Demonstration of URR-duplication variants of human papillomavirus type 6 in paraffin-embedded tissue sections of one condyloma acuminatum and one Buschke-Loewenstein tumour.
Human papillomavirus type 6 (HPV 6) induces condylomata acuminata and laryngeal papillomas. Occasionally, HPV 6 may also be found in low-grade verrucous carcinomas. In some tumours, genetic analysis revealed the presence of HPV 6 variants with rearrangements, mostly DNA duplications, within the upstream regulatory region (URR). In this study, we analysed 98 formalin-fixed, paraffin-embedded condylomata acuminata obtained from 54 patients for the presence of URR-duplication variants of HPV 6. HPV 6 DNA could be amplified by polymerase chain reaction (PCR) from 40 samples. One condyloma acuminatum contained a HPV 6 genome with rearranged URR. Analysis using restriction enzyme cleavage suggested a DNA duplication within the URR of approximately 200 bp, spanning the Hpa II site at nt 7863 and the Dde I site at nt 7843 but not involving the Rsa I site at nt 7633. In addition, we analysed the distribution of the already characterized URR-duplication variant HPV 6AC1B within different paraffin-embedded tissue sections of a Buschke-Loewenstein tumour. No correlation could be demonstrated between the presence of the rearranged genome and malignant histological changes. This result and the demonstration of an URR-duplication variant in a typical condyloma acuminatum suggest that duplications within the URR of HPV 6 are not directly related to malignant progression of HPV 6-induced tumours.


Detection and Quantification of Benzothiazoles in Exhaled Breath and Exhaled Breath Condensate by Real-Time Secondary Electrospray Ionization-High-Resolution Mass Spectrometry and Ultra-High Performance Liquid Chromatography.
2-Subtituted benzothiazoles are widely used industrial chemicals whose occurrence in environmental samples has been shown to be ubiquitous. However, knowledge about human exposure to these compounds and their excretion route is still scarce. Here, we demonstrate for the first time the detection of benzothiazole derivatives in exhaled breath. Real-time analysis of breath was carried out by means of secondary electrospray ionization coupled to high-resolution mass spectrometry. This coupling allowed not only the detection of these compounds in breath with a sensitivity in the pptv range but also their robust identification by comparing tandem high-resolution mass spectra from breath and standards. For further confirmation, benzothiazoles were also determined in exhaled breath condensate samples by means of ultra high-performance liquid chromatography. This approach strengthened the identification as a result of excellent matches in retention times and also allowed quantification. An estimated total daily exhalation of ca. 20 μg day(-1) was calculated for the six benzothiazole derivatives found in breath.


Role of First Metacarpal Osteotomy in the Management of Basilar Thumb Arthritis.
This study reviews outcomes of patients undergoing Wilson extension osteotomy of the first metacarpal for treatment of carpometacarpal (CMC) joint pain and deformity. The study reviews varied indications for Wilson osteotomy outlining technique and functional outcomes. Twelve patients (11 female, 1 male) with an average age at surgery of 50 (range, 25-67) underwent osteotomy during the study period. Diagnoses included seven patients with early degenerative changes of the CMC joint with painful subluxation or instability. The remaining patients had symptomatic adduction contracture in either end-stage arthritis (three) or following prior trapeziectomy (two). Average motion improved modestly among all groups with considerable improvement of metacarpophalangeal hyperextension in late deformity patients. Wilson osteotomy is a motion-preserving alternative procedure that may be indicated for patients with early CMC arthrosis and instability as well as for patients with adduction contractures in end-stage arthritis or posttrapeziectomy (Journal of Surgical Orthopaedic Advances 28(1):63-67, 2019).


Complexity of case mix in a regional allergy service.
Currently in the United Kingdom (UK), there is a mismatch between limited financial resources and the large proportion of patients with suspected allergies actually being referred to specialist allergy clinics. To better understand the case mix of patients being referred, we audited referrals to a regional allergy service over an 8 year period.The main source of data was consultant letters to General Practitioners (GP) summarising the diagnosis of patients, archived from January 2002 to September 2009. Letters were reviewed, extracting the clinic date, doctor seen, gender, date of birth, postcode, GP, and diagnoses. Diagnoses were classified into seven groups and illustrative cases for each group noted. Data from 2,028 new referrals with suspected allergy were analysed. The largest group of patients (43%) were diagnosed with a type I hypersensitivity. The other diagnostic groups were chronic idiopathic (spontaneous) urticaria (35%), suspected type I hypersensitivity but no allergen identified (8%), idiopathic (spontaneous) angioedema (8%), physical urticaria (2.5%), non-allergic symptoms (1.6%), type IV hypersensitivity (0.8%) and ACE inhibitor sensitivity (0.5%). Two thirds of patients seen were female with a higher percentage of female patients in the non type-I hypersensitivity group (71%) than the type 1 hypersensitivity (66%) (χ2 = 5.1, 1df, p = 0.024). The type 1 hypersensitivity patients were younger than other patients (38 Vs 46 years, t = -10.8, p < 0.001) This study highlights the complexity of specialist allergy practice and the large proportion of patients referred with non-type I hypersensitivities, chronic idiopathic (spontaneous) urticaria being by far the largest group. Such information is critical to inform commissioning decisions, define referral pathways and in primary care education.


Blockade of Her2/neu binding to Hsp90 by emodin azide methyl anthraquinone derivative induces proteasomal degradation of Her2/neu.
Overexpression of HER2/neu, a transmembrane tyrosine kinase acting as a coreceptor for other EGFR family members, is well-known to be associated with a poor prognosis in cancer. In the present study, we observed that emodin AMAD, a novel emodin azide methyl anthraquinone derivative, extracted from nature's giant knotweed rhizome of traditional Chinese herbs, potently decreased Her2/neu protein in dose- and time-dependent manners and also inhibited the downstream MAPK and PI3K-Akt signaling pathway. Intriguingly, reverse transcription-PCR and protein turnover assay revealed that the decrease of Her2/neu was independent of mRNA level but primarily owing to its protein stability. Meanwhile, proteasome inhibitor MG132 but not lysosome inhibitor chloroquine could restore Her2/neu and polyubiquitination of Her2/neu was augmented during emodin AMAD treatment. Furthermore, immunofluorescence study with anti-Her2/neu antibody showed that emodin AMAD disturbed the subcellular distribution of Her2/neu, with decreased location in the plasma membrane. Molecular docking studies predicted that AMAD can interact with the ATP-binding pocket of both Hsp90 and Her2/neu. Importantly, coimmunoprecipitation and immunofluorescence study revealed that emodin AMAD markedly impaired the binding between Hsp90 and Her2/neu and could bind to both Hsp90 and Her2/neu as reinforced by molecular modeling studies. In addition, combination of emodin AMAD treatment and siRNA against Her2 synergistically inhibited proliferation and induced apoptosis. Taken together, these data suggest that blockade of Her2/neu binding to Hsp90 and following proteasomal degradation of Her2/neu were involved in emodin AMAD-induced apoptosis in Her2/neu-overexpressing cancer cells. Our results provide suggestions that emodin AMAD could be promising as a new targeting therapeutic strategy in the treatment of Her2/neu-overexpressing cancers.


Polio outbreaks in Cameroon following the COVID-19 pandemic.
Polio is an infectious and disabling life-threatening disease caused by the poliovirus. This disease is prevented through vaccination. Though this viral infection has been eliminated in most parts of the world, a few countries are still endemic to wild poliovirus. In 2020, the World Health Organization (WHO) African Region, including Cameroon, was certified free of wild poliovirus. Some countries recurrently report circulating vaccine-derived poliovirus cases (cVDPV) despite recorded achievements. Also, the risk of importing poliovirus from endemic settings remains, particularly in the context of coronavirus disease (COVID-19). This study aimed to assess the state of polio in Cameroon and identify the situation during COVID-19. A data review was conducted from February to March 2023. Data on polio cases and vaccination coverage per region of Cameroon were reviewed from 2014 to 2022. Data were analyzed with Microsoft Excel, and the results were presented as proportions. The last wild poliovirus was reported in Cameroon in 2014, and the country benefitted from a response. No case of poliovirus was detected in the country from 2015 to 2018. After that, an increasing number of type two cVDPV were reported across 50% of the country's regions from 2019 to 2022. The outbreaks benefitted from responses with various oral polio vaccines, including the type two novel oral polio vaccine (nOPV-2). Though wild polioviruses have been eliminated in most countries, including Cameroon, cVDPV remains a significant problem. There is an urgent need to strengthen disease surveillance and vaccination to prevent cVDPV-2 in this country, particularly in the COVID-19 context.


Pediatric hypertension and hypertensive emergencies: recognition and management in the emergency department.
Pediatric hypertension is increasing in incidence, but remains greatly underrecognized, despite its severe long-term health consequences. Often discovered as incidental to another complaint, pediatric patients with hypertension may be asymptomatic but with markedly abnormal blood pressure, or they may have a true hypertensive emergency. This issue provides strategies to ensure that the child with asymptomatic hypertension receives appropriate screening and referrals, and outlines a systematic approach for the evaluation and treatment of the critically ill child who presents with symptoms of severe hypertension.


Electron probe x-ray microanalysis studies on the ionic environment of nuclei and the maintenance of chromatin structure.
We have demonstrated the application of electron probe X-ray microanalysis to studies aimed at determining the role of the ionic environment in the maintenance of a stable chromatin structure during interphase. Our results indicate that X-ray microanalysis can be used to accurately measure the concentration of ions, such as Na+ and K+ within subcellular compartments. We also present evidence from our X-ray microanalysis studies to show that only a portion of the K+ in the interphase nucleus is in a free ionic state and that the rest of the intranuclear K+ is adsorbed to intranuclear macromolecules. The stable structural state of interphase chromatin was correlated with the maintenance of a normal range in the chemical activities of monovalent ions in the oocyte nucleus. Finally, we demonstrated that the chemical activity of the monovalent ions probably increases beyond this normal interphase range as the chromatin in the nucleus condenses into discrete chromosomes during the first meiotic division in the amphibian oocyte. The above observations support the hypothesis of Kellermayer et al. (1984) that the maintenance of chromatin structure in the nucleus of living cells requires a balance between the presence or absence of mobile nuclear proteins and the chemical activity of monovalent cations. It also suggests that an elevation of the chemical activity of the monovalent cations above a normal range will result in the destabilization of interphase chromatin structure. It is hypothesized that an elevation of monovalent cations may be directly involved in the structural and functional changes in chromatin which are known to take place at the time of meiosis and mitosis.


Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm.
Inflammation plays a major role in the pathogenesis of several vascular pathologies, including abdominal aortic aneurysm (AAA). Evaluating the role of inflammation in AAA pathobiology and potentially outcome in vivo requires non-invasive tools for high-resolution imaging. We investigated the feasibility of X-ray computed tomography (CT) imaging of phagocytic activity using nanoparticle contrast agents to predict AAA outcome. Methods: Uptake of several nanoparticle CT contrast agents was evaluated in a macrophage cell line. The most promising agent, Exitron nano 12000, was further characterized in vitro and used for subsequent in vivo testing. AAA was induced in Apoe-/- mice through angiotensin II (Ang II) infusion for up to 4 weeks. Nanoparticle biodistribution and uptake in AAA were evaluated by CT imaging in Ang II-infused Apoe-/- mice. After imaging, the aortic tissue was harvested and used from morphometry, transmission electron microscopy and gene expression analysis. A group of Ang II-infused Apoe-/- mice underwent nanoparticle-enhanced CT imaging within the first week of Ang II infusion, and their survival and aortic external diameter were evaluated at 4 weeks to address the value of vessel wall CT enhancement in predicting AAA outcome. Results: Exitron nano 12000 showed specific uptake in macrophages in vitro. Nanoparticle accumulation was observed by CT imaging in tissues rich in mononuclear phagocytes. Aortic wall enhancement was detectable on delayed CT images following nanoparticle administration and correlated with vessel wall CD68 expression. Transmission electron microscopy ascertained the presence of nanoparticles in AAA adventitial macrophages. Nanoparticle-induced CT enhancement on images obtained within one week of AAA induction was predictive of AAA outcome at 4 weeks. Conclusions: By establishing the feasibility of CT-based molecular imaging of phagocytic activity in AAA, this study links the inflammatory signal on early time point images to AAA evolution. This readily available technology overcomes an important barrier to cross-sectional, longitudinal and outcome studies, not only in AAA, but also in other cardiovascular pathologies and facilitates the evaluation of modulatory interventions, and ultimately upon clinical translation, patient management.


Serum iron parameters in cirrhosis and chronic hepatitis: detailed description.
Serum iron parameters are affected by liver disorders. It is believed that the tests are unreliable in chronic liver disease, and systemic iron overload should be evaluated histologically in these patients. However, the effect of severity of chronic liver disease on serum iron parameters has not been evaluated. Similarly, differences between liver disease- and iron overload related iron parameter changes have not been clarified. We aimed to describe the effect of severity of chronic liver disease on serum iron tests and to elucidate the differences of liver disease- and iron overload-related iron parameter changes. Commonly used serum iron parameters were studied in patients with cirrhosis, chronic viral hepatitis and in persons with confirmed hemochromatosis. Cirrhosis cases were categorized according to Child-Pugh classification. We found that cirrhotic persons of any Child-Pugh class had deviations from normal results. Patients with chronic hepatitis had normal serum iron parameters. Total iron binding capacity decreased as liver disease progressed from hepatitis toward Class C cirrhosis (r= -0.53, p<0.001). Changes in ferritin and transferrin saturation were essentially opposite to this trend (r=0.3, p=0.01 and r=0.47, p<0.001, respectively). Serum iron level was lower in cirrhosis compared to hepatitis. Increased transferrin saturation and ferritin levels resembling iron overload were limited to Class C cirrhotics. Patients with true iron overload could be easily differentiated from these cases by hyperferremia. Aberrant serum iron test results indicate cirrhotic stage in chronic liver disease. Cirrhosis and systemic iron overload cause characteristically different changes in serum iron parameters.


Estimation of frequency factors for the calculation of kinetic isotope effects from classical and path integral free energy simulations.
We use the modified Bigeleisen-Mayer equation to compute kinetic isotope effect values for non-enzymatic phosphoryl transfer reactions from classical and path integral molecular dynamics umbrella sampling. The modified form of the Bigeleisen-Mayer equation consists of a ratio of imaginary mode vibrational frequencies and a contribution arising from the isotopic substitution's effect on the activation free energy, which can be computed from path integral simulation. In the present study, we describe a practical method for estimating the frequency ratio correction directly from umbrella sampling in a manner that does not require normal mode analysis of many geometry optimized structures. Instead, the method relates the frequency ratio to the change in the mass weighted coordinate representation of the minimum free energy path at the transition state induced by isotopic substitution. The method is applied to the calculation of 16/18O and 32/34S primary kinetic isotope effect values for six non-enzymatic phosphoryl transfer reactions. We demonstrate that the results are consistent with the analysis of geometry optimized transition state ensembles using the traditional Bigeleisen-Mayer equation. The method thus presents a new practical tool to enable facile calculation of kinetic isotope effect values for complex chemical reactions in the condensed phase.


Priming the Motor Cortex With Anodal Transcranial Direct Current Stimulation Affects the Acute Inhibitory Corticospinal Responses to Strength Training.
Frazer, AK, Howatson, G, Ahtiainen, JP, Avela, J, Rantalainen, T, and Kidgell, DJ. Priming the motor cortex with anodal transcranial direct current stimulation affects the acute inhibitory corticospinal responses to strength training. J Strength Cond Res 33(2): 307-317, 2019-Synaptic plasticity in the motor cortex (M1) is associated with strength training (ST) and can be modified by transcranial direct current stimulation (tDCS). The M1 responses to ST increase when anodal tDCS is applied during training due to gating. An additional approach to improve the M1 responses to ST, which has not been explored, is to use anodal tDCS to prime the M1 before a bout of ST. We examined the priming effects of anodal tDCS of M1 on the acute corticospinal responses to ST. In a randomized double-blinded cross-over design, changes in isometric strength, corticospinal excitability, and inhibition (assessed as area under the recruitment curve [AURC] using transcranial magnetic stimulation) were analyzed in 13 adults exposed to 20 minutes of anodal tDCS and sham tDCS followed by a ST session of the right elbow flexors. We observed a significant decrease in isometric elbow-flexor strength immediately after training (11-12%; p < 0.05), which was not different between anodal tDCS and sham tDCS. Transcranial magnetic stimulation revealed a 24% increase in AURC for corticospinal excitability after anodal tDCS and ST; this increase was not different between conditions. However, there was a 14% reduction in AURC for corticospinal inhibition when anodal tDCS was applied before ST when compared with sham tDCS and ST (all p < 0.05). Priming anodal tDCS had a limited effect in facilitating corticospinal excitability after an acute bout of ST. Interestingly, the interaction of anodal tDCS and ST seems to affect the excitability of intracortical inhibitory circuits of the M1 through nonhomeostatic mechanisms.


Prevalence and determinants of chronic kidney disease in women with hypertensive disorders in pregnancy in Nigeria: a cohort study.
Worldwide, hypertensive disorders in pregnancy (HDPs) complicate between 5 and 10% of pregnancies. Sub-Saharan Africa (SSA) is disproportionately affected by a high burden of HDPs and chronic kidney disease (CKD). Despite mounting evidence associating HDPs with the development of CKD, data from SSA are scarce. Women with HDPs (n = 410) and normotensive women (n = 78) were recruited at delivery and prospectively followed-up at 9 weeks, 6 months and 1 year postpartum. Serum creatinine was measured at all time points and the estimated glomerular filtration rates (eGFR) using CKD-Epidemiology equation determined. CKD was defined as decreased eGFR< 60 mL/min/1.73m2 lasting for ≥ 3 months. Prevalence of CKD at 6 months and 1 year after delivery was estimated. Logistic regression analyses were conducted to evaluate risk factors for CKD at 6 months and 1 year postpartum. Within 24 h of delivery, 9 weeks, and 6 months postpartum, women with HDPs were more likely to have a decreased eGFR compared to normotensive women (12, 5.7, 4.3% versus 0, 2 and 2.4%, respectively). The prevalence of CKD in HDPs at 6 months and 1 year postpartum was 6.1 and 7.6%, respectively, as opposed to zero prevalence in the normotensive women for the corresponding periods. Proportions of decreased eGFR varied with HDP sub-types and intervening postpartum time since delivery, with pre-eclampsia/eclampsia showing higher prevalence than chronic and gestational hypertension. Only maternal age was independently shown to be a risk factor for decreased eGFR at 6 months postpartum (aOR = 1.18/year; 95%CI 1.04-1.34). Prior HDP was associated with risk of future CKD, with prior HDPs being more likely to experience evidence of CKD over periods of postpartum follow-up. Routine screening of women following HDP-complicated pregnancies should be part of a postpartum monitoring program to identify women at higher risk. Future research should report on both the eGFR and total urinary albumin excretion to enable detection of women at risk of future deterioration of renal function.


Biogas production: evaluation of the influence of K2FeO4 pretreatment of maple leaves (Acer platanoides) on microbial consortia composition.
The potential of K2FeO4 as a pretreatment agent of a lignocellulosic material was examined on leaves of Acer platanodides as the sole substrate for biogas production by anaerobic digestion carried out through modelling laboratory-scaled semi-continuous reactors differing in loading rates and substrate (pretreated and untreated leaves). The quality of bioagas produced by K2FeO4-pretreated leaves was significantly better in terms of higher methane content and lower content of H2S. K2FeO4 had no crucial influence on growth inhibition of biogas-producing bacteria, which were analysed by comprehensive culture-independent methods utilising high-throughput sequencing of specific genes [bacterial and archaeal 16S rRNA, formyltetrahydrofolate synthetase gene (fhs), methyl-coenzyme M reductase α subunit gene (mcrA) and fungal internal transcribed spacers (ITS)]. The higher amount of CH4 in biogas utilising pretreated leaves as substrate could be caused by a shift to acetoclastic methanogenesis pathway, which was indicated by the higher amount of homoacetogenic bacteria and acetotrophic methanogens detected in those reactors.


Impact of occupational exposure on lead levels in women.
In 1994, 207 women participated in a study designed to examine the effects of occupational exposure and various lifestyle factors on bone and blood lead levels. In vivo measurements of Pb concentrations in tibia were performed by X-ray fluorescence. All 108 former smelter employees and 99 referents provided blood samples and answered a questionnaire on lifestyle characteristics and the relevant medical history. Lead concentrations in tibia and blood were significantly higher in the exposed group. The difference in mean bone Pb concentrations of the two groups is markedly greater than the difference in the mean blood Pb concentrations, supporting the view that bone Pb measurements are a more reliable determinant of Pb body burden. Chronic exposure did not result in any statistically significant differences in adverse pregnancy outcomes. A significantly lower age at the onset of menopause in occupationally exposed women may suggest that Pb causes adverse changes in the pattern of estrus and menses. The exposed women had lower bone Pb concentrations than those found in most studies on predominantly male workers. Blood Pb concentrations remain increased in women long after the cessation of occupational exposure, reflecting the importance of the endogenous exposure. The endogenous exposure relation found for postmenopausal exposed women is consistent with data on male smelter workers, whereas the relation found for premenopausal women is significantly lower. This suggests that sex plays an important role in the metabolism of lead, and current models of exposure extrapolated from male data may be inappropriate for use on women.


[Determination of 19 antibiotic and 2 sulfonamide metabolite residues in wild fish muscle in mariculture areas of Laizhou Bay using accelerated solvent extraction and high performance liquid chromatography-tandem mass spectrometry].
A sample preparation and analytical method with accelerated solvent extraction (ASE) and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS) was developed to detect 19 antibiotic (9 sulfonamides, 4 quinolones, 3 macrolides and 3 others) and 2 sulfonamide metabolite residues in fish muscle. The target compounds were extracted using ASE and purified simultaneously by a C18 resin in the extraction cell. The extracts were evaporated to dryness, and redissolved with the initial mobile phase for HPLC-MS/MS analysis after freezing centrifugation (10,000 r/min, -4 °C) to remove the fat and other matrix compounds further. The separation of the analytes was carried out on an Xterra MS C18 column with methanol-acetonitrile (1:1, v/v) as mobile phase A and 0. 1% formic acid (containing 0. 1% ammonium formate) as mobile phase B. The spiked recoveries of the method were 55. 2%-113. 3%, with the relative standard deviations of 0. 1% - 17. 6% (n = 6). The limits of detection ranged from 0. 003 to 0. 6 ng/g. The method was applied to two fish (Synechogobius hasta and Liza haematocheilus) collected in mariculture areas of Laizhou Bay and six antibiotics were detected, in which the mass concentrations of norfloxacin were highest with mean values of 67. 01 and 27. 58 ng/g, respectively. The method is simple, rapid, highly sensitive, and useful in the study on exposure levels and environmental behavior of the antibiotics.


Intraoperative 32P high-dose rate brachytherapy of the dura for recurrent primary and metastatic intracranial and spinal tumors.
Treatment of spinal and intracranial tumors with dural involvement is complicated by radiation tolerance of sensitive structures, especially in the setting of previous treatment. To evaluate whether intraoperative brachytherapy with short-range sources allows therapeutic dose delivery without damaging sensitive structures. The median doses of previous treatment were 3000 cGy (range, 1800-7200 cGy) for 8 patients with primary/recurrent and 17 patients with metastatic spinal tumors and 5040 cGy (range, 1300-6040 cGy) for 5 patients with locally recurrent and 2 patients with metastatic intracranial tumors. Patients underwent gross total or maximal resection of the tumor and were then treated with an intraoperative brachytherapy plaque consisting of a flexible silicone film incorporating P. A dose of 1000 cGy was delivered to a depth of 1 mm; the percent depth dose was less than 1% at 4 mm from the prescription depth. Median postoperative radiation doses of 2700 cGy (range, 1800-3000 cGy) were delivered to 15 spinal tumor patients and 3000 cGy (range, 1800-3000 cGy) to 3 intracranial tumor patients. The median follow-up was 4.4 months (range, 2.6-23.3 months) for spinal tumor patients and 5.3 months (range, 0.7-16.2) for intracranial tumor patients. At 6-month follow-up, for all spinal tumor patients, local progression-free survival and overall survival rates were both 83.3% (95% confidence interval [CI]: 62.3%-94.3%); for all intracranial tumor patients, the local progression-free survival rate was 62.5% (95% CI: 23.8%-90.9%) and the overall survival rate was 66.7% (95% CI: 26.7%-92.9%). There were no intraoperative or postoperative complications secondary to radiotherapy. Use of the P brachytherapy plaque is technically simple and not associated with increased risk of complications, even after multiple radiation courses. Local control rates were more than 80% in patients with proven radiation-resistant spinal disease.


Axial oblique MR imaging of the intrinsic ligaments of the wrist: initial experience.
To evaluate two separate MR sequences acquired in the axial oblique plane, parallel to the long axis of the scapholunate (SL) and lunotriquetral (LT) ligaments, to determine whether the addition of these sequences to the standard MR wrist examination improves visualization of the intrinsic ligaments, and the evaluation of their integrity. To our knowledge, this plane has not been described in the literature previously. In total we evaluated 26 patients with chronic wrist pain or instability, referred for MR imaging following assessment by an orthopedic surgeon or physiatrist. All patients underwent initial conventional tri-compartment wrist arthrography, which served as the reference standard. This was immediately followed by MR arthrography, in the standard coronal and true axial planes, as well as in the axial oblique plane. The SL and LT ligaments were initially assessed for the presence or absence of tear, using the standard coronal and true axial sequences, and subsequently re-evaluated with the addition of the axial oblique planes. A total of ten intrinsic ligament tears were identified with conventional arthrography: six SL and four LT tears. Five of the six SL tears were identified on the standard sequences. All six were diagnosed with the addition of the oblique sequences. There were three false-positive SL tears identified using standard MR imaging, and two false-positives with the addition of the oblique sequences. No LT tear was identified on standard sequences, whereas all four were confidently seen with the addition of oblique images. No false-positives of the LT ligament were recorded with either standard or axial oblique sequences. The study suggests that the addition of axial oblique MR sequences helps identify tears to the intrinsic ligaments of the wrist, particularly the LT ligament. In addition, the axial oblique images assist in localization of the tear.


Influential role of 7-Ketocholesterol in the progression of Alzheimer's disease.
Millions of people are affected by neurodegenerative diseases worldwide. They occur due to the loss of brain functions or peripheral nervous system dysfunction. If untreated, prolonged condition ultimately leads to death. Mostly they are associated with stress, altered cholesterol metabolism, inflammation and organelle dysfunction. Endogenous cholesterol and phospholipids in brain undergo auto-oxidation by enzymatic as well as non-enzymatic modes leading to the formation of by-products such as 4-hydroxynonenal and oxysterols. Among various oxysterols, 7-ketocholesterol (7KCh) is one of the major toxic components involved in altering neuronal lipid metabolism, contributing to inflammation and nerve cell damage. More evidently 7KCh is proven to induce oxidative stress and affects membrane permeability. Loss in mitochondrial membrane potential affects metabolism of cell organelles such as lysosomes and peroxisomes which are involved in lipid and protein homeostasis. This in turn could affect amyloidogenesis, tau protein phosphorylation and accumulation in pathological conditions of neurodegenerative diseases. Lipid alterations and the consequent pathogenic protein accumulation, results in the damage of cell organelles and microglial cells. This could be a reason behind disease progression and predominantly reported characteristics of neurodegenerative disorders such as Alzheimer's disease. This review focuses on the role of 7KCh mediated neurodegenerative Alzheimer's disease with emphasis on alterations in the lipid raft microdomain. In addition, current trends in the significant therapies related to 7KCh inhibition are highlighted.


Soft Tissue Esthetic Changes Following a Modified Twin Block Appliance Therapy: A Prospective Study.
Achieving a satisfactory facial esthetics is of utmost importance in the practice of orthodontics. Cl II div 1 patients often suffer from numerous adverse facial characteristics which may impair their social well-being. The objective of the current study was to evaluate the esthetic changes in such patients by using a modified twin block appliance. Seventy adolescent patients with mandibular deficiency consecutively underwent treatment with a modified twin block appliance for a mean period of 13 months. Soft tissue analyzes of Burstone and Mcnamara were applied to evaluate the changes before and after the treatment. The esthetic changes before and after the therapy were compared using parametric paired t tests analysis. p values less than 0.05 were considered significant. Facial convexity, lip incompetence, upper lip protrusion, and columellar inclination significantly decreased (p < 0.05) while Merrifield's Z-angle nasolabial angle, lower lip length, and mentolabial angle significantly increased (p < 0.05). Vertical facial height ratio, lower lip protrusion, upper lip length as well as nasal projection and inclination, did not change significantly (p > 0.05). Our findings indicated that a modified form of the twin block appliance can be substantially effective in the improvement of several aspects of patients' facial balance with minimum untoward effects. Adolescents suffering from mandibular deficiency can gain substantial facial balance with the twin block appliance. The whole face attractiveness, however, is another subject and should not be conflicted with the facial balance. Shahamfar M, Atashi MHA, Azima N. Soft Tissue Esthetic Changes Following a Modified Twin Block Appliance Therapy: A Prospective Study. Int J Clin Pediatr Dent 2020;13(3):255-260.


A Novel Translational Ovine Pulmonary Adenocarcinoma Model for Human Lung Cancer.
In vitro cell line and in vivo murine models have historically dominated pre-clinical cancer research. These models can be expensive and time consuming and lead to only a small percentage of anti-cancer drugs gaining a license for human use. Large animal models that reflect human disease have high translational value; these can be used to overcome current pre-clinical research limitations through the integration of drug development techniques with surgical procedures and anesthetic protocols, along with emerging fields such as implantable medical devices. Ovine pulmonary adenocarcinoma (OPA) is a naturally-occurring lung cancer that is caused by the jaagsiekte sheep retrovirus. The disease has similar histological classification and oncogenic pathway activation to that of human lung adenocarcinomas making it a valuable model for studying human lung cancer. Developing OPA models to include techniques used in the treatment of human lung cancer would enhance its translational potential, making it an excellent research tool in assessing cancer therapeutics. In this study we developed a novel OPA model to validate the ability of miniaturized implantable O2 and pH sensors to monitor the tumor microenvironment. Naturally-occurring pre-clinical OPA cases were obtained through an on-farm ultrasound screening programme. Sensors were implanted into OPA tumors of anesthetized sheep using a CT-guided trans-thoracic percutaneous implantation procedure. This study reports the findings from 9 sheep that received sensor implantations. Time taken from initial CT scans to the placement of a single sensor into an OPA tumor was 45 ± 5 min, with all implantations resulting in the successful delivery of sensors into tumors. Immediate post-implantation mild pneumothoraces occurred in 4 sheep, which was successfully managed in all cases. This is, to the best of our knowledge, the first description of the use of naturally-occurring OPA cases as a pre-clinical surgical model. Through the integration of techniques used in the treatment of human lung cancer patients, including ultrasound, general anesthesia, CT and surgery into the OPA model, we have demonstrated its translational potential. Although our research was tailored specifically for the implantation of sensors into lung tumors, we believe the model could also be developed for other pre-clinical applications.


Recombinant human angiostatin (rhAngiostatin) in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer: a phase II study from Indiana University.
Recombinant human angiostatin (rhAngiostatin) functions as a potent inhibitor of angiogenesis. This study combined rhAngiostatin with a standard chemotherapy regimen in patients with advanced non-small-cell lung cancer (NSCLC). Eligible patients had chemotherapy-naïve stage IIIB (with pleural effusion) or IV NSCLC, performance status (PS) 0 or 1, no history of bleeding, brain metastasis or requirements for anti-coagulation. Patients received carboplatin (AUC 5) intravenously and paclitaxel (175 mg/m2) intravenously day 1 + subcutaneous rhAngiostatin at either 15 mg or 60 mg twice daily. Cycles were repeated every 3 weeks, for up to six cycles. Patients without progression after completing at least four cycles were continued on maintenance rhAngiostatin until disease progression. Patient characteristics (n = 24) were: 16 males, median age 66 years (range 45-78), 54% PS 1, 83.3% stage IV and 62.5% adenocarcinoma. Grade 3/4 toxicities included: fatigue 47.8%, neutropenia 39.1%, dyspnea 39.1%, vascular 26.1% and infection 17.4%. The overall response rate was 39.1%, 39.1% stable disease and 21.7% progressive disease. Median time to progression was 144 days, and 1-year survival was 45.8%. rhAngiostatin in combination with paclitaxel and carboplatin is feasible and results in a high disease control rate in patients with advanced NSCLC.


The Chemical Route to a Carbon Dioxide Neutral World.
Excessive CO2 emissions in the atmosphere from anthropogenic activity can be divided into point sources and diffuse sources. The capture of CO2 from flue gases of large industrial installations and its conversion into fuels and chemicals with fast catalytic processes seems technically possible. Some emerging technologies are already being demonstrated on an industrial scale. Others are still being tested on a laboratory or pilot scale. These emerging chemical technologies can be implemented in a time window ranging from 5 to 20 years. The massive amounts of energy needed for capturing processes and the conversion of CO2 should come from low-carbon energy sources, such as tidal, geothermal, and nuclear energy, but also, mainly, from the sun. Synthetic methane gas that can be formed from CO2 and hydrogen gas is an attractive renewable energy carrier with an existing distribution system. Methanol offers advantages as a liquid fuel and is also a building block for the chemical industry. CO2 emissions from diffuse sources is a difficult problem to solve, particularly for CO2 emissions from road, water, and air transport, but steady progress in the development of technology for capturing CO2 from air is being made. It is impossible to ban carbon from the entire energy supply of mankind with the current technological knowledge, but a transition to a mixed carbon-hydrogen economy can reduce net CO2 emissions and ultimately lead to a CO2 -neutral world.


Evaluating maternity care using national administrative health datasets: how are statistics affected by the quality of data on method of delivery?
Information on maternity services is increasingly derived from national administrative health data. We evaluated how statistics on maternity care in England were affected by the completeness and consistency of data on "method of delivery" in a national dataset. Singleton deliveries occurring between April 2009 and March 2010 in English NHS trusts were extracted from the Hospital Episode Statistics (HES) database. In HES, method of delivery can be entered twice: 1) as a procedure code in core fields, and 2) in supplementary maternity fields. We examined overall consistency of these data sources at a national level and among individual trusts. The impact of different analysis rules for handling inconsistent data was then examined using three maternity statistics: emergency caesarean section (CS) rate; third/fourth degree tear rate amongst instrumental deliveries, and elective CS rate for breech presentation. We identified 629,049 singleton deliveries. Method of delivery was not entered as a procedure or in the supplementary fields in 0.8% and 12.5% of records, respectively. In 545,594 records containing both data items, method of delivery was coded consistently in 96.3% (kappa = 0.93; p < 0.001). Eleven of 136 NHS trusts had comparatively poor consistency (<92%) suggesting systematic data entry errors. The different analysis rules had a small effect on the statistics at a national level but the effect could be substantial for individual NHS trusts. The elective CS rate for breech was most sensitive to the chosen analysis rule. Organisational maternity statistics are sensitive to inconsistencies in data on method of delivery, and publications of quality indicators should describe how such data were handled. Overall, method of delivery is coded consistently in English administrative health data.


A Retrospective Evaluation of Subsurface Monopolar Radiofrequency for Lifting of the Face, Neck, and Jawline.
Subsurface monopolar radiofrequency (SMRF) has emerged as a new method for reducing skin laxity via the controlled delivery of thermal energy below the skin using a radiofrequency probe. To evaluate the overall efficacy of the treatment and satisfaction ratings of subjects who underwent a single SMRF treatment to the face, neck, or jawline (or some combination). A retrospective, single-center study was conducted in which data were obtained via subject follow-ups at 90 and 180 days posttreatment. A total of 35 subjects, 6 men and 29 women, underwent a single SMRF treatment. Overall, 77% of subjects reported improvement, and 64% reported satisfaction with the treatment site at Day 180 posttreatment. Subsurface monopolar radiofrequency represents an effective modality to achieve skin tightening of the face, neck, and jawline. The data suggest that there is an energy delivery threshold, above which a higher percentage of subjects report satisfaction. Analysis of treatments parameters suggests an optimal treatment time and tissue temperature that should be achieved to maximize results.


Mobilization and transplantation patterns of autologous hematopoietic stem cells in multiple myeloma and non-Hodgkin lymphoma.
The mobilization of hematopoietic stem cells can be a limiting factor for transplantation, yet little is known about how the availability of novel mobilizing agents has affected the practices of oncologists and transplant specialists. US-based oncologists (n = 48) and transplant specialists (n = 46) were separately surveyed with a partial overlap of assessed information. More transplant specialists than oncologists believed that the time between referral and first consultation is adequate (89.1% vs 54.2%; P < .001). The presence of comorbidities was the most common reason for patients not being referred for transplantation. Among oncologists, 31.3% avoided cyclophosphamide and 16.7% avoided lenalidomide to prevent mobilization impairment in patients with multiple myeloma (MM). Chemotherapy mobilization for MM was used by 23.9% of transplant specialists due to higher CD34+ yields and by 21.7% due to its anti-MM effect. In non-Hodgkin lymphoma (NHL), 26.1% of transplant specialists used chemotherapy mobilization due to higher CD34+ yields, and 26.1% collected hematopoietic stem cells on the rebound prior to chemotherapy. With regard to plerixafor use in MM, 36.9% of transplant specialists reported that they did not use it, and 28.3% said they reserved it for second mobilization. In NHL, 4.3% of transplant specialists reported not using plerixafor, and 39.1% reserved it for second mobilization. Educational needs were identified to promote adequate referral for transplantation as well as successful and cost-effective methods for the mobilization of hematopoietic stem cells.


An ab initio approach on the asymmetric stacking of GaAs 〈111〉 nanowires grown by a vapor-solid method.
This study provides an ab initio thermodynamics approach to take a step forward in the theoretical modeling on the growth of GaAs nanowires. In order to understand the effects of growth conditions on the involvement of stacking faults and polytypism, we investigated the vapor-phase growth kinetics under arbitrary temperature-pressure conditions by combining the atomic-scale calculation with the thermodynamic treatment of a vapor-solid system. Considering entropy contribution and electronic energy, the chemical potential and surface energies of various reconstructions were calculated as a function of temperature and pressure, leading to the prediction of the change in Gibbs free energy at each stage of nucleation and growth. This enabled us to predict the temperature-pressure-dependent variation in nucleation rate and formation probability of possible stacking sequences: zinc blende, stacking faults, twin, and wurtzite. As a result, the formation probabilities of stacking faults and polytypism were found to decrease with increasing temperature or decreasing pressure, which agreed well with available experiments. In addition, by showing that the formation probability of the stacking defects in GaAs nanowires grown along the 〈111〉B direction is about ten times higher than that along the 〈111〉A direction, the intriguing asymmetric stacking behavior during the growth along the polar direction and its dependence on growth conditions were fundamentally elucidated. The proposed ab initio approach bridges the gap between atomic-scale static calculation at zero-temperature and kinetic growth process under arbitrary vapor-phase conditions, and thus will contribute to the nanoscale growth not only for GaAs nanowires but also for other materials.


Effects of methylprednisolone, dantrolene, and their combination on experimental spinal cord injury.
This study aimed to evaluate the effect of methylprednisolone sodium succinate, dantrolene sodium, and their combination on experimental spinal cord injury. We used 25 rats (Rattus norvegicus) that were divided into five groups. The negative control group (NC) consisted of animals without spinal cord trauma. In the groups with spinal cord trauma, the positive control group (PC) was given no treatment, the MS group was treated with methylprednisolone, the MS/DS group was treated with methylprednisolone and dantrolene, and the DS group was treated with dantrolene alone. The animals' motor function was evaluated daily, as measured with the open field test. Eight days after surgery, the animals were euthanized for spinal cord collection. Descriptive morphological evaluation, anti-NeuN immunohistochemistry, TUNEL, and anti-Bax immunofluorescence were performed. There was no significant difference between the PC, MS, MS/DS and DS groups with respect to BBB scores, neuronal and glial staining, or Bax expression (P < 0.05). Therefore, we conclude that methylprednisolone sodium succinate, dantrolene sodium, or the combination of these drugs did not reduce neuronal and glial loss, intrinsic pathway apoptosis, or promote functional recovery.


Genome sequence, comparative analysis and haplotype structure of the domestic dog.
Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.


Endocrine control of uterine oxytocin receptors in the ewe.
Specific binding of [3H]oxytocin to high affinity sites (hormone receptors) in membrane preparations from uterine tissues of the ewe has been determined at varying stages of the oestrous cycle and in pregnancy. Mean receptor concentrations in caruncular and intercaruncular endometrium and in myometrium were 14.2, 1.9 and 13.0 fmol/mg protein respectively between days 10 and 13 of the cycle. By the day of oestrus these values had increased to 749, 1085 and 179 fmol/mg protein. These increases in receptor concentrations coincided with luteolysis and falling plasma progesterone levels and followed the preovulatory decline in peripheral oxytocin and rise in ovarian venous oestradiol-17 beta. Receptor concentrations were low in all uterine tissues from pregnant animals between days 14 and 19 after oestrus. Analysis of binding parameters by Scatchard plot suggested a single population of receptor molecules in each of the tissues studied with apparent dissociation constants in the range 1.9-2.2 nmol/l. A number of naturally occurring neurohypophysial peptides inhibited binding of [3H]oxytocin to the receptor from ewes at oestrus; the cross-reactions of arginine vasopressin and vasotocin exceeded that of oxytocin. Use of a receptor binding assay to measure oxytocin in extracts of corpora lutea on days 4 and 10 after oestrus gave values similar to those obtained by radioimmunoassay, suggesting the absence of other receptor-active peptides in the corpus luteum. It is concluded that the oxytocin receptor is present in both components of the endometrium, as well as in the myometrium and that changes in uterine receptor concentrations before oestrus are consistent with receptor activation by steroid hormones.


Seizure-induced Increased Neurogenesis Occurs in the Dentate Gyrus of Aged Sprague-Dawley Rats.
Neurogenesis in the hippocampal dentate gyrus persists throughout the lifespan of mammals, however, the rate of neurogenesis decreases as the animal ages. Although seizures increase neurogenesis in young adult brains, this relationship has not been shown in aged animals. Using doublecortin (DCX) immunocytochemistry, the number of DCX-labeled cells in the dentate gyrus from aged rats (23 months of age) was assessed 30 days following pilocarpine-induced seizures and was compared to the number obtained from age-matched control rats. DCX-labeled cells were located in the subgranular zone, at the border between the hilus and the granule cell layer, and within the granule cell layer in both epileptic and control aged brains. When comparing the aged epileptic rats to age-matched controls, there was a significant increase in the number of DCX-labeled cells that was almost four and a half-fold. Therefore, aged rats also display an increase in adult neurogenesis following seizures.


Nursing responsibilities in laser surgery.
The increasing use of lasers in surgery requires a knowledgeable surgical team. An essential member of this team is the nurse, who has specific responsibilities to ensure safety during laser use. In addition, the nurse must serve as the liaison between the medical staff, hospital administration, patient, and other personnel. Such a role requires that the nurse have an understanding of lasers, their clinical applications and surgical techniques, and most specifically their safe use.


Thromboxane as a measure of cutaneous vascular damage following irradiation.
The present study was designed to evaluate the role of thromboxane in radiation-induced cutaneous injury and to use the quantitation of cutaneous thromboxane B2 as an indicator of vascular alteration and tissue viability in canine skin. Ten adult intact male dogs underwent epithermal neutron irradiation with or without boron neutron capture. Skin biopsies were obtained from (1) within, (2) the edge of, and (3) outside the radiation field at 5, 8, 11, 14, 21, and 90 days after irradiation. Clinical changes at each sampling time were assigned a numerical score. One-half of each biopsy was assigned a numerical score based on histologic changes. Thromboxane B2 was measured from the second half by enzyme immunoabsorbent assay. Thromboxane B2 concentration paralleled the response of clinical and histologic score over time, indicating the value of thromboxane measurement for evaluation of skin changes secondary to irradiation.


Maternal and fetal effects of propofol anaesthesia in the pregnant ewe.
The objective of this study was to determine the effects of propofol (PRF) on maternal and fetal cardiopulmonary function during the last trimester of pregnancy. Six pregnant 2-3 year-old Ripollesa sheep, each weighing 78+/-8 kg were used in the study and prepared by placing catheters in the maternal jugular vein and carotid artery. A catheter was also placed in the fetal femoral artery. Twenty-four hours later the sheep were anaesthetized with PRF (6 mg/kg intravenous (IV) followed by a continuous infusion at a rate of 0.4 mg/kg/min for 60 min) and cardiopulmonary data collected. Further data were collected for 105 min following termination of the infusion. The maternal mean arterial pressure (MAP) and diastolic arterial pressure (DAP) were significantly decreased (P<0.05) during the first 15 min of the infusion period, while the maternal pH was also significantly decreased. Maternal PaCO(2) and PaO(2) were significantly increased throughout the total infusion period. It was further observed that the fetal pH decreased significantly, throughout the infusion period, whereas the fetal MAP, DAP and PaCO(2) were significantly increased during the first 15 min of the infusion, after which time all parameters returned to control values. No differences in either maternal or fetal parameters were observed between control and recovery times.


A multi-agent quantum Monte Carlo model for charge transport: Application to organic field-effect transistors.
We have developed a multi-agent quantum Monte Carlo model to describe the spatial dynamics of multiple majority charge carriers during conduction of electric current in the channel of organic field-effect transistors. The charge carriers are treated by a neglect of diatomic differential overlap Hamiltonian using a lattice of hydrogen-like basis functions. The local ionization energy and local electron affinity defined previously map the bulk structure of the transistor channel to external potentials for the simulations of electron- and hole-conduction, respectively. The model is designed without a specific charge-transport mechanism like hopping- or band-transport in mind and does not arbitrarily localize charge. An electrode model allows dynamic injection and depletion of charge carriers according to source-drain voltage. The field-effect is modeled by using the source-gate voltage in a Metropolis-like acceptance criterion. Although the current cannot be calculated because the simulations have no time axis, using the number of Monte Carlo moves as pseudo-time gives results that resemble experimental I/V curves.


Cardiovascular Responses during Head-Down Crooked Kneeling Position Assumed in Muslim Prayers.
Movement dysfunction may be expressed in terms of symptoms experienced in non-physiological postures, and head-down crooked kneeling (HDCK) is a posture frequently assumed by Muslims during prayer activities. The purpose of this study was to investigate the cardiovascular responses in the HDCK posture. Seventy healthy volunteers, comprising 35 males and 35 females, participated in the study. Cardiovascular parameters of blood pressure and pulse rate of the participants were measured in rested sitting position and then at one and three minutes into the HDCK posture. Two-way ANOVA was used to determine the differences between cardiovascular responses at rest and in the HDCK posture, and the Student t test was utilized to determine gender difference in cardiovascular responses at rest and at one and three minutes into the HDCK posture. The study showed a significant decrease in systolic and diastolic blood pressures at one minute into the HDCK posture and an increase in pulse rate at one and three minutes into the HDCK posture, as compared to the resting values. Rate pressure product also rose at one minute into the HDCK posture, whereas pulse pressure increased at one and three minutes into the HDCK posture, as compared with the resting values. However, no significant change was observed in the mean arterial pressure values. The findings from this study suggest that no adverse cardiovascular event can be expected to occur for the normal duration of this posture during Muslim prayer activities.


Evaluation of Surfactants on Graphene Dispersion and Thermal Performance for Heat Dissipation Coating.
With the development of thin and high-power electronic devices, heat dissipation has become an important and urgent issue in thermal management. In this study, a water-based epoxy was used as a polymer matrix to prepare heat dissipation coatings utilizing low volatile organic compounds, which were environmentally friendly and had a high heat-dissipating performance. Graphene flakes, multi-walled carbon nanotubes and aluminum oxide particles were used as fillers for preparing the heat dissipation coating. The graphene flakes and multi-walled carbon nanotubes were dispersed in a water-based epoxy by adding sodium dihexyl sulfosuccinate and poly (dimethyldiallylammonium chloride). These two surfactants were combined as a dispersant to improve the dispersibility of the carbon nanomaterials in the water-based epoxy. The synergistic effect of the well-dispersed fillers improved the heat-dissipating performance. The experimental results show that the infrared emissivity of the heat dissipation film was 0.96 after filling 30 wt% aluminum oxide particles, 2 wt% graphene flakes and 2 wt% multi-walled carbon nanotubes into a water-based epoxy. The heat dissipation film reduced the thermal equilibrium temperature of the bare copper panel by 17.8 °C under a heating power of 10 W. The film was applied in a heat dissipation test on a 15 W LED bulb, and the thermal equilibrium temperature was reduced by 21.3 °C. The results demonstrate that the carbon nanomaterial-based heat dissipation coating with a water-based epoxy could significantly reduce the thermal equilibrium temperature, giving a high potential for the application of thermal management.


A major asymmetric dust trap in a transition disk.
The statistics of discovered exoplanets suggest that planets form efficiently. However, there are fundamental unsolved problems, such as excessive inward drift of particles in protoplanetary disks during planet formation. Recent theories invoke dust traps to overcome this problem. We report the detection of a dust trap in the disk around the star Oph IRS 48 using observations from the Atacama Large Millimeter/submillimeter Array (ALMA). The 0.44-millimeter-wavelength continuum map shows high-contrast crescent-shaped emission on one side of the star, originating from millimeter-sized grains, whereas both the mid-infrared image (micrometer-sized dust) and the gas traced by the carbon monoxide 6-5 rotational line suggest rings centered on the star. The difference in distribution of big grains versus small grains/gas can be modeled with a vortex-shaped dust trap triggered by a companion.


Occurrence of pharmaceuticals and UV filters in swimming pools and spas.
The occurrence of 32 pharmaceuticals and 14 UV filters in swimming pools and spas was studied. Fifty-one water samples were collected from 17 pools located in sport centres and hotels in Catalonia, Spain. The samples were analysed by liquid chromatography-tandem mass spectrometry. The pharmaceuticals atenolol, carbamazepine, hydrochlorothiazide, metronidazole, ofloxacin, sulfamethoxazole, acetaminophen, ibuprofen, ketoprofen and phenazone were measured in water samples at concentrations higher than their limit of quantification (LOQ). The highest concentration of any individual pharmaceutical was measured for the diuretic hydrochlorothiazide (904 ng/L). The most frequently detected pharmaceutical was carbamazepine, as it was observed in more than half of all the water samples measured (53 %, 27/51). The UV filters at concentrations higher than LOQ in water samples were BP1, BP2, BP3, BP8, THB, 4DHB, 4MBC, OD-PABA, 1HBT, MeBT and DMeBT. The highest concentration of UV filter observed was 4MBC (69.3 ng/L) while the most frequent UV filters in the samples were 1HBT (59 %, 30/51). The results also showed that pharmaceuticals and UV filters were most frequently found in spas. Finally, from a water treatment technology perspective, the lowest occurrence of pharmaceuticals was in the pools applying sand filters followed by disinfection by sodium hypochlorite, while the lowest occurrence of UV filters was in the pools applying coagulation, sand filtration, UV and salt electrolysis.


Critical Care Society of Southern Africa adult patient blood management guidelines: 2019 Round-table meeting, CCSSA Congress, Durban, 2018.
The CCSSA PBM Guidelines have been developed to improve patient blood management in critically ill patients in southern Africa. These consensus recommendations are based on a rigorous process by experts in the field of critical care who are also practicing in South Africa (SA). The process comprised a Delphi process, a round-table meeting (at the CCSSA National Congress, Durban, 2018), and a review of the best available evidence and international guidelines. The guidelines focus on the broader principles of patient blood management and incorporate transfusion medicine (transfusion guidelines), management of anaemia, optimisation of coagulopathy, and administrative and ethical considerations. There are a mix of low-middle and high-income healthcare structures within southern Africa. Blood products are, however, provided by the same not-for-profit non-governmental organisations to both private and public sectors. There are several challenges related to patient blood management in SA due most notably to a high incidence of anaemia, a frequent shortage of blood products, a small donor population, and a healthcare system under financial strain. The rational and equitable use of blood products is important to ensure best care for as many critically ill patients as possible. The summary of the recommendations provides key practice points for the day-to-day management of critically ill patients. A more detailed description of the evidence used to make these recommendations follows in the full clinical guidelines section.


In vivo activation of naive CD4+ T cells in nasal mucosa-associated lymphoid tissue following intranasal immunization with recombinant Streptococcus gordonii.
The antigen-specific primary activation of CD4+ T cells was studied in vivo by adoptive transfer of ovalbumin-specific transgenic T cells (KJ1-26+ CD4+) following intranasal immunization with recombinant Streptococcus gordonii. A strain of S. gordonii expressing on its surface a model vaccine antigen fused to the ovalbumin (OVA) peptide from position 323 to 339 was constructed and used to study the OVA-specific T-cell activation in nasal mucosa-associated lymphoid tissue (NALT), lymph nodes, and spleens of mice immunized by the intranasal route. The recombinant strain, but not the wild type, activated the OVA-specific CD4+ T-cell population in the NALT (89% of KJ1-26+ CD4+ T cells) just 3 days following immunization. In the cervical lymph nodes and in the spleen, the percentage of proliferating cells was initially low, but it reached the peak of activation at day 5 (90%). This antigen-specific clonal expansion of KJ1-26+ CD4+ T cells after intranasal immunization was obtained with live and inactivated recombinant bacteria, and it indicates that the NALT is the site of antigen-specific T-cell priming.


Prediction of resting metabolic rate in critically ill adult patients: results of a systematic review of the evidence.
Metabolic rate is generally assessed by use of equations in critically ill patients, but evidence pertaining to the validity of these equations in this population has not been systematically evaluated. This paper represents the first such systematic analysis in adult patients. A work group created by the American Dietetic Association identified pertinent peer-reviewed articles. The work group systematically evaluated these articles and formulated conclusion statements and grades based on the available evidence. Seven equations plus the Fick method were found to have validation work that met criteria for inclusion in this analysis. The Harris-Benedict equation with and without modifiers had the most validation work behind it (n=13), followed by Ireton-Jones (1992 and 1997) (n=9), Penn State (1998, 2003) (n=2), and Swinamer (n=1). Five studies pertaining to the Fick method met acceptance criteria. Based on these validation studies, the Harris-Benedict, Ireton-Jones 1997, and Fick methods can be confidently eliminated from use in assessment of energy expenditure in critically ill patients. The Penn State 2003, Swinamer, and Ireton-Jones 1992 equations may be useful in critically ill nonobese patients, whereas the Ireton-Jones 1992 and Penn State 1998 equations seem to be useful in obese patients. The strength of these conclusions is moderated because of limited and sometimes inconsistent data. More validation work is needed to confirm and increase the strength of these conclusions.


Prestimulus EEG Power Predicts Conscious Awareness But Not Objective Visual Performance.
Prestimulus oscillatory neural activity has been linked to perceptual outcomes during performance of psychophysical detection and discrimination tasks. Specifically, the power and phase of low frequency oscillations have been found to predict whether an upcoming weak visual target will be detected or not. However, the mechanisms by which baseline oscillatory activity influences perception remain unclear. Recent studies suggest that the frequently reported negative relationship between α power and stimulus detection may be explained by changes in detection criterion (i.e., increased target present responses regardless of whether the target was present/absent) driven by the state of neural excitability, rather than changes in visual sensitivity (i.e., more veridical percepts). Here, we recorded EEG while human participants performed a luminance discrimination task on perithreshold stimuli in combination with single-trial ratings of perceptual awareness. Our aim was to investigate whether the power and/or phase of prestimulus oscillatory activity predict discrimination accuracy and/or perceptual awareness on a trial-by-trial basis. Prestimulus power (3-28 Hz) was inversely related to perceptual awareness ratings (i.e., higher ratings in states of low prestimulus power/high excitability) but did not predict discrimination accuracy. In contrast, prestimulus oscillatory phase did not predict awareness ratings or accuracy in any frequency band. These results provide evidence that prestimulus α power influences the level of subjective awareness of threshold visual stimuli but does not influence visual sensitivity when a decision has to be made regarding stimulus features. Hence, we find a clear dissociation between the influence of ongoing neural activity on conscious awareness and objective performance.


Burkholderia pseudomallei: in vitro susceptibility to some new and old antimicrobials.
The treatment of melioidosis currently involves the use of antimicrobials such as ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline. Evaluation of other antimicrobials with activity against the organism continues to be pursued, however, as the causative organism, B. pseudomallei, may not always be susceptible to the above antimicrobials. This study aimed to test the susceptibility of Malaysian isolates of B. pseudomallei against imipenem, meropenem, ertapenem, moxifloxacin and azithromycin. 80 previously stocked clinical isolates collected between 1978 and 2003 from the UMMC, Kuala Lumpur were tested for in vitro susceptibility to these antimicrobials using the E-test minimum inhibitory concentration method. 100% of isolates were sensitive to imipenem and meropenem, 97.5% were sensitive to trimethoprim-sulfamethozaxole, 37.5% to moxifloxacin, and only a minority was sensitive to ertapenem (7.5%). Using breakpoints for Staphylococcus and Haemophilus, 5.0%-6.3% of isolates were sensitive to azithromycin. In conclusion, our findings support the in vitro efficacy of imipenem, meropenem and trimethoprim-sulfamethoxazole against B. pseudomallei. Moxifloxacin, ertapenem and azithromycin cannot be recommended for the treatment of melioidosis; however, further studies are needed to test the efficacy of azithromycin in combination with quinolones.


Autotrophic Growth of Gas Vacuolate Strains of Microcyclus aquaticus on Methanol and Hydrogen.
Seven strains of Microcyclus aquaticus were found to be capable of growth on methanol and hydrogen as energy sources. Carbon was incorporated as CO(2) via the Calvin cycle, as shown by the presence of ribulosebisphosphate carboxylase activity in methanol-grown cells and by the absence of key enzymes of the ribulose monophosphate and serine pathways. In addition, incoporation of [C]methanol into cells was diminished when cultures were incubated in gas atmospheres enriched with carbon dioxide.


Is vaginal breech delivery associated with higher risk for perinatal death and cerebral palsy compared with vaginal cephalic birth? Registry-based cohort study in Norway.
This paper aims to study if vaginal breech delivery is associated with increased risk for neonatal mortality (NNM) or cerebral palsy (CP) in Norway where vaginal delivery accounts for 1/3 of all breech deliveries. Cohort study using information from the national Medical BirthRegister and Cerebral Palsy Register. Births in Norway 1999-2009. 520 047 term-born singletons without congenital malformations. NNM, CP and a composite outcome of these and death during birth. Compared with cephalic births, breech births had substantially increased risk for NNM but not for CP. Vaginal delivery was planned for 7917 of 16 700 fetuses in breech, while 5561 actually delivered vaginally. Among these, NNM was 0.9 per 1000 compared with 0.3 per 1000 in vaginal cephalic delivery, and 0.8 per 1000 in those actually born by caesarean delivery (CD) in breech. Compared with planned cephalic delivery, planned vaginal delivery was associated with excess risk for NNM (OR 2.4; 95% CI 1.2 to 4.9), while the OR associated with planned breech CD was 1.6 (95% CI 0.7 to 3.7). These risks were attenuated when NNM was substituted by the composite outcome. Vaginal breech delivery was not associated with excess risk for CP compared with vaginal cephalic delivery. Vaginal breech delivery, regardless of whether planned or actual, and actual breech CD were associated with excess risk for NNM compared with vaginal cephalic delivery, but not with CP. The risk for NNM and CP in planned breech CD did not differ significantly from planned vaginal cephalic delivery. However, the absolute risk for these outcomes was low, and taking into consideration potential long-term adverse consequences of CD for the child and later deliveries, we therefore conclude that vaginal breech delivery may be recommended, provided competent obstetric care and strict criteria for selection to vaginal delivery.


Nutritional, clinical and socioeconomic profile of patients with cystic fibrosis treated at a referral center in northeastern Brazil.
To describe the profile of patients with cystic fibrosis (CF). A prospective, cross-sectional study involving CF patients < 18 years of age, evaluated between March and July of 2006 at a referral center in northeastern Brazil. Nutritional assessment was performed using Z scores for height/age (H/A), weight/age (W/A) and weight/height (W/H), as well as %weight/height (%W/H) and body composition measurements. Socioeconomic and clinical data were obtained. Twenty-one patients were evaluated, 12 (57.1%) of whom were female. Mean age at diagnosis was 3.8 +/- 3.9 years. The principal features at diagnosis were respiratory infection (85.7%), steatorrhea (66.7%) and nutritional deficit (47.6%). The mean Z scores for W/A, H/A and W/H were 0.73 +/- 0.28, 0.34 +/- 0.21 and 0.73 +/- 0.35, respectively. Mean %W/H was 94.52 +/- 1.58. The percentage of malnourished children assessed by Z score differed from that assessed by %W/H (nutritional deficit in 66.7% and 33.3%, respectively; p > 0.05). Socioeconomic status, clinical status and Shwachman score were better among well-nourished patients than among those classified as malnourished (p < 0.05 for Shwachman score). Normal nutritional status was identified based on nutritional indicators (W/A, H/A and W/H), whereas nutritional deficit was identified by assessing body composition. Socioeconomic factors proved favorable, especially maternal education and per capita income. Age at diagnosis was higher than that reported in the literature, although the Shwachman score and the incidence of respiratory infections demonstrated that the patients presented good clinical status.


Acanthopanax senticosus polysaccharide suppressing proliferation and metastasis of the human non-small cell lung cancer NCI-H520 cells is associated with Wnt/β-catenin signaling.
Lung cancer (LC) is the highest lethality in all tumors. Non-small cell lung cancer (NSCLC) accounts for about 80% of all LC. Acanthopanax senticosus polysaccharide (ASPS) is extracted from the root of Acanthopanax senticosus (AS). Herein, we examined the effect and molecular mechanism of ASPS on NSCLC. The proliferation, invasion and migration of NCI-H520 cells were detected by cell counting kit-8 (CCK-8), transwell assay and wound healing assay, respectively. The epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway-related factors were evaluated using quantitative real-time PCR (QRT-PCR) and western blot assay. Our results observed that ASPS significantly decreased the proliferation of cells at 24 and 48 h. Moreover, ASPS markedly repressed the invasion and migration capacities of cells in a concentration-dependent manner. Besides, ASPS obviously down-regulated the levels of matrix metalloproteinase-2 (MMP-2), MMP-9, fibronectin 1 (FN1), vimentin, wnt3a, phosphorylated-glycogen synthase kinase 3β (p-GSK3β) and cyclin D1, whereas, up-regulating E-cadherin level. The level of GSK3β was not changed in the different groups. ASPS conspicuously inhibited the abilities of proliferation and metastasis in human non-small cell lung cancer cell line NCI-H520 possibly by suppressing Wnt/β-catenin pathway mediated-EMT.


Methylation of miR-155-3p in mantle cell lymphoma and other non-Hodgkin's lymphomas.
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma (NHL). In cancers, tumor suppressive microRNAs may be silenced by DNA hypermethylation. By microRNA profiling of representative EBV-negative MCL cell lines before and after demethylation treatment, miR-155-3p was found significantly restored. Methylation-specific PCR, verified by pyrosequencing, showed complete methylation of miR-155-3p in one MCL cell line (REC-1). 5-aza-2'-deoxycytidine treatment of REC-1 led to demethylation and re-expression of miR-155-3p. Over-expression of miR-155-3p led to increased sub-G1 apoptotic cells and reduced cellular viability, demonstrating its tumor suppressive properties. By luciferase assay, lymphotoxin-beta (LT-β) was validated as a miR-155-3p target. In 31 primary MCL, miR-155-3p was found hypermethylated in 6(19%) cases. To test if methylation of miR-155-3p was MCL-specific, miR-155-3p methylation was tested in an additional 191 B-cell, T-cell and NK-cell NHLs, yielding miR-155-3p methylation in 66(34.6%) including 36(27%) non-MCL B-cell, 24(53%) T-cell and 6(46%) of NK-cell lymphoma. Moreover, in 72 primary NHL samples with RNA, miR-155-3p methylation correlated with miR-155-3p downregulation (p=0.024), and LT-β upregulation (p=0.043). Collectively, miR-155-3p is a potential tumor suppressive microRNA hypermethylated in MCL and other NHL subtypes. As miR-155-3p targets LT-β, which is an upstream activator of the non-canonical NF-kB signaling, miR-155-3p methylation is potentially important in lymphomagenesis.


Family environment, expressed emotion and adolescent self-harm: a review of conceptual, empirical, cross-cultural and clinical perspectives.
Self-harm in young people is a complex and pervasive problem with a number of co-existing risk factors. Although research has implicated a range of family variables in understanding the onset, maintenance and prevention of adolescent self-harm, relatively little attention has been given to the expressed emotion (EE) construct. Based on a narrative review and synthesis of peer-reviewed literature up to and including 2011, this paper considers the conceptual background and empirical evidence for the role of family environment in the expression of adolescent self-harm, with a particular focus on EE. The clinical implications of this literature for working with young people and families from different cultures are also addressed. In summary, the surveyed research provides insufficient evidence for a direct causal link between family environment and adolescent self-harm, with questions raised about the temporal sequencing of measured variables, specificity of implicated family risk factors, and the nature and role of protective factors in families. Emerging evidence for an association between high EE and adolescent self-harm requires replication in well-controlled, prospective studies. There is also a lack of empirically-supported, family-based treatment modalities for adolescents who self-harm. Intervention strategies should be guided by personalised formulation, taking into account individual vulnerabilities, strengths and social contexts, as well as cultural norms for family environment.


From particle self-assembly to functionalized sub-micron protein patterns.
Biologically relevant nanopatterns are useful platforms to address fundamental questions, for example, regarding protein-protein and cell-protein interactions. For the creation of nanopatterns, complex and expensive instrumentation is often needed. We present a simple but versatile patterning method using a combination of particle and subsequent molecular self-assembly to produce ordered structures in the micron and sub-micron range. Polystyrene particles were, in a first step, assembled via dip-coating or dried in a drying cell. Silicon wafers and glass slides coated with SiO(2) and a top layer of 11 nm of TiO(2) were used as substrates. Large hexagonally ordered particle monolayers were formed with high reproducibility. These were subsequently shrunk in a controlled manner by exposure to a O(2)/N(2) plasma and subsequently used as etching masks to transfer the particle pattern onto the substrate, creating TiO(2) features in an SiO(2) background. After removing the mask the oxide contrast was translated in three simple dip-and-rinse steps into a biochemical contrast of protein-coated features in an inert background. In short, alkane phosphates were first selectively adsorbed to the TiO(2) features. Then the SiO(2) background was backfilled using poly(L-lysine)-graft-poly(ethylene glycol) and finally streptavidin was adsorbed to the hydrophobic alkane phosphate SAMs, allowing subsequent binding and hybridization of biotinylated DNA.


Nonefficacy of routine removal of CSF during neurodiagnostic procedures.
The charts of 750 patients were reviewed to determine the value of routinely removing cerebrospinal fluid at the time of myelography and cisternography for chemical and cytologic examination. In most patients cerebrospinal fluid findings were normal. In the few abnormal studies, the findings were often uninformative, superfluous, or insufficient for appropriate diagnosis. In no instance did routine analysis of cerebrospinal fluid uncover occult disease. Routine removal of cerebrospinal fluid for analysis in radiologic spinal taps seems to be inappropriate, and removal should be dictated by the clinical context in which the procedure is performed.


The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial.
Twenty-two patients with distal diabetic polyneuropathy confirmed both clinically and by objective nerve function studies, completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid on their neuropathy. Patients received either 360 mg gamma-linolenic acid (12 patients) or indistinguishable placebo capsules (10 patients) for 6 months. All patients were assessed at the beginning and end of the study period by neuropathy symptom and sign scoring, motor and sensory nerve conduction studies, and thermal threshold measurements. When compared with the placebo group, patients on gamma-linolenic acid showed statistically significant improvement in neuropathy symptom scores (p less than 0.001), median nerve motor conduction velocity (p less than 0.01) and compound muscle action potential amplitude (p less than 0.01), peroneal nerve motor conduction velocity (p less than 0.05) and compound muscle action potential amplitude (p less than 0.05), median (p less than 0.01) and sural (p less than 0.001) sensory nerve action potential amplitude and ankle heat threshold (p less than 0.001) and cold threshold (p less than 0.01) values. gamma-Linolenic acid therapy might have a useful role in the prevention and treatment of distal diabetic polyneuropathy.


Frequency of mutant T lymphocytes defective in the expression of the T-cell antigen receptor gene among radiation-exposed people.
The frequency of mutant T lymphocytes defective in T-cell receptor gene (alpha or beta) expression was measured using the 2-color flow cytometric technique. Results for a total of 203 atomic bomb survivors, 78 of whom were proximally exposed (DS86 doses of greater than or equal to 1.5 Gy) and 125 of whom were distally exposed (DS86 dose of less than 0.005 Gy), showed that the mutant frequency was significantly higher in males than in females. No significant dose effects were observed. In contrast, a significant increase of mutant frequency was observed for 6 patients treated with Thorotrast, a contrast medium containing thorium-232 formerly used for radioligands. In addition, thyroid disease patients treated with 131I showed a dose-related increase of mutant frequency. It was suggested that the present T-cell receptor mutation assay has a unique characteristic as a biological dosimeter for measurement of recent exposures to genotoxic agents.


Comparison of laparoscopic and open nephrectomy for adult polycystic kidney disease: operative challenges and technique.
Autosomal dominant polycystic kidney disease an inherited systemic disorder is characterized by the development of multiple cysts in the kidneys and other organs. When nephrectomy is indicated, the laparoscopic approach is challenging due to the massive size of these kidneys. We present our technique and evaluate the surgical outcomes of laparoscopic versus open nephrectomy for patients with such condition. A retrospective review was done for six laparoscopic and six open nephrectomies performed by two laparoscopic surgeons in two university hospitals between January 2004 and December 2004. Preoperative, intraoperative, and postoperative data are presented. A standard subcostal incision was used for the open cases while for the laparoscopic approach a 3-4-port transperitoneal laparoscopic approach was used to dissect the involved kidney, which is then removed intact or morcellated through pfannenstiel, midline, or expanded port site incision. The laparoscopic patients had a longer operative time with one major complication compared to the open group. On the other hand laparoscopic group achieved minimal blood loss, less narcotic requirement and a shorter hospital stay. No conversion to open required in the laparoscopy group. At a median follow up of 1 year no long-term complications reported in either groups. Laparoscopic nephrectomy for polycystic kidney disease is a feasible and safe alternative to open approach. In addition to low morbidity, other advantages of laparoscopic surgery also achieved in this subset of patients such as the ability to remove the dissected kidney through a small incision, reduced postoperative pain, short hospital stay, and excellent cosmesis.


Colocalization of hyperpolarization-activated, cyclic nucleotide-gated channel subunits in rat retinal ganglion cells.
The current-passing pore of mammalian hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels is formed by subunit isoforms denoted HCN1-4. In various brain areas, antibodies directed against multiple isoforms bind to single neurons, and the current (I(h)) passed during hyperpolarizations differs from that of heterologously expressed homomeric channels. By contrast, retinal rod, cone, and bipolar cells appear to use homomeric HCN channels. Here, we assess the generality of this pattern by examining HCN1 and HCN4 immunoreactivity in rat retinal ganglion cells, measuring I(h) in dissociated cells, and testing whether HCN1 and HCN4 proteins coimmunoprecipitate. Nearly half of the ganglion cells in whole-mounted retinae bound antibodies against both isoforms. Consistent with colocalization and physical association, 8-bromo-cAMP shifted the voltage sensitivity of I(h) less than that of HCN4 channels and more than that of HCN1 channels, and HCN1 coimmunoprecipitated with HCN4 from membrane fraction proteins. Finally, the immunopositive somata ranged in diameter from the smallest to the largest in rat retina, the dendrites of immunopositive cells arborized at various levels of the inner plexiform layer and over fields of different diameters, and I(h) activated with similar kinetics and proportions of fast and slow components in small, medium, and large somata. These results show that different HCN subunits colocalize in single retinal ganglion cells, identify a subunit that can reconcile native I(h) properties with the previously reported presence of HCN4 in these cells, and indicate that I(h) is biophysically similar in morphologically diverse retinal ganglion cells and differs from I(h) in rods, cones, and bipolar cells.


THE PRODUCTION OF PURE ABSOLUTE ALCOHOL WITH CALCIUM CARBIDE AND ANHYDROUS COPPER SULPHATE.
(1) The above is recommended as an economical, convenient and quick method for producing absolute alcohol on a laboratory scale. If the distillation is executed with free flame, excessive or careless heating must be avoided near the end of the operation because of the copper acetylide in the residue. (2) Calcium carbide is recommended over potassium permanganate or anhydrous copper sulphate as a qualitative reagent in detecting traces of water in alcohol.


Daily temperature fluctuations unpredictably influence developmental rate and morphology at a critical early larval stage in a frog.
Environmental temperature has profound consequences for early amphibian development and many field and laboratory studies have examined this. Most laboratory studies that have characterized the influence of temperature on development in amphibians have failed to incorporate the realities of diel temperature fluctuations (DTF), which can be considerable for pond-breeding amphibians. We evaluated the effects of different ecologically relevant ranges of DTF compared with effects of constant temperatures on development of embryos and larvae of the Korean fire-bellied toad (Bombina orientalis). We constructed thermal reaction norms for developmental stage, snout-vent length, and tail length by fitting a Gompertz-Gaussian function to measurements taken from embryos after 66 hours of development in 12 different constant temperature environments between 14°C and 36°C. We used these reaction norms as null models to test the hypothesis that developmental effects of DTF are more than the sum of average constant temperature effects over the distribution of temperatures experienced. We predicted from these models that growth and differentiation would be positively correlated with average temperature at low levels of DTF but not at higher levels of DTF. We tested our prediction in the laboratory by rearing B. orientalis embryos at three average temperatures (20°C, 24°C, and 28°C) and four levels of thermal variation (0°C, 6°C, 13°C, and 20°C). Several of the observed responses to DTF were significantly different from both predictions of the model and from responses in constant temperature treatments at the same average temperatures. At an average temperature of 24°C, only the highest level of DTF affected differentiation and growth rates, but at both cooler and warmer average temperatures, moderate DTF was enough to slow developmental and tail growth rates. These results demonstrate that both the magnitude of DTF range and thermal averages need to be considered simultaneously when parsing the effects of changing thermal environments on complex developmental responses, particularly when they have potential functional and adaptive significance.


18F-FDG PET imaging of myocardial viability in an experienced center with access to 18F-FDG and integration with clinical management teams: the Ottawa-FIVE substudy of the PARR 2 trial.
(18)F-FDG PET may assist decision making in ischemic cardiomyopathy. The PET and Recovery Following Revascularization (PARR 2) trial demonstrated a trend toward beneficial outcomes with PET-assisted management. The substudy of PARR 2 that we call Ottawa-FIVE, described here, was a post hoc analysis to determine the benefit of PET in a center with experience, ready access to (18)F-FDG, and integration with clinical teams. Included were patients with left ventricular dysfunction and suspected coronary artery disease being considered for revascularization. The patients had been randomized in PARR 2 to PET-assisted management (group 1) or standard care (group 2) and had been enrolled in Ottawa after August 1, 2002 (the date that on-site (18)F-FDG was initiated) (n = 111). The primary outcome was the composite endpoint of cardiac death, myocardial infarction, or cardiac rehospitalization within 1 y. Data were compared with the rest of PARR 2 (PET-assisted management [group 3] or standard care [group 4]). In the Ottawa-FIVE subgroup of PARR 2, the cumulative proportion of patients experiencing the composite event was 19% (group 1), versus 41% (group 2). Multivariable Cox proportional hazards regression showed a benefit for the PET-assisted strategy (hazard ratio, 0.34; 95% confidence interval, 0.16-0.72; P = 0.005). Compared with other patients in PARR 2, Ottawa-FIVE patients had a lower ejection fraction (25% +/- 7% vs. 27% +/- 8%, P = 0.04), were more often female (24% vs. 13%, P = 0.006), tended to be older (64 +/- 10 y vs. 62 +/- 10 y, P = 0.07), and had less previous coronary artery bypass grafting (13% vs. 21%, P = 0.07). For patients in the rest of PARR 2, there was no significant difference in events between groups 3 and 4. The observed effect of (18)F-FDG PET-assisted management in the 4 groups in the context of adjusted survival curves demonstrated a significant interaction (P = 0.016). Comparisons of the 2 arms in Ottawa-FIVE to the 2 arms in the rest of PARR 2 demonstrated a trend toward significance (standard care, P = 0.145; PET-assisted management, P = 0.057). In this post hoc group analysis, a significant reduction in cardiac events was observed in patients with (18)F-FDG PET-assisted management, compared with patients who received standard care. The results suggest that outcome may be benefited using (18)F-FDG PET in an experienced center with ready access to (18)F-FDG and integration with imaging, heart failure, and revascularization teams.


Minimising added classification error using Walsh coefficients.
Two-class supervised learning in the context of a classifier ensemble may be formulated as learning an incompletely specified Boolean function, and the associated Walsh coefficients can be estimated without the knowledge of the unspecified patterns. Using an extended version of the Tumer-Ghosh model, the relationship between added classification error and second-order Walsh coefficients is established. In this brief, the ensemble is composed of multilayer perceptron base classifiers, with the number of hidden nodes and epochs systematically varied. Experiments demonstrate that the mean second-order coefficients peak at the same number of training epochs as ensemble test error reaches a minimum.


Steep, cheap and deep: an ideotype to optimize water and N acquisition by maize root systems.
A hypothetical ideotype is presented to optimize water and N acquisition by maize root systems. The overall premise is that soil resource acquisition is optimized by the coincidence of root foraging and resource availability in time and space. Since water and nitrate enter deeper soil strata over time and are initially depleted in surface soil strata, root systems with rapid exploitation of deep soil would optimize water and N capture in most maize production environments. • THE IDEOTYPE: Specific phenes that may contribute to rooting depth in maize include (a) a large diameter primary root with few but long laterals and tolerance of cold soil temperatures, (b) many seminal roots with shallow growth angles, small diameter, many laterals, and long root hairs, or as an alternative, an intermediate number of seminal roots with steep growth angles, large diameter, and few laterals coupled with abundant lateral branching of the initial crown roots, (c) an intermediate number of crown roots with steep growth angles, and few but long laterals, (d) one whorl of brace roots of high occupancy, having a growth angle that is slightly shallower than the growth angle for crown roots, with few but long laterals, (e) low cortical respiratory burden created by abundant cortical aerenchyma, large cortical cell size, an optimal number of cells per cortical file, and accelerated cortical senescence, (f) unresponsiveness of lateral branching to localized resource availability, and (g) low K(m) and high Vmax for nitrate uptake. Some elements of this ideotype have experimental support, others are hypothetical. Despite differences in N distribution between low-input and commercial maize production, this ideotype is applicable to low-input systems because of the importance of deep rooting for water acquisition. Many features of this ideotype are relevant to other cereal root systems and more generally to root systems of dicotyledonous crops.


Novel agents for the treatment of pancreatic adenocarcinoma. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.
There are urgent needs to develop novel and more effective regimens to improve outcomes of pancreatic cancer given its dismal prognosis and limited treatment options. Several phase I clinical trials involving novel agents were recently presented at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting. It appears that hedgehog inhibition with IPI-926 was well-tolerated and might be effective in treating pancreatic cancer when combined with gemcitabine. The survival benefits will be tested in the following randomized phase II trial. The new combination of gemcitabine and blockade of checkpoint kinases with AZD7762 showed an acceptable safety profile. Furthermore, inhibition of PI3K by BAY80-6946 was well tolerated with PET-CT suggesting reduction in FDG uptake in some pancreatic cancer. The benefits of above novel agents/regimens need to be further tested in phase II trials.


Melt electrospinning of poly(ε-caprolactone) scaffolds: phenomenological observations associated with collection and direct writing.
Melt electrospinning and its additive manufacturing analogue, melt electrospinning writing (MEW), are two processes which can produce porous materials for applications where solvent toxicity and accumulation in solution electrospinning are problematic. This study explores the melt electrospinning of poly(ε-caprolactone) (PCL) scaffolds, specifically for applications in tissue engineering. The research described here aims to inform researchers interested in melt electrospinning about technical aspects of the process. This includes rapid fiber characterization using glass microscope slides, allowing influential processing parameters on fiber morphology to be assessed, as well as observed fiber collection phenomena on different collector substrates. The distribution and alignment of melt electrospun PCL fibers can be controlled to a certain degree using patterned collectors to create large numbers of scaffolds with shaped macroporous architectures. However, the buildup of residual charge in the collected fibers limits the achievable thickness of the porous template through such scaffolds. One challenge identified for MEW is the ability to control charge buildup so that fibers can be placed accurately in close proximity, and in many centimeter heights. The scale and size of scaffolds produced using MEW, however, indicate that this emerging process will fill a technological niche in biofabrication.