroke severity. However, unlike the CNS, the NIHSS requires detailed neurological assessments that may not be reflected in all patient records, potentially limiting its applicability. We assessed the reliability of the retrospective algorithms and the proportions of missing items for the NIHSS and CNS in stroke patients admitted to an academic medical center (AMC) and 2 community hospitals. Randomly selected records of patients with ischemic stroke admitted to an AMC (n=20) and community hospitals with (CH1, n=19) and without (CH2, n=20) acute neurological consultative services were reviewed. NIHSS and CNS scores were assigned independently by 2 neurologists using published algorithms. Interrater reliability of the scores was determined with the intraclass correlation coefficient, and the numbers of missing items were tabulated. The intraclass correlation coefficient for NIHSS and CNS, respectively, were 0.93 (95% CI, 0.82 to 1.00) and 0.97 (95% CI, 0.90 to 1.00) for the AMC, 0.89 (95% CI, 0.75 to 1.00) and 0.88 (95%, 0.73 to 1.00) for the CH1, and 0.48 (95% CI, 0.26 to 0.70) and 0.78 (95% CI, 0.60 to 0.96) for the CH2. More NIHSS items were missing at the CH2 (62%) versus the AMC (27%) and the CH1 (23%, P:=0.0001). In comparison, 33%, 0%, and 8% of CNS items were missing from records from CH2, AMC, and CH1, respectively (P:=0.0001). The levels of interrater agreement were almost perfect for retrospectively assigned NIHSS and CNS scores for patients initially evaluated by a neurologist at both an AMC and a CH. Levels of agreement for the CNS were substantial at a CH2, but interrater agreement for the NIHSS was only moderate in this setting. The proportions of missing items are higher for the NIHSS than the CNS in each setting, particularly limiting its application in the hospital without acute neurological consultative services.


Phase variation of Andrewes in Salmonella enteritidis bioserotype paratyphi-A.
The natural occurrence of a strain of Salmonella enteritidis bioserotype Paratyphi-A is reported, in which the flagellar antigens segregated readily into normal phase 2 antigens and mixtures of normal phase 1 and phase 2 antigens, and in which phase variation of Andrewes was demonstrated with ease.


Epidemiological evidence of higher susceptibility to vCJD in the young.
The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD) cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE) epidemic may provide a simpler explanation. Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD), we examine whether the age characteristics of vCJD cases may be reproduced. The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%. This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases.


[The availability and quality of the ambulatory polyclinic care].
The article deals with the results of the study of complex of medical demographic and social economic indicators of Nizhny Novgorod oblast during 1989-2010. The results are as follows. The policlinics' net reduced by 2.25 times, including by 10.6 times in rural area and by 12.6 times of ambulatories of community hospitals. The indicators of physicians' supply of oblast population decreased too especially in urban area. The annual number of visits to physicians per capita decreased by 1.36 times. The number of calls of out-patients to physicians of emergency medical care increased by 1.5 times. The morbidity with temporarily disability and primary registration as a disabled person decreased by 1.45 times, including able-bodied citizen by 1.54 times. In Nizhny Novgorod oblast, the rate of decrease of indicators of primary disability during 2006-2009 overpassed the corresponding federal indicators by 1.45 times. The population mortality increased by 1.43 times. The accessibility and quality of ambulatory polyclinic care significantly impacts on the levels of mortality and social security of population and can be used as an indicator of social risks in the region.


Sorting mesoscopic objects with periodic potential landscapes: optical fractionation.
Viscously damped objects driven through a periodically modulated potential energy landscape can become kinetically locked in to commensurate directions through the landscape, and thus can be deflected away from the driving direction. We demonstrate that the threshold for an object to become kinetically locked in to an array can depend exceptionally strongly on its size. When implemented with an array of holographic optical tweezers, this process provides the basis for a continuous and continuously optimized sorting technique for mesoscopic objects called "optical fractionation."


Protein composition and activation markers in plasma collected by three apheresis procedures.
Scientific and technical advances made in transfusion medicine sustain the need for more comprehensive understanding of the impact of collection procedures on the quality of plasma for fractionation and for transfusion. This prospective work evaluated protein composition and markers of activation in plasma donations collected with three different automatic collection procedures (performed on Haemonetics machines), including a new procedure using a high-separation core-molded bowl. A total of 90 collection procedures have been performed from a population of 37 donors, under comprehensively standardized conditions. Plasma aliquots were taken from the plasma units within 30 minutes of the end of the collection procedures and immediately frozen at -70 degrees C. Content in an extended range of proteins and of markers of activation of the coagulation and fibrinolytic systems has been measured using standard in vitro testing methods. Plasma donations had normal mean total protein, IgG, IgM, and fibrinogen content. The mean levels in coagulation FV, FVII, FVIII, and FXI and in antithrombin were above the standard international requirements. There was no sign of activation of the hemostasis system, as assessed by activated FVII, thrombin antithrombin complex, Prothrombin fragment 1+2, and D-dimers. Activated complement component C3 and C5 were low. Data indicates the good and consistent protein composition of plasma obtained by those automatic apheresis procedures. In particular, the new high-separation core procedure yields a high-quality plasma meeting requirements for transfusion and fractionation.


Appendicitis within an umbilical hernia sac: previously unreported complication in children.
Umbilical hernia is one of the most common congenital pathologies of the anterior abdominal wall in children. Umbilical hernia in children has a high tendency for spontaneous closure. Surgical treatment is performed only for rarely occurring complications. Appendicitis within an umbilical hernia sac is a previously unreported complication for umbilical hernias. We report here the first case in the current English language literature.


Work remains meaningful despite time out of the workplace and chronic pain.
Although work has been found to be meaningful and a source of motivation to return to work in certain disabled populations, it was unclear if this was also true for people experiencing a long period of unemployment and job loss due to a musculoskeletal injury. Therefore, the aim of this phenomenological study was to explore the meaning of work for those with chronic work disability due to a musculoskeletal injury. The data from 27 interviews, conducted with 9 participants, was analyzed using the Empirical Phenomenological Psychological method. Work remained central to the lives of the participants and aligned with previous valued work outcomes and goals regardless of the amount of time away from work. These findings point to the importance of recognizing the ongoing centrality of work for those with chronic work disability and the importance of tapping into work values and beliefs to provide workers with the motivation needed to get past physical and systemic barriers to return to work. This study shows that a shift in focus back to meaning not only has benefits for people with chronic work disability, but for occupational therapists in their ability to make a unique and effective contribution to the field of work disability. Implications for rehabilitation The chronic work disabled population remains one of the most challenging to return to work. Reflection on the meaning of work provides motivation needed for clients to overcome barriers to work including chronic pain. Exploring meaning is not difficult or time consuming in vocational rehabilitation.


Multi-year evolutionary dynamics of West Nile virus in suburban Chicago, USA, 2005-2007.
West Nile virus has evolved in concert with its expansion across North America, but little is known about the evolutionary dynamics of the virus on local scales. We analysed viral nucleotide sequences from mosquitoes collected in 2005, 2006, and 2007 from a known transmission 'hot spot' in suburban Chicago, USA. Within this approximately 11 x 14 km area, the viral envelope gene has increased approximately 0.1% yr(-1) in nucleotide-level genetic diversity. In each year, viral diversity was higher in 'residential' sites characterized by dense housing than in more open 'urban green space' sites such as cemeteries and parks. Phylodynamic analyses showed an increase in incidence around 2005, consistent with a higher-than-average peak in mosquito and human infection rates that year. Analyses of times to most recent common ancestor suggest that WNV in 2005 and 2006 may have arisen predominantly from viruses present during 2004 and 2005, respectively, but that WNV in 2007 had an older common ancestor, perhaps indicating a predominantly mixed or exogenous origin. These results show that the population of WNV in suburban Chicago is an admixture of viruses that are both locally derived and introduced from elsewhere, containing evolutionary information aggregated across a breadth of spatial and temporal scales.


lncRNA SNHG3 acts as a novel Tumor Suppressor and regulates Tumor Proliferation and Metastasis via AKT/mTOR/ERK pathway in Papillary Thyroid Carcinoma.
The incidence of papillary thyroid carcinoma (PTC) has been increased rapidly in recent decades. Long noncoding RNAs (lncRNA) are a class of non-protein-coding transcripts and play critical roles in regulating gene expression and influence biological behaviors of multiple cancers, including PTC. Here, we discovered that lncRNA SNHG3 was significantly downregulated in PTC tissues and cell lines, the expression of SNHG3 was negatively correlated with the TNM stage and poor prognosis of PTC patients. Functional studies illustrated that the depletion of SNHG3 via CRISPR/Cas9 technology promoted the proliferation, migration and invasion abilities of PTC cells. Tumor xenograft models confirmed the tumor-promoting role of silenced SNHG3 in vivo. Further mechanistic analyses revealed that knockout of SNHG3 activated the AKT/mTOR/ERK pathway in PTC cell lines and the mTOR inhibitor AZD8055 abrogated the tumor-promoting effect induced by SNHG3 inhibition. Taken together, our findings identified a lncRNA SNHG3 that functions its tumor-suppressor role during PTC development and SNHG3 might serve as a promising candidate for target therapy of PTC.


Origin of amphibian and avian chromosomes by fission, fusion, and retention of ancestral chromosomes.
Amphibian genomes differ greatly in DNA content and chromosome size, morphology, and number. Investigations of this diversity are needed to identify mechanisms that have shaped the evolution of vertebrate genomes. We used comparative mapping to investigate the organization of genes in the Mexican axolotl (Ambystoma mexicanum), a species that presents relatively few chromosomes (n = 14) and a gigantic genome (>20 pg/N). We show extensive conservation of synteny between Ambystoma, chicken, and human, and a positive correlation between the length of conserved segments and genome size. Ambystoma segments are estimated to be four to 51 times longer than homologous human and chicken segments. Strikingly, genes demarking the structures of 28 chicken chromosomes are ordered among linkage groups defining the Ambystoma genome, and we show that these same chromosomal segments are also conserved in a distantly related anuran amphibian (Xenopus tropicalis). Using linkage relationships from the amphibian maps, we predict that three chicken chromosomes originated by fusion, nine to 14 originated by fission, and 12-17 evolved directly from ancestral tetrapod chromosomes. We further show that some ancestral segments were fused prior to the divergence of salamanders and anurans, while others fused independently and randomly as chromosome numbers were reduced in lineages leading to Ambystoma and Xenopus. The maintenance of gene order relationships between chromosomal segments that have greatly expanded and contracted in salamander and chicken genomes, respectively, suggests selection to maintain synteny relationships and/or extremely low rates of chromosomal rearrangement. Overall, the results demonstrate the value of data from diverse, amphibian genomes in studies of vertebrate genome evolution.


No sex differences in adult telomere length across vertebrates: a meta-analysis.
In many mammalian species, females live on average longer than males. In humans, women have consistently longer telomeres than men, and this has led to speculation that sex differences in telomere length (TL) could play a role in sex differences in longevity. To address the generality and drivers of patterns of sex differences in TL across vertebrates, we performed meta-analyses across 51 species. We tested two main evolutionary hypotheses proposed to explain sex differences in TL, namely the heterogametic sex disadvantage and the sexual selection hypotheses. We found no support for consistent sex differences in TL between males and females among mammal, bird, fish and reptile species. This absence of sex differences in TL across different classes of vertebrates does not support the heterogametic sex disadvantage hypothesis. Likewise, the absence of any negative effect of sexual size dimorphism on male TL suggests that sexual selection is not likely to mediate the magnitude of sex differences in TL across vertebrates. Finally, the comparative analyses we conducted did not detect any association between sex differences in TL and sex differences in longevity, which does not support the idea that sex differences in TL could explain the observed sex differences in longevity.


Prevalence of gastrointestinal complaints in runners competing in a long-distance run: an internet-based observational study in 1281 subjects.
To assess the prevalence, risk factors and timing of gastrointestinal (GI) complaints in a large group of runners competing in a long-distance run. GI symptoms indicating GI ischaemia were of specific interest. A questionnaire was sent by e-mail to 2076 athletes who had competed in a recreational run and 1281 (62% response rate) were returned. Reported GI complaints were related to variables such as age, gender, distance, fluid and food ingestion and running experience. For statistical analyses, chi(2) tests and logistic regression analyses were used. The run was completed by 98% of the runners. Three athletes dropped out because of GI complaints, 45% had at least one GI complaint during running, while 11% of the runners suffered from serious GI complaints during the run, the last mentioned being significantly related to runners who were not familiar with fluid ingestion, those of younger age, female gender and those who did not complete the run. Of the runners, 2.7% had complaints during the first 24 h after the run. This was significantly related to female gender and GI complaints during the run. The prevalence of GI complaints during and after running was low compared with that reported in other studies, which is partly due to the definition of "symptomatic" used in our study. The risk factors associated with becoming symptomatic were identical to those in other studies. The relationship between complaints during the run and the type of complaints afterwards suggests a role of GI ischaemia in the pathophysiology of running-induced GI symptoms.


Gait Pattern Recognition Based on Supervised Contrastive Learning Between EEG and EMG.
Electroencephalography (EEG) and lower-limb electromyography (EMG) signals are widely used in lower-limb kinematic classification and regression tasks. Since it directly measures muscle responses, EMG usually works better. However, due to the susceptibility of EMG signals to muscle fatigue, insufficient residual myoelectric activity, and the difficulty of precise localization, it is difficult to acquire EMG signals in practice. In contrast, EEG signals are stable and easy to sample. Therefore, in this work, we propose a multimodal training strategy based on supervised contrastive learning. With this training strategy, we can effectively use the guiding role of EMG in the training phase to help the model fit the gait with EEG signal while using only EEG signal in the testing phase to obtain better results than using any single modal signal to train and test the model. Finally, we compared the models trained with the strategy proposed in this paper with other models trained with EEG signals. The obtained Pearson's Correlation Coefficient value exceeds those of all baseline models.


Barriers to accessing HIV services for Black African communities in Cambridgeshire, the United Kingdom.
The majority of new HIV diagnoses in the United Kingdom (UK) occur in people with heterosexually acquired HIV infection, the majority of whom are African communities. Current research shows that despite health promotion efforts and advances in therapy these communities are accessing HIV care late. This study therefore explored barriers to equal access to HIV services by African migrants in the UK. Kleinman's (Patients and healers in the context of culture: an exploration of the borderland between anthropology, medicine, and psychiatry, vol 3. University of California Press, Berkeley, 1980) model of health care systems was applied in this research as a theoretical framework and lens through which the reported findings are viewed as it places health within the broader context of culture. In this research a qualitative approach with focus groups was used. A total of thirty participants were recruited from African migrant community organisations in Cambridgeshire in the East of England strategic health authority in order to study the experiences of African migrants when accessing sexual health services. It was found that barriers to equal access to HIV services exist for African communities in Cambridgeshire. These included language barriers and others bordering on the use of traditional medicine by African migrants, understanding of cultural diversity, awareness of how and where to access HIV services, and getting information about HIV. Findings highlighted the importance of taking the sectors of Kleinman's [1] model into consideration when planning HIV services for African communities.


Primate flicker sensitivity: psychophysics and electrophysiology.
A quantitative comparison is made between the psychophysical flicker response of man and similar data obtained electrophysiologically from the cones of macaque monkeys. When the psychophysical data are obtained from an eye that is strongly light-adapted, there is excellent agreement between the two sets of data at high frequencies. Under this condition, both kinds of data fit a distributed-parameter model, whose time constant also agrees with that derived from studies of the phosphenes elicited by electrical stimulation of the human eye. On the other hand, psychophysical data obtained with fully modulated stimuli (which minimally adapt the eye) yield a longer time constant for the same model. These results imply that the psychophysical flicker thresholds are normally controlled by a distributed filtering process that is proximal to the receptor stage. This slower, psychophysical process is evidently desensitized by intense adapting lights, so that the faster one that governs the electrophysiological responses can be detected.


Personalizing Psychological Care for Chronic Cancer-Related Fatigue: A Case Study on Symptom Dynamics.
Approximately 25% of cancer patients suffer from chronic cancer-related fatigue (CCRF), which is a complex, multifactorial condition. While there are evidence-based interventions, it remains unclear what treatment works best for the individual patient. Psychological network models can offer a schematic representation of interrelations among fatigue and protective and perpetuating factors for the individual patient. We explored whether feedback based on these individual fatigue networks can help personalize psychological care for CCRF. A 34-year old woman with CCRF was referred to our mental healthcare institute for psycho-oncology. During the waitlist period, she filled out an experience sampling app for 101 days, including five daily assessments of fatigue, pain, mood, activity and fatigue coping. The interplay between items was visualized in network graphs at the moment-level and day-level, which were discussed with the patient. For example, acceptance of fatigue in the past three hours was associated with less hopelessness and less fatigue in the following moment. At the day-level, acceptance was also being associated with less fatigue, less hopelessness, a better mood, and more motivation to do things. The patient recognized these patterns and explained how unexpected waves of fatigue can make her feel hopeless. This started a dialogue on how cultivating acceptance could potentially help her handle the fatigue. The patient would discuss this with her therapist. Feedback based on individual fatigue networks can provide direct insight into how one copes with CCRF and subsequently offer directions for treatment. Further research is needed in order to implement this in clinical practice.


Monohydrates of cuprous chloride and argentous chloride: H2O⋅⋅⋅CuCl and H2O⋅⋅⋅AgCl characterized by rotational spectroscopy and ab initio calculations.
Pure rotational spectra of the ground vibrational states of ten isotopologues of each of H(2)O⋅⋅⋅CuCl and H(2)O⋅⋅⋅AgCl have been measured and analyzed to determine rotational constants and hyperfine coupling constants for each molecule. The molecular structure and spectroscopic parameters determined from the experimental data are presented alongside the results of calculations at the CCSD(T) level. Both experiment and theory are consistent with structures that are nonplanar at equilibrium. The heavy atoms are collinear while the local C(2) axis of the water molecule intersects the axis defined by the heavy atoms at an angle, φ = 40.9(13)° for Cu and φ = 37.4(16)° for Ag. In the zero-point state, each molecule is effectively planar, undergoing rapid inversion between two equivalent structures where φ has equal magnitude but opposite sign. The equilibrium geometry has C(s) symmetry, however. The ab initio calculations confirm that the timescale of this inversion is at least an order of magnitude faster than that of rotation of the molecule in the lowest rotational energy levels. The molecular geometries are rationalized using simple rules that invoke the electrostatic interactions within the complexes. Centrifugal distortion constants, Δ(J) and Δ(JK), nuclear quadrupole coupling constants, χ(aa)(Cu), χ(aa)(Cl), (χ(bb) - χ(cc))(Cu), and (χ(bb) - χ(cc))(Cl), and the nuclear spin-rotation constant of the copper atom, C(bb)(Cu)+C(cc)(Cu), are also presented.


Long term sustained attention alters dynamic functional connectivity patterns.
Mental fatigue has attracted much attention from researchers as it plays a key role in performance efficiency and safety situations. Functional connectivity analysis using graph theory is an effective method for revealing changes in cognition resources influenced by mental fatigue. Previous studies have revealed that functional networks are dynamically reorganized. Therefore, it is critical to explore dynamic timescales of networks related to specific cognitive abilities. In this study, we used an open EEG dataset of twenty-one subjects recorded in a 60-minutes sustained attention task. After preprocessing, we constructed connectivity matrices using the weighted phase lag index (wPLI) in the theta band and characterized them with dynamic graph measures, namely characteristic path length (CPL) and clustering coefficient (CC). The results show that the frontal-parietal brain networks in theta band are involved in a sustaining attention task. When averaging from temporal and spatial activations, CPL and CC decreased with time-on-task. Our results indicate that mental fatigue results in deteriorations in sustaining attention, and graph theory analysis can provide support for mental fatigue analysis.Clinical Relevance- Identification of the effects of long term sustained attention on dynamic brain networks may be potential for mechanism study and detection of mental states and attentional deficits caused by mental diseases.


Performance enhancement of carbon nanotube thin film transistor by yttrium oxide capping.
Carbon nanotube thin film transistors (CNT-TFTs) are regarded as promising technology for active matrix pixel driving circuits of future flat panel displays (FPD). For FPD application, unipolar thin film transistors (TFTs) with high mobility (μ), high on-state current (ION), low off-current (IOFF) at high source/drain bias and small hysteresis are required simultaneously. Though excellent values of those performance metrics have been realized individually in different reports, the overall performance of previously reported CNT-TFTs has not met the above requirements. In this paper, we found that yttrium oxide (Y2O3) capping is helpful in improving both ION and μ of CNT-TFTs. Combining Y2O3 capping and Al2O3 passivation, unipolar CNT-TFTs with high ION/IOFF (>107) and low IOFF (∼pA) at -10.1 V source/drain bias, and relatively small hysteresis in the range of -30 V to +30 V gate voltage were achieved, which are capable of active matrix display driving.


Bionanotechnology application of polypeptides in a hair color product: self-assembly enables expression, processing, and functionality.
Bionanotechnology aims to impart new properties to materials from unique functionalities present in biomolecules. However, the promise of bionanotechnology has not materialized beyond the biomedical field due in large part to issues of scalability, purity, and cost of manufacturing. In this work we demonstrate an approach to co-engineer production and system functionality into a single polypeptide. We designed a system to anchor particles onto hair via a multifunctional polypeptide composed of two domains, one with affinity to hair and the other capable of strong interactions with the particle surface. These strong interactions, exemplified by resistance to anionic surfactants, stem from the ability to self-assemble into higher order structures, which were observed by atomic force microscopy. At the same time, the controlled solubility properties of the particle binding domain permit the scalable production in Escherichia coli via inclusion bodies and cost effective purification. We believe this is a significant advance toward the development of bionanotechnology for industrial applications.


[Disinhibition as a mechanism of tuning of cross-like figures in the visual cortex neurons].
A discrete neural net was used for simulation of cross-sensitivity in 40% of neurones of the cat visual cortex' area 17th. It is based on disinhibition of the end-stopping inhibition in receptive field from the side-disinhibitory zone. Highly selective or invariant sensitivity of the simulated neurone in respect to shape and orientation of a cross-like figure was observed under changes of location, size and weight of the receptive field zones. The disinhibitory mechanism seems to be critically involved in the selection of the second-order features of the images in the primary visual cortex.


Asian house rats may facilitate their invasive success through suppressing brown rats in chronic interaction.
The Asian house rat (Rattus tanezumi) and the brown rat (Rattus norvegicus) are closely related species and are partially sympatric in southern China. Over the past 20 years, R. tanezumi has significantly expanded northward in China and partially replaced the native brown rat subspecies, R. n. humiliatus. Although invasive species are often more aggressive than native species, we did not observe interspecific physical aggression between R. tanezumi and R. n. humiliatus. Here, we focused on whether or not R. tanezumi was superior to R. n. humiliatus in terms of nonphysical competition, which is primarily mediated by chemical signals. We performed two laboratory experiments to test different paradigms in domesticated R. tanezumi and R. n. humiliatus. In Experiment 1, we caged adult male rats of each species for 2 months in heterospecific or conspecific pairs, partitioned by perforated galvanized iron sheets, allowing exchange of chemical stimuli and ultrasonic vocalization. The sexual attractiveness of male urine odor showed a tendency (marginal significance) to increase in R. tanezumi caged with R. n. humiliatus, compared with those in conspecific pairs. Hippocampal glucocorticoid receptor (GR) and brain-derived nutrition factor (BDNF) mRNA were upregulated in R. n. humiliatus and R. tanezumi, respectively, when the rats were caged in heterospecific pairs. In Experiment 2, we kept juvenile male rats in individual cages in rooms with either the same or the different species for 2 months, allowing chemical interaction. The sexual attractiveness of male urine was significantly enhanced in R. tanezumi, but reduced in R. n. humiliatus by heterospecific cues and mRNA expression of hippocampal GR and BDNF were upregulated by heterospecific cues in R. n. humiliatus and R. tanezumi, respectively. Although not identical, the results from Experiments 1 and 2 were generally consistent. The results of both experiments indicate that nonphysical/chronic interspecific stimuli, particularly scent signals, between R. n. humiliatus and R. tanezumi may negatively affect R. n. humiliatus and positively affect R. tanezumi. We infer that chronic interspecific interactions may have contributed to the invasion of R. tanezumi into the range of R. n. humiliatus in natural habitats.


Glutathione homeostasis in human hepatic cells: overexpression of gamma-glutamylcysteine synthetase gene in cell lines resistant to buthionine sulfoximine, an inhibitor of glutathione synthesis.
The synthesis of glutathione (GSH) and its conjugation to xenobiotics are essential for detoxification in liver cells. To understand how cellular levels of GSH are balanced in response to environmental stress, we cloned two cell lines, HLE/BSO1-1 and HLE/BSO1-2, from human hepatic HLE/WT cells resistant to buthionine sulfoximine (BSO), an irreversible inhibitor of gamma-glutamylcysteine synthetase (GCS). HLE/BSO1-1 and HLE/BSO1-2 showed 35- and 40-fold higher resistance respectively, than the wild type to BSO. In the absence of BSO, cellular levels of GSH were 3.0-fold higher, whereas levels of Pi class glutathione thiol transferase, GSTP1, were 2-fold lower, in the subclones than in the wild type cells. GCS heavy subunit (GCSh) mRNA level were 2.5-fold higher in HLE/BSO1-1 and HLE/BSO1-2 as compared with HLE/WT. Sequences between -315 and -241 base pairs of the 5' region, which contain an AP1 site, were shown to be responsible for the enhanced expression of GCSh in HLE/BSO1-1 cells. The expression of a dominant-negative mutant of c-Jun was found to inhibit the AP1-dependent GCSh promoter activity in HLE/WT and HLE/BSO1-1. Both protein level of c-Jun and binding activity of AP-1 were increased in both HLE/BSO1-1 and HLE/BSO1-2 cells. The up-regulation of GCSh gene appeared to be due to enhanced GCSh promoter acting through AP-1 activation in BSO-resistant hepatic cells.


Multimodal physical activity recognition by fusing temporal and cepstral information.
A physical activity (PA) recognition algorithm for a wearable wireless sensor network using both ambulatory electrocardiogram (ECG) and accelerometer signals is proposed. First, in the time domain, the cardiac activity mean and the motion artifact noise of the ECG signal are modeled by a Hermite polynomial expansion and principal component analysis, respectively. A set of time domain accelerometer features is also extracted. A support vector machine (SVM) is employed for supervised classification using these time domain features. Second, motivated by their potential for handling convolutional noise, cepstral features extracted from ECG and accelerometer signals based on a frame level analysis are modeled using Gaussian mixture models (GMMs). Third, to reduce the dimension of the tri-axial accelerometer cepstral features which are concatenated and fused at the feature level, heteroscedastic linear discriminant analysis is performed. Finally, to improve the overall recognition performance, fusion of the multimodal (ECG and accelerometer) and multidomain (time domain SVM and cepstral domain GMM) subsystems at the score level is performed. The classification accuracy ranges from 79.3% to 97.3% for various testing scenarios and outperforms the state-of-the-art single accelerometer based PA recognition system by over 24% relative error reduction on our nine-category PA database.


Plant respiration: Controlled by photosynthesis or biomass?
Two simplifying hypotheses have been proposed for whole-plant respiration. One links respiration to photosynthesis; the other to biomass. Using a first-principles carbon balance model with a prescribed live woody biomass turnover, applied at a forest research site where multidecadal measurements are available for comparison, we show that if turnover is fast the accumulation of respiring biomass is low and respiration depends primarily on photosynthesis; while if turnover is slow the accumulation of respiring biomass is high and respiration depends primarily on biomass. But the first scenario is inconsistent with evidence for substantial carry-over of fixed carbon between years, while the second implies far too great an increase in respiration during stand development-leading to depleted carbohydrate reserves and an unrealistically high mortality risk. These two mutually incompatible hypotheses are thus both incorrect. Respiration is not linearly related either to photosynthesis or to biomass, but it is more strongly controlled by recent photosynthates (and reserve availability) than by total biomass.


Efficacy and tolerability of a new formulation of sodium phosphate tablets (INKP-101), and a reduced sodium phosphate dose, in colon cleansing: a single-center open-label pilot trial.
The tablet form of sodium phosphate for bowel preparation for colonoscopy contains microcrystalline cellulose. This inactive ingredient produces a residue that obscures mucosal visualization and is time-consuming to remove during colonoscopy. To perform an open-label study of efficacy and tolerability of a modified formulation with microcrystalline cellulose reduced by 50% (code named INKP-101) and a lower total dose of sodium phosphate. Patients scheduled for colonoscopy self-administered 28 INKP-101 tablets (42 g sodium phosphate). Colon cleansing efficacy was evaluated using a standard 4-point scoring system and the amount of microcrystalline cellulose present and time spent removing it using an 8-point scale. A total of 31 patients were screened and enrolled. Thirty patients had a colonoscopy and were evaluated for colon cleansing efficacy. Overall colon cleansing was rated as excellent and good in 90% and 10% of patients respectively. About 77% of patients had microcrystalline cellulose scores of 2 or 3 (corresponding to <1 or 1-2 min spent removing microcrystalline cellulose, respectively). The drug was well-tolerated and adverse events were generally benign. A new formulation of sodium phosphate with reduced microcrystalline cellulose and a lower total dose of sodium phosphate was effective for colonoscopy and well-tolerated.


Comparing mortality risk of patients with acute hip fractures admitted to a major trauma centre on a weekday or weekend.
Proximal femoral fractures are a major public health concern with estimated annual direct and social costs amounting to £2 billion and average 30-day mortality risk of 7.5%. In response to the recent debate over out-of-hours hospital provision we investigated the 'weekend effect' at a major trauma centre, caring for acute injuries. A single centre, multi-surgeon review of 2060 patients performed. The distribution of patient and treatment variables compared in patients admitted on a weekday or the weekend. Fewer patients met performance indicators during weekend admission, time to surgery (63 vs. 71%) and time to geriatric review (86 vs. 91%). Weekend admission 30-day mortality was marginally lower than weekday (9.7% vs. 10.2%, OR 0.94, 95% CI 0.67 to 1.32, p = 0.7383). Increasing age, female gender, co-morbidities and confusion increased mortality risk. Binary regression analysis including these variables found no significant 'weekend effect'. Despite the unit observing an increasing workload in the last five years, with meticulous workforce planning, senior doctor provisions and careful use of resources, it is possible to provide a seven-day fracture neck of femur service with no variation in thirty-day mortality by the day of admission.


Standardization of post-operative antimicrobials reduced exposure while maintaining good outcomes in pediatric liver transplant recipients.
Infections following orthotopic liver transplant (OLT) result in significant morbidity and mortality, warranting careful consideration of risks associated with antibiotic overuse and benefits of infection prevention. In the absence of specific guidelines for antimicrobial prophylaxis in pediatric OLT, we developed a standardized approach to post-operative (post-op) antimicrobial therapy including 48 hours of antibiotics, no vancomycin for post-op fever within the first 48 hours, and caspofungin only for certain situations. The goal was to reduce antimicrobial utilization and adverse outcomes associated with longer duration of and broader treatment while maintaining good outcomes. The impact of this standardization on antimicrobial utilization and clinical outcomes at the largest pediatric liver transplant center in the United States is described. All individuals receiving an OLT from 1/1/17-9/30/17 (N = 38) and 3/14/18-12/13/18 (N = 27) were included in the pre-intervention (PreI) and post-intervention (PostI) groups, respectively. The intervention resulted in a significant reduction in individuals receiving post-op broad-spectrum gram-negative antibiotics for >48 hours (76% PreI vs 44% PostI OLT recipients, P = .01) and post-op vancomycin use (50% PreI, vs 7.4% PostI, P < .001). There were no statistically significant differences between groups for post-op fever, positive pre-/post-operative cultures, receipt of massive transfusion, or hospital length of stay. In conclusion, following the implementation of a standardized approach to post-op prophylaxis, antimicrobial exposure was significantly reduced without affecting OLT recipient outcomes.


Nuclear factor kappaB dominant negative genetic constructs inhibit X-ray induction of cell adhesion molecules in the vascular endothelium.
X-ray-induced expression of inflammatory mediators has been proposed to contribute to radiation injury in normal tissues. Radiation-inducible inflammatory mediators include the cell adhesion molecule (CAM) E-selectin and the intercellular adhesion molecule (ICAM)-1. Nuclear factor (NF)kappaB is activated by X-rays and may participate in the transcriptional regulation of each of these inflammatory mediators. To determine whether NFkappaB inhibition abrogates X-ray induction of inflammatory mediators, we used two experimental approaches including NFkappaB inhibitory drugs and a dominant negative genetic construct. Human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells were treated with the NFkappaB inhibitors ALLN, PDTC, NAC, and MG132. After irradiation, E-selectin or ICAM-1 was measured by fluorescence-activated cell-sorting analysis. E-selectin and ICAM-1 expression was measured by use of immunofluorescence and fluorescence-activated cell-sorting analysis. E-selectin expression increased 7-fold, and ICAM-1 expression increased 4-fold after irradiation. All of the inhibitors attenuated E-selectin expression after irradiation. ALLN and MG132 attenuated radiation-induced ICAM expression. However, PDTC and NAC induced increased expression of ICAM-1 in HUVECs. Inhibition of X-ray induction of ICAM by these agents could not be demonstrated. In separate experiments, the NFkappaB dominant negative genetic construct was cotransfected with the promoter-reporter constructs by means of Lipofectin reagent. The ICAM promoter-reporter construct consists of the 1.2-kb segment of the human ICAM promoter upstream of the transcriptional start site linked to the luciferase reporter gene (pGL.FL-Luc). The E-selectin promoter-reporter construct consists of 525 bp upstream of the transcriptional start site of the human E-selectin promoter linked to the human growth hormone reporter gene (pE525-GH). Endothelial cells transfected with the ICAM-1 promoter-reporter construct showed a 3-fold induction after irradiation. Likewise, cells transfected with pE525-GH showed a 7-fold induction after irradiation. When cotransfected with the CAM reporter-promoter constructs, the NFkappaB dominant negative genetic construct abolished X-ray-induced transcriptional activation of the E-selectin and ICAM-1 promoters. NFkappaB inhibition is, therefore, a means of abrogating radiation-induced expression of CAMs.


A Bayesian approach to genetic association studies with family-based designs.
For genome-wide association studies with family-based designs, we propose a Bayesian approach. We show that standard transmission disequilibrium test and family-based association test statistics can naturally be implemented in a Bayesian framework, allowing flexible specification of the likelihood and prior odds. We construct a Bayes factor conditional on the offspring phenotype and parental genotype data and then use the data we conditioned on to inform the prior odds for each marker. In the construction of the prior odds, the evidence for association for each single marker is obtained at the population-level by estimating its genetic effect size by fitting the conditional mean model. Since such genetic effect size estimates are statistically independent of the effect size estimation within the families, the actual data set can inform the construction of the prior odds without any statistical penalty. In contrast to Bayesian approaches that have recently been proposed for genome-wide association studies, our approach does not require assumptions about the genetic effect size; this makes the proposed method entirely data-driven. The power of the approach was assessed through simulation. We then applied the approach to a genome-wide association scan to search for associations between single nucleotide polymorphisms and body mass index in the Childhood Asthma Management Program data.


Antioxidant supplementation for the treatment of acute lung injury: a meta-analysis.
This meta-analysis was performed to evaluate the evidence supporting antioxidant supplementation as an adjunct therapy to prevent oxidative damage and improve the clinical outcomes (mortality, length of hospital stay and duration of mechanical ventilation). The search strategy for randomized controlled trials (RCTs) involved the participation of two researchers who independently assessed the methodological quality of each full-text article that was available in the PubMed, ISI WEB of Knowledge and ScienceDirect databases. We extracted 110 studies from the past 10 years, but only 30 articles met the methodological criteria (RCT, blinded and statistically significant results), for a total of 241 animals and 256 patients. This study found an odds ratio (OR) of 0.45 [95% confidence interval (CI): 0.26 to 0.79] for death in the experimental group compared with placebo (six trials, n = 256), an OR of 0.46 [95% CI: 0.26 to 0.87] for hospitalization time and an OR of 0.63 [95% CI: 0.35 to 1.12] for mechanical ventilation time between groups. Conflicting evidence makes it impossible to recommend the routine use of antioxidant supplementation in critically ill patients.


Analysis of secondary pauses following termination of rapid atrial pacing in man.
The first ten cycles following cessation of atrial pacing were evaluated in 44 control subjects (mean age 52.9 +/- 14.88 yr) and 39 patients (mean age 62.9 +/- 15.41 yr) suspected of having sinus node dysfunction (SND). The maximal cycle length for each postpacing cycle following several pacing periods in each control subject was determined, and was normalized by dividing it by the subject's mean spontaneous control cycle length (SCL). Using the control group, a normalized maximal post-pacing response pattern (mean and SD) was derived. For each SND patient, a composite SD for each post-pacing cycle was calculated by adding the patient's SCL variance to the variance determined for each post-pacing cycle in the control group. Two composite SD above the mean value for each post-pacing cycle was selected as the upper limit of the normal recovery response and used to identify abnormal post-pacing responses in the 39 SND patients. Abnormally prolonged cycle lengths subsequent to the first escape cycle (secondary pauses) were found in 16/39 (41.0%) patients, of whom 11/39 (28.2%) had a prolonged SNRTmax. Of importance, 11/12 (91;7%) patients with documented SA block or sinus pauses prior to electrophysiologic study, demonstrated secondary pauses, while only 7/12 (58.3%) had a prolonged SNRTmax. Criteria are derived for the identification of secondary pauses during the postpacing period, and a close association between secondary pauses and the presence of spontaneous SA block or sinus pauses prior to electrophysiologic study is demonstrated.


Enhanced efficiency and air-stability of NiOX-based perovskite solar cells via PCBM electron transport layer modification with Triton X-100.
We modified phenyl-C61-butyric acid methyl ester (PCBM) for use as a stable, efficient electron transport layer (ETL) in inverted perovskite solar cells (PSCs). PCBM containing a surfactant Triton X-100 acts as the ETL and NiOX nanocrystals act as a hole transport layer (HTL). Atomic force microscopy and scanning electron microscopy images showed that surfactant-modified PCBM (s-PCBM) forms a high-quality, uniform, and dense ETL on the rough perovskite layer. This layer effectively blocks holes and reduces interfacial recombination. Steady-state photoluminescence and electrochemical impedance spectroscopy analyses confirmed that Triton X-100 improved the electron extraction performance of PCBM. When the s-PCBM ETL was used, the average power conversion efficiency increased from 10.76% to 15.68%. This improvement was primarily caused by the increases in the open-circuit voltage and fill factor. s-PCBM-based PSCs also showed good air-stability, retaining 83.8% of their initial performance after 800 h under ambient conditions.


On-chip, time-correlated, fluorescence lifetime extraction algorithms and error analysis.
A new, simple, and hardware-only fluorescence-lifetime-imaging microscopy (FLIM) is proposed to implement on-chip lifetime extractions, and their signal-to-noise-ratio based on statistics theory is also deduced. The results are compared with Monte Carlo simulations, giving good agreement. Compared with the commonly used iterative least-squares method or the maximum-likelihood-estimation- (MLE-) based, general purpose FLIM analysis software, our algorithm offers direct calculation of fluorescence lifetime based on the collected photon counts stored in on-chip counters and therefore delivers faster analysis for real-time applications, such as clinical diagnosis. Error analysis considering timing jitter based on statistics theory is carried out for the proposed algorithms and is also compared with MLE to obtain optimized channel width or measurement window and bit resolution of the time-to-digital converters for a given accuracy. A multi-exponential, pipelined fluorescence lifetime method based on the proposed algorithms is also introduced. The performance of the proposed methods has been tested on mono-exponential and four-exponential decay experimental data.


Characteristic of facial muscle and efferent nerve on physiology and anatomy.
To study the specialty of orbicularis oculi muscles, nerves and oris muscles, nerves and mechanism of difference of facial muscular injury in facial paralysis deeply. The conductive velocity of the efferent nerves of orbicularis oculi and oris muscles of the health human beings and guinea pigs is measured with electromyogram (EMG) apparatus. The conductive velocity of orbicularis oculi nerve is quicker and oris muscles are controlled by facial nerves on both sides. Measuring the threshold of Strength-Duration (S-D) curves of the motor point of orbicularis oculi and oris muscles shows the threshold of the former is lower. Measuring the diameter of orbicularis oculi and oris nerve fibers on the guinea pigs and rabbits shows the diameter of orbicularis oculi nerve fiber is bigger. The area of secondary synapse space of orbicularis oculi motor end plate is larger than that of oris under scanning electron microscope. Orbicularis oculi muscles, orbicularis oculi nerves and oris muscles, oris nerves all have their own characteristic on physiology and anatomy. It elucidated the mechanism that orbicularis oculi muscle is easy to be injured.


Chemical components and protective effects of Atractylodes japonica Koidz. ex Kitam against acetic acid-induced gastric ulcer in rats.
Atractylodes japonica Koidz. ex Kitam. (A. japonica, Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it's often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear. To investigate the protective effects of A. japonica on acetic acid-induced GU rats. The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms. 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1β, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways. These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.