A Novel Technique for Detecting Depressive Disorder: A Speech Database-Based Approach.
Depression is the second most diagnosed disease in the world and is predicted to be the highest by the year 2030. Depressive disorder impacts both on mentally and physically, thus diagnosing this disorder in early stage is essential. Automatic Depression Detection (ADD) system via speech can greatly facilitate early-stage depression diagnosis. Development of such systems demands a standard balanced database. In this work, we present a novel labeled audio distress interview database. To our knowledge, this is the first depression database in Bengali language that contains audio responses from depressed and non-depressed subjects. Alongside this, we present a set of hand-crafted acoustic features that effectively detect depression mood using speech signals. Finally, we justify the quality of our developed database and the efficacy of the feature set in predicting depression using a baseline machine learning (ML) model. We believe that the annotated database will be a valuable resource for use by treating clinicians.Clinical Relevance-This research reports a new speech database in Bengali language for depression detection. This database can be used in healthcare by developing an automatic prediction model for depression detection.


Myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are hematopoietic neoplasms characterized by an ineffective hematopoiesis associated with cytopenia(s), functional abnormalities of bone marrow lineages, morphologic dysplasia, and a progression to acute myeloid leukemia. The pathogenesis of MDS is exceedingly complex and involves the hematopoietic stem cells/hematopoietic precursors, bone marrow microenvironment, and complex interaction between these components. The diagnostic strategy in MDS has evolved significantly over the years from a strategy based almost exclusively on peripheral blood smear and bone marrow aspirate morphology to the integrated approach used in the 2001 and 2008 World Health Organization (WHO) classification schemes. In parallel with the diagnostic approach, evolution has occurred in the prognostic assessment and evaluation of treatment response. The prognostic assessment now includes both disease-related factors and patient-specific characteristics such as nonhematologic comorbidities. All these developments are particularly important considering the ever-increasing treatment options available for MDS. This review focuses on the diagnostic approach to MDS and highlights recent developments in the pathogenesis as well as select clinical advances. We present the overview of the minimal diagnostic criteria for a diagnosis of MDS, the WHO classification scheme, and briefly address the risk stratification.


Secretion of active subtilisin YaB by a simultaneous expression of separate pre-pro and pre-mature polypeptides in Bacillus subtilis.
Alkaline elastase YaB, produced by alkalophilic Bacillus YaB, is an extracellular serine protease having 55% homology to subtilisin BPN' and thus could be called subtilisin YaB. It is synthesized as a 378-amino acid preproenzyme and secreted into the culture medium as a 265-amino acid mature protease. To examine if the pro-peptide of subtilisin YaB functions in trans to guide the folding of secreted subtilisin YaB in vivo, we made genes encoding the pre-pro, pro and pre-mature portions and placed them under the control of the spac-1 promoter on a multi-copy plasmid. When simultaneous expression in Bacillus subtilis of both the pre-pro and pre-mature genes was induced with 0.5 mM isopropyl-1-thio-beta-D-galactopyranoside (IPTG), protease activity was detected in the medium. On the other hand, we could not detect protease activity when the expression of either the pre-mature gene alone or both the pro and pre-mature genes was induced. From these results, we concluded that the pro region functions in trans and outside the cells for the proper folding and activation of the enzyme.


The efficiency-equity trade-off, self-interest, and moral principles in health and safety valuation.
Policy makers try to take account of public preferences when making trade-offs between policy options. Yet most estimates of the value of health and safety reflect only individuals' self-interested preferences, neglecting their preferences over the distribution of public resources. We conduct an experiment in which participants choose between policy options that differ in their efficiency (expected number of fatalities or cases of ill health they would prevent) and their equity (defined in terms of the balance of risk reductions for different sections of the population). The policy options were framed as interventions to improve a hypothetical city's water supply that would reduce the risk of death or ill health for people in different areas of the city to varying degrees. In order to examine whether self-interest would affect the trade-offs, we asked half of the sample about scenarios where they would personally benefit from some options. Our results suggest that efficiency is the most important single factor determining preferences between policy options, but decisions were influenced almost as much by equity as by efficiency. The effect of self-interest was smaller than that of the general concern for efficiency. We also elicited participants' stated moral principles regarding trade-offs between equity, efficiency and self-interest, and found that their expressed principles were well-aligned with their choices. Our findings contribute to the growing evidence that distributional concerns matter when evaluating health interventions.


Synthetic genetic circuits to uncover the OCT4 trajectories of successful reprogramming of human fibroblasts.
Reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs) is inefficient, with heterogeneity among transcription factor (TF) trajectories driving divergent cell states. Nevertheless, the impact of TF dynamics on reprogramming efficiency remains uncharted. We develop a system that accurately reports OCT4 protein levels in live cells and use it to reveal the trajectories of OCT4 in successful reprogramming. Our system comprises a synthetic genetic circuit that leverages noise to generate a wide range of OCT4 trajectories and a microRNA targeting endogenous OCT4 to set total cellular OCT4 protein levels. By fusing OCT4 to a fluorescent protein, we are able to track OCT4 trajectories with clonal resolution via live-cell imaging. We discover that a supraphysiological, stable OCT4 level is required, but not sufficient, for efficient iPSC colony formation. Our synthetic genetic circuit design and high-throughput live-imaging pipeline are generalizable for investigating TF dynamics for other cell fate programming applications.


Paternity analysis of wild-caught females shows that sperm package size and placement influence fertilization success in the bushcricket Pholidoptera griseoaptera.
In species where females store sperm, males may try to influence paternity by the strategic placement of sperm within the female's sperm storage organ. Sperm may be mixed or layered in storage organs, and this can influence sperm use beyond a 'fair raffle'. In some insects, sperm from different matings is packaged into discrete packets (spermatodoses), which retain their integrity in the female's sperm storage organ (spermatheca), but little is known about how these may influence patterns of sperm use under natural mating conditions in wild populations. We examined the effect of the size and position of spermatodoses within the spermatheca and number of competing ejaculates on sperm use in female dark bushcrickets (Pholidoptera griseoaptera) that had mated under unmanipulated field conditions. Females were collected near the end of the mating season, and seven hypervariable microsatellite loci were used to assign paternity of eggs laid in the laboratory. Females contained a median of three spermatodoses (range 1-6), and only six of the 36 females contained more than one spermatodose of the same genotype. Both the size and relative placement of the spermatodoses within the spermatheca had a significant effect on paternity, with a bias against smaller spermatodoses and those further from the single entrance/exit of the spermatheca. A higher number of competing males reduced the chances of siring offspring for each male. Hence, both spermatodose size and relative placement in the spermatheca influence paternity success.


A common 844INS68 insertion variant in the cystathionine beta-synthase gene.
Mildly elevated plasma homocysteine has been shown to be associated with an elevated risk for cardiovascular disease. In this study, we analyzed the frequency of a common 844ins68 insertion variant in the cystathionine beta-synthase gene (CBS) in patients with arterial occlusive disease and in controls and assessed the association between the insertion variant and plasma homocysteine concentrations. The insertion variant was equally distributed between both study groups. Furthermore, the presence of this insertion variant, either in the heterozygous or the homozygous state, is not associated with hyperhomocysteinemia. We therefore conclude that this common 844ins68 variant is a neutral insertion variant.


Importance of Urinary Drug Screening in the Multiple Sleep Latency Test and Maintenance of Wakefulness Test.
Multiple sleep latency testing (MSLT) and the maintenance of wakefulness test (MWT) are gold-standard objective tests of daytime sleepiness and alertness; however, there is marked variability in their interpretation and practice. This study aimed to determine the incidence of positive drug screens and their influence on MSLT, MWT, and polysomnographic variables. All patients attending Eastern Health Sleep Laboratory for MSLT or MWT over a 21-mo period were included in the study. Urinary drug screening for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates was performed following overnight polysomnography (PSG). Demographics and PSG variables were compared. Of 69 studies, MSLT (43) and MWT (26), 16% of patients had positive urinary drug screening (7 MSLT; 4 MWT). Drugs detected included amphetamines, cannabinoids, opiates, and benzodiazepines. No patient self-reported use of these medications prior to testing. No demographic, MSLT or MWT PSG data or overnight PSG data showed any statistical differences between positive and negative drug screen groups. Of seven MSLT patients testing positive for drug use, one met criteria for the diagnosis of narcolepsy and five for idiopathic hypersomnia. On MWT, three of the four drug-positive patients had a history of a motor vehicle accident and two patients were occupational drivers. These findings indicate drug use is present in patients attending for daytime testing of objective sleepiness and wakefulness. These data support routine urinary drug screening in all patients undergoing MSLT or MWT studies to ensure accurate interpretation in the context of illicit and prescription drug use.


The effects of dual blockade of the renin-angiotensin system on urinary protein and transforming growth factor-beta excretion in 2 groups of patients with IgA and diabetic nephropathy.
The therapeutic benefits of dual blockade of the renin-angiotensin system (RAS) have been inconsistent on renal function and proteinuria. To know the contribution of the heterogeneity of study subjects to such inconsistency, we evaluated the effects of dual blockade of RAS in 2 groups of selected renal diseases, IgA and diabetic nephropathy. To avoid confounding by the blood pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added on the patients with long-term, optimally controlled blood pressure taking ACE inhibitors. Twenty-four-hour urinary protein excretion rate and urinary TGF-beta1 level were measured as surrogate markers of renal injury. We conducted a prospective crossover trial with 14 IgA and 18 type-2-diabetic nephropathy patients showing moderate degree of proteinuria (> or = 1.0 g/day) and renal dysfunction (creatinine clearance 25 - 75/ml/min). Four to 8 mg once-daily dose of candesartan and placebo were alternatively added on ramipril dose of 5 - 7.5 mg/day for 16 weeks. All baseline data except for the age factor were statistically the same between the 2 disease groups. Twenty-four-hour mean arterial blood pressures were 91.2 +/- 1.6 and 92.3 +/- 1.8 mmHg in IgA and diabetic nephropathy patients respectively at baseline (p = NS). Mean arterial pressure did not change by the addition of candesartan or placebo in both groups. The addition of candesartan (combination) reduced 24-hour urinary protein excretion rate in IgA nephropathy patients with a mean change of -12.3 +/- 4.5%, which is significantly greater compared to a mean change of -0.1 +/- 3.3% after the addition of placebo (placebo) (mean difference 12.4 +/- 5.0, 95% CI 1.2 - 23.5; p < 0.05). Urinary TGF-beta1 level was reduced considerably by the combination therapy, with a -28.9 +/- 6.0% decrease, which was significantly different to that by the placebo, with +4.3 +/- 12.4% (33.3 +/- 13.5, 3.2 - 63.3; p < 0.05). In diabetic nephropathy patients, the addition of candesartan did not reduce 24-hour urinary protein excretion rate. Mean changes of 24-hour urinary protein excretion rate were -0.8 +/- 4.7% by the combination therapy and +0.5 +/- 6.1% by placebo (mean difference 1.3 +/- 4.7, 95% CI -6.8 - 13.5; p < NS). The level of urinary TGF-beta1 was reduced by the combination therapy, with -14.3 +/- 9.5% decrease, but it did not reach statistical significance compared to placebo of +0.7 +/- 15.5% (15.0 +/- 13.5, -14.4 - 44.5; p < NS). The changes in 24-hour urinary protein excretion rate and urinary TGF-beta1 level were neither correlated with each other, nor with the change in mean arterial pressure. Significant changes in the renal function were not detected during the study period. Definite beneficial effects of dual blockade of RAS on proteinuria and TGF-beta1 excretion were found in IgA nephropathy patients, which was independent of blood pressure-reducing effect. With our 16-week trial, such benefits were not observed in type 2 diabetic nephropathy. The reduction in urinary TGF-beta1 level suggests that the combination therapy may provide additional renoprotection through the antisclerosing effects. Based on our results, for a proper interpretation the therapeutic effects of the combination therapy should be evaluated separately according to the underlying renal disease.


Previous H1N1 influenza A viruses circulating in the Mongolian population.
Four influenza A viruses of the subtype H1N1, isolated from Mongolian patients in Ulaanbaatar between 1985 and 1991, were analysed by sequencing of various RNA segments. The isolate from 1985 was found to be highly related in all genes sequenced to strains isolated from camels in the same region and at about the same time. These camel isolates were presumably derived from a UV-light inactivated reassortant vaccine (PR8 x USSR/77) prepared in Leningrad in 1978 and used in the Mongolian population at that time [19]. The human isolate from 1988 was also found to be a derivative of a reassortant between PR8 and USSR/77; in contrast to the 1985 isolate, however, it contained an HA closely related to PR8. One of the Mongolian isolates from 1991 (111/91) was in all genes sequenced closely related to PR8, while the other isolate from 1991 (162/91) was closely related to H1N1 strains isolated around 1986 in other parts of the world. About 12% of 235 convalescent sera collected in various parts of Mongolia contained antibodies against PR8, while none of German control sera contained such antibodies. The mutational and evolutionary rates of the Mongolian strains seem to be significantly lower when compared to the rates of human influenza A strains isolated in other parts of the world. This might indicate that these rates depend to a certain extent on the population density. Thus, viruses from remote areas might keep the potential to reappear in the human population after several years to cause a pandemic as it had happened in 1977.


Recovery from sports-related concussion: Days to return to neurocognitive baseline in adolescents versus young adults.
Sports-related concussions (SRC) among high school and collegiate athletes represent a significant public health concern. The Concussion in Sport Group (CIS) recommended greater caution regarding return to play with children and adolescents. We hypothesized that younger athletes would take longer to return to neurocognitive baseline than older athletes after a SRC. Two hundred adolescent and young adult athletes who suffered a SRC were included in our clinical research cohort. Of the total participants, 100 were assigned to the 13-16 year age group and 100 to the 18-22 year age group and were matched on the number of prior concussions. Each participant completed baseline and postconcussion neurocognitive testing using the Immediate Post-Concussion assessment and Cognitive Testing (ImPACT) test battery. Return to baseline was defined operationally as post-concussion neurocognitive and symptom scores being equivalent to baseline using reliable change index (RCI) criteria. For each group, the average number of days to return to cognitive and symptom baseline were calculated. Independent sample t-tests were used to compare the mean number of days to return to baseline. Significant differences were found for days to return to baseline between 13-16 year olds and 18-22 year olds in three out of four neurocognitive measures and on the total symptom score. The average number of days to return to baseline was greater for 13-16 year olds than for 18-22 year olds on the following variables: Verbal memory (7.2 vs. 4.7, P = 0.001), visual memory (7.1 vs. 4.7, P = 0.002), reaction time (7.2 vs. 5.1 P = 0.01), and postconcussion symptom scale (8.1 vs. 6.1, P = 0.026). In both groups, greater than 90% of athletes returned to neurocognitive and symptom baseline within 1 month. Our results in this clinical research study show that in SRC, athletes 13-16 years old take longer to return to their neurocognitive and symptom baselines than athletes 18-22 years old.


Optimization of magnetic neurostimulation waveforms for minimum power loss.
Magnetic stimulation is a key tool in experimental brain research and several clinical applications. Whereas coil designs and the spatial field properties have been intensively studied in the literature, the temporal dynamics of the field has received little attention. The available pulse shapes are typically determined by the relatively limited capabilities of commercial stimulation devices instead of efficiency or optimality. Furthermore, magnetic stimulation is relatively inefficient with respect to the required energy compared to other neurostimulation techniques. We therefore analyze and optimize the waveform dynamics with a nonlinear model of a mammalian motor axon for the first time, without any pre-definition of waveform candidates. We implemented an unbiased and stable numerical algorithm using variational calculus in combination with a global optimization method. This approach yields very stable results with comprehensible characteristic properties, such as a first phase which reduces ohmic losses in the subsequent pulse phase. We compare the energy loss of these optimal waveforms with the waveforms generated by existing magnetic stimulation devices.


The Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support 2023 Annual Report: Focus on Magnetically Levitated Devices.
The 14th Annual Report from The Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) describes outcomes of 27,493 patients with a continuous-flow left ventricular assist device (LVAD) from the past decade (2013-2022). In 2022, 2517 primary LVADs were implanted, of which 2512 (99.8%) were fully magnetically levitated (Mag-Lev) devices. This shift to nearly exclusive use of a Mag-Lev device led us to examine its outcomes compared with contemporary (2018-2022) and historical (2013-2017) non-Mag-Lev cohorts. Patients supported by a Mag-Lev device (n = 10,920) had a higher 1- and 5-year survival of 86% (vs 79% and 81%, P < .0001) and 64% (vs 44% and 44%, P < .0001), respectively, than those receiving non-Mag-Lev devices during the contemporary and historical eras. Over 5 years, freedom from gastrointestinal bleeding (72% vs 60%, P < .0001), stroke (87% vs 67%, P < .0001), and device malfunction/pump thrombus (83% vs 54%, P < .0001), but not device-related infection (61% vs 64%, P = .93), was higher with Mag-Lev devices compared with non-Mag-Lev support during the contemporary era. In this large primacy cohort of real-world patients with advanced heart failure, this report underscores marked improvements in short- and intermediate-term survival and reduction of adverse events with a contemporary Mag-Lev LVAD.


A comparison of on-site and off-site patent ductus arteriosus ligation in premature infants.
Persistent patent ductus arteriosus (PDA) often produces hemodynamic and respiratory derangement necessitating use of inotropic drugs and escalating ventilatory support in premature infants. When medical therapy fails, surgical ligation is indicated. Because of the risks of transferring unstable neonates to the operating room, ductal ligation is routinely performed at the neonatal intensive care unit (NICU) bedside. Some patients, however, require transfer from hospitals without pediatric cardiac surgical teams. In an attempt to eliminate the risks associated with transfer, a surgical team from our institution offered to perform duct ligation in the NICUs of referring institutions. This experienced team consisted of a pediatric cardiac attending anesthesiologist and certified registered nurse anesthetist, cardiac operating room nurses, an attending cardiothoracic surgeon, and a cardiothoracic surgery fellow. We retrospectively reviewed our experience. After approval from the Committee for the Protection of Human Subjects, the charts of premature neonates who underwent PDA ligation in the NICU at the Children's Hospital of Philadelphia NICU or in a network NICU between January 1996 and April 2002 were reviewed. Data abstracted included institution, gender, gestational age, birth weight, weight at surgery, and number of courses of indomethacin. Mean arterial blood pressure and use of inotropic drugs and ventilatory parameters (fraction of inspired oxygen, peak inspiratory pressure) were recorded at the time of surgery and 96 hours postoperatively. Perioperative complications were recorded. Seventy-two patients met the criteria for inclusion. PDA ligation was performed in the Children's Hospital of Philadelphia NICU in 38 of 72 patients, 53% (group 1). The remainder, 34 of 72 (47%) underwent PDA ligation in the NICU at 1 of 6 referring institutions (group 2). There were no significant differences between groups with respect to demographics, number of courses of indomethacin, or use of inotropic drugs or ventilatory support. The incidence of perioperative complications did not differ between groups: 3 in group 1 (bleeding, chylothorax, and pleural effusion) and 3 in group 2 (pneumothorax [3]). There were no anesthetic-related complications. Seven patients died (4 in group 1 and 3 in group 2), none within 96 hours of surgery and none secondary to the procedure. The data demonstrate that an experienced team can perform PDA ligation safely in NICUs of hospitals without on-site pediatric cardiac surgical capabilities in critically ill neonates without incurring the risks inherent in patient transport. Most importantly, patient care is continued by the neonatology team most familiar with the infant's medical and social history, and the patient's family is minimally inconvenienced.


Lipidomics based on liquid chromatography-high resolution mass spectrometry reveals the protective role of peroxisome proliferator-activated receptor alpha on kidney stone formation in mice treated with glyoxylate.
Few studies have examined the relationship between lipid metabolism and kidney stone formation, particularly the role of key lipid regulatory factors in kidney stone formation. We evaluated the effect of the lipid regulatory factor-peroxisome proliferator-activated receptor alpha on the formation of renal stones in mice by injecting them with glyoxylate followed by treatment with either a peroxisome proliferator-activated receptor alpha agonist fenofibrate or an antagonist GW6471 (GW). Liquid chromatography coupled with trapped ion mobility spectrometry-quadrupole-time-of-flight mass spectrometry-based lipidomics was used to determine the lipid profile in the mouse kidneys. Histological and biochemical analyses showed that the mice injected with glyoxylate exhibited crystal precipitation and renal dysfunction. Crystallization decreased significantly in the fenofibrate group, whereas it increased significantly in the GW group. A total of 184 lipids, including fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids differed significantly between the mice in the model and control groups. Peroxisome proliferator-activated receptor alpha activity negatively correlated with glyoxylate-induced kidney stone formation in mice, which may be related to improved fatty acid oxidation, maintenance of ceramide/complex sphingolipids cycle balance, and alleviation of disorder in phospholipid metabolism.


Methylenetetrahydrofolate reductase (MTHFR) gene C677T (rs1801133) polymorphism and risk of alcohol dependence: a meta-analysis.
Alcohol dependence is a complex neuropsychiatric disorder. Numerous studies investigated association between MTHFR gene C677T (rs1801133) polymorphism and alcohol dependence (AD), but the results of this association remain conflicting. Accordingly, authors conducted a meta-analysis to further investigate such an association. PubMed, Elsevier Science Direct and Springer Link databases were searched for studies on the association between the MTHFRC677T polymorphism and AD. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed- or random-effects model. Statistical analysis was performed with the software program MetaAnayst and MIX.A total of 11 articles were identified through a search of electronic databases, up to February 28, 2020. The results of the present meta-analysis did not show any association between MTHFR C677T polymorphisms and AD risk (for T vs. C: OR = 1.04, 95% CI = 0.88-1.24; CT vs. CC: OR = 1.02, 95% CI = 0.62-1.68; for TT+CT vs. CC: OR = 1.10, 95% CI = 0.94-1.29; for TT vs. CC: OR = 1.01, 95% CI = 0.66-1.51; for TT vs. CT+CC: OR = 0.97, 95% CI = 0.66-1.40). Results of subgroup analysis showed no significant association between MTHFR C677T polymorphism with AD in Asian as well as in Caucasian population. In conclusion, C677T polymorphism is not a risk factor for alcohol dependence.


Microarray analysis of adipose tissue gene expression profiles between two chicken breeds.
The chicken is an important model organism that bridges the evolutionary gap between mammals and other vertebrates and provides a major protein source from meat and eggs throughout the world. Excessive accumulation of lipids in the adipose tissue is one of the main problems faced by the broiler industry nowadays. In order to visualize the mechanisms involved in the gene expression and regulation of lipid metabolism in adipose tissue, cDNA microarray containing 9024 cDNA was used to construct gene expression profile and screen differentially expressed genes in adipose tissue between broilers and layers of 10 wk of age. Sixty-seven differentially expressed sequences were screened out, and 42 genes were found when blasted with the GenBank database. These genes are mainly related to lipid metabolism, energy metabolism, transcription and splicing factor, protein synthesis and degradation. The remained 25 sequences had no annotation available in the GenBank database. Furthermore, Northern blot and semi-quantitative RT-PCR were developed to confirm 4 differentially expressed genes screened by cDNA microarray, and it showed great consistency between the microarray data and Northern blot results or semi-quantitative RT-PCR results. The present study will be helpful for clarifying the molecular mechanism of obesity in chickens.


Home monitor follow-up of persistent apnea and bradycardia in preterm infants.
We reviewed our experience with home monitor observations of 83 preterm infants (postconceptional age, 36 to 44 weeks) who had persistent apnea, bradycardia, or cyanosis. Polygraphic recordings before discharge showed that 92% of these infants had cardiorespiratory abnormalities that included prolonged (greater than 20 s) apnea, excessive periodic breathing (greater than 15%), bradycardia (greater than 80 beats per minute), feeding hypoxemia, or elevated carbon dioxide values. At home, 70 infants had either no alarms or alarms that resolved spontaneously, while 13 (16%) had more serious episodes that required parental intervention, including mouth-to-mouth ventilation in one infant. While polygraphic studies were helpful in documenting specific cardiorespiratory abnormalities, neither these abnormalities nor the clinical characteristics of the infants identified those infants experiencing subsequent home monitor alarms requiring parental intervention. Our data suggest that some preterm infants with persistent episodes of apnea, bradycardia, and cyanosis beyond 36 weeks of postconceptional age remain at risk for future serious episodes for several months.


Comparison of plant diversity-carbon storage relationships along altitudinal gradients in temperate forests and shrublands.
Understanding the mechanisms underlying the relationship between biodiversity and ecosystem function (BEF) is critical for the implementation of productive and resilient ecosystem management. However, the differences in BEF relationships along altitudinal gradients between forests and shrublands are poorly understood, impeding the ability to manage terrestrial ecosystems and promote their carbon sinks. Using data from 37962 trees of 115 temperate forest and 134 shrubland plots of Taihang Mountains Priority Reserve, we analyzed the effects of species diversity, structural diversity, climate factors and soil moisture on carbon storage along altitudinal gradients in temperate forests and shrublands. We found that: (1) Structural diversity, rather than species diversity, mainly promoted carbon storage in forests. While species diversity had greater positive effect on carbon storage in shrublands. (2) Mean annual temperature (MAT) had a direct negative effect on forest carbon storage, and indirectly affected forest carbon storage by inhibiting structural diversity. In contrast, MAT promoted shrubland carbon storage directly and indirectly through the positive mediating effect of species diversity. (3) Increasing altitudinal gradients enhanced the structural diversity-carbon relationship in forests, but weakened the species diversity-carbon relationship in shrublands. Niche and architectural complementarity and different life strategies of forests and shrubs mainly explain these findings. These differential characteristics are critical for our comprehensive understanding of the BEF relationship and could help guide the differentiated management of forests and shrublands in reaction to environmental changes.


Effect of carbohydrate intake on net muscle protein synthesis during recovery from resistance exercise.
The purpose of this study was to determine the effect of ingestion of 100 g of carbohydrates on net muscle protein balance (protein synthesis minus protein breakdown) after resistance exercise. Two groups of eight subjects performed a resistance exercise bout (10 sets of 8 repetitions of leg presses at 80% of 1-repetition maximum) before they rested in bed for 4 h. One group (CHO) received a drink consisting of 100 g of carbohydrates 1 h postexercise. The other group (Pla) received a noncaloric placebo drink. Leg amino acid metabolism was determined by infusion of 2H5- or 13C6-labeled phenylalanine, sampling from femoral artery and vein, and muscle biopsies from vastus lateralis. Drink intake did not affect arterial insulin concentration in Pla, whereas insulin increased several times after the drink in CHO (P < 0.05 vs. Pla). Arterial phenylalanine concentration fell slightly after the drink in CHO. Net muscle protein balance between synthesis and breakdown did not change in Pla, whereas it improved in CHO from -17 +/- 3 nmol.ml(-1).100 ml leg(-1) before drink to an average of -4 +/- 4 and 0 +/- 3 nmol.ml(-1).100 ml leg(-1) during the second and third hour after the drink, respectively (P < 0.05 vs. Pla during last hour). The improved net balance in CHO was due primarily to a progressive decrease in muscle protein breakdown. We conclude that ingestion of carbohydrates improved net leg protein balance after resistance exercise. However, the effect was minor and delayed compared with the previously reported effect of ingestion of amino acids.


Cerebellar Haemorrhage Leading to Sudden Cardiac Arrest.
Intracranial haemorrhage (ICH) is a known, but a rare cause of out of hospital cardiac arrest (OHCA). It results in the development of non-shockable rhythms such as asystole or pulseless electrical activity (PEA). A 77- years old male had an OHCA without any prodrome. An emergency medical services (EMS) team responded to an emergency call and intubated the patient at the site before transporting him to the Acute Care Hospital, New Brunswick, New Jersey, USA. On admission, a non-contrast computed tomography scan of the head revealed a large cerebellar haemorrhage. Non-traumatic ICH is a rare cause of OHCA. Although subarachnoid haemorrhage causing cardiac arrest has been described in the literature, cerebellar haemorrhage leading to cardiac arrest is rare. The mechanism by which ICH patients develop cardiac arrest is likely explained by a massive catecholamine surge leading to cardiac stunning. A non-shockable rhythm in the seting of a sudden cardiac arrest should raise alarms for a primary non-cardiac ethology, especially a primary cerebrovascular event. The absence of brainstem reflexes increases the likelihood of an intracranial process.


Radioautographic localization of sodium pump sites in rabbit intestine.
Direct demonstration of the cellular location of sodium pumping constitutes a key problem in the solution of intestinal sodium absorption. Utilizing silicone-impregnated epoxy sections of freeze-dried, osmium-fixed tissue, ouabain-(3)H and inulin-(3)H light microscope radioautographs have been produced which show that: lateral but not brush border membranes of rabbit small intestine bind ouabain-(3)H (high specific activity) with an affinity so great that a subsequent washing in ouabain-free medium has little effect on binding; lateral membrane binding is not apparent with low specific activity ouabain-(3)H, and inulin-(3)H and ouabain-(3)H (low specific activity) in the cores of the villi do not equilibrate with the intercellular spaces. Preliminary tracer measurements of ouabain-(3)H and inulin-(14)C spaces also agree with these findings As ouabain is a specific inhibitor of active sodium transport, these observations provide direct support for the view that lateral membrane pumping of sodium into the intercellular spaces causes, through osmotic forces on water, a flow of fluid out of these spaces into the interstitium.


[Ratio of spontaneous and o-aminoazotoluene-induced hepatocarcinogenesis in mice].
No correlation was found between the frequency of spontaneous and o-aminoazotoluene (o-AAT)-induced hepatic tumours in mice. High susceptibility to tumour induction with o-AAT in mice both genetically susceptible (strains CBA and A/He) and resistant (strains DBA/2J and DD) to spontaneous hepatocarcinogenesis was detected. The CC57BR mice predisposed to spontaneous hepatomas were insensitive to their induction with o-AAT. The model described may be helpful in studies of the nature of the initiation and promotion stages of hepatocarcinogenesis.


Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings.
In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon. Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR. Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases. Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians' diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection.


Lining bunker walls with oxygen barrier film reduces nutrient losses in corn silages.
The objective of this study was to evaluate 2 systems for covering corn silage in bunker silos. The first system consisted of a sheet of 45-μm-thick oxygen barrier film (OB, polyethylene + ethylene-vinyl alcohol) placed along the length of the sidewall before filling. After filling, the excess film was pulled over the wall on top of the silage, and a sheet of polyethylene was placed on top. The second system involved using a standard sheet (ST) of 180-μm-thick polyethylene film. Eight commercial bunker silos were divided into 2 parts lengthwise so that one-half of the silo was covered with OB and the other half with a ST system. During the filling, 3 net bags with chopped corn were buried in the central part (halfway between the top and bottom of the silo) of the bunkers (CCOR) in 3 sections 10 m apart. After filling, 18 net bags (9 per covering system) were buried 40 cm below the top surface of the 3 sections. These bags were placed at 3 distances from the bunker walls (0 to 50 cm, 51 to 100 cm, and 101 to 150 cm). During unloading, the bags were removed from the silos to determine the dry matter (DM) losses, fermentation end products, and nutritive value. The Milk2006 spreadsheet was used to estimate milk per tonne of DM. The model included the fixed effect of treatment (7 different locations in the bunker) and the random effect of the silo. Two contrasts were tested to compare silages in the top laterals (shoulders) with that in the CCOR (CCOR vs. OB and CCOR vs. ST). Three contrasts compared the corresponding distances of the silage covered by the 2 systems (OB50 vs. ST50, OB100 vs. ST100 and OB150 vs. ST150). Variables were analyzed with the PROC MIXED procedure of the SAS at the 5% level. The OB method produced well-fermented silages, which were similar to CCOR, whereas the OB system showed less lactic acid and greater pH and mold counts compared with CCOR. The ST method had 116.2 kg of milk/t less than the CCOR, as the OB system and the CCOR were similar (1,258.3 and 1,294.0 kg/t, respectively). Regarding the distances from the walls, the effects were more pronounced from 0 to 101 cm. The OB50 and OB100 silages had better quality and lower mold counts and DM losses than ST50 and ST100. The OB system reduced DM and nutrient losses at the shoulders in farm bunker corn silages compared with no sidewall plastic. The OB film should lap onto the crop for at least 200 cm so that 150 cm are covered outward from the wall.


Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study.
Most tuberculosis-related deaths in people with HIV could be prevented with earlier diagnosis and treatment. The only commercially available tuberculosis point-of-care test (Alere Determine TB LAM Ag [AlereLAM]) has suboptimal sensitivity, which restricts its use in clinical practice. The novel Fujifilm SILVAMP TB LAM (FujiLAM) assay has been developed to improve the sensitivity of AlereLAM. We assessed the diagnostic accuracy of the FujiLAM assay for the detection of tuberculosis in hospital inpatients with HIV compared with the AlereLAM assay. For this diagnostic accuracy study, we assessed biobanked urine samples obtained from the FIND Specimen Bank and the University of Cape Town Biobank, which had been collected from hospital inpatients (aged ≥18 years) with HIV during three independent prospective cohort studies done at two South African hospitals. Urine samples were tested using FujiLAM and AlereLAM assays. The conduct and reporting of each test was done blind to other test results. The primary objective was to assess the diagnostic accuracy of FujiLAM compared with AlereLAM, against microbiological and composite reference standards (including clinical diagnoses). Between April 18, 2018, and May 3, 2018, urine samples from 968 hospital inpatients with HIV were evaluated. The prevalence of microbiologically-confirmed tuberculosis was 62% and the median CD4 count was 86 cells per μL. Using the microbiological reference standard, the estimated sensitivity of FujiLAM was 70·4% (95% CI 53·0 to 83·1) compared with 42·3% (31·7 to 51·8) for AlereLAM (difference 28·1%) and the estimated specificity of FujiLAM was 90·8% (86·0 to 94·4) and 95·0% (87·7-98·8) for AlereLAM (difference -4·2%). Against the composite reference standard, the specificity of both assays was higher (95·7% [92·0 to 98·0] for FujiLAM vs 98·2% [95·7 to 99·6] for AlereLAM; difference -2·5%), but the sensitivity of both assays was lower (64·9% [50·1 to 76·7] for FujiLAM vs 38·2% [28·1 to 47·3] for AlereLAM; difference 26·7%). In comparison to AlereLAM, FujiLAM offers superior diagnostic sensitivity, while maintaining specificity, and could transform rapid point-of-care tuberculosis diagnosis for hospital inpatients with HIV. The applicability of FujiLAM for settings of intended use requires prospective assessment. Global Health Innovative Technology Fund, UK Department for International Development, Dutch Ministry of Foreign Affairs, Bill & Melinda Gates Foundation, German Federal Ministry of Education and Research, Australian Department of Foreign Affairs and Trade, Wellcome Trust, Department of Science and Technology and National Research Foundation of South Africa, and South African Medical Research Council.


Nitric oxide synthase gene transfer overcomes the inhibition of wound healing by sulfur mustard in a human keratinocyte in vitro model.
Sulfur mustard (SM) is a chemical warfare agent that causes extensive skin injury. Previously we reported that SM exposure resulted in suppression of inducible nitric oxide synthase (iNOS) expression to inhibit the healing of scratch wounds in a cultured normal human epidermal keratinocyte (NHEK) model. Based on this finding, the present study was to use adenovirus-mediated gene transfer of iNOS to restore the nitric oxide (NO) supply depleted by exposure to SM and to evaluate the effect of NO on wound healing inhibited by SM in NHEKs. The effect of the iNOS gene transfer on iNOS protein expression and NO generation were monitored by Western blot and flow cytometry, respectively. Wound healing with or without the iNOS gene transfer after SM exposure was assessed by light and confocal microscopy. The iNOS gene transfer via adenovirus resulted in overexpression of the iNOS and an increase in NO production regardless of SM exposure in the NHEK model. The gene transfer was also effective in overcoming the inhibition of wound healing due to SM exposure leading to the promotion of wound closure. The findings in this study suggest that the iNOS gene transfer is a promising therapeutic strategy for SM-induced skin injury.


Clinical outcomes of globus pallidus deep brain stimulation for Parkinson disease: a comparison of intraoperative MRI- and MER-guided lead placement.
Deep brain stimulation (DBS) lead placement is increasingly performed with the patient under general anesthesia by surgeons using intraoperative MRI (iMRI) guidance without microelectrode recording (MER) or macrostimulation. The authors assessed the accuracy of lead placement, safety, and motor outcomes in patients with Parkinson disease (PD) undergoing DBS lead placement into the globus pallidus internus (GPi) using iMRI or MER guidance. The authors identified all patients with PD who underwent either MER- or iMRI-guided GPi-DBS lead placement at Emory University between July 2007 and August 2016. Lead placement accuracy and adverse events were determined for all patients. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor scores for patients completing 12 months of follow-up. The authors also assessed the levodopa-equivalent daily dose (LEDD) and stimulation parameters. Seventy-seven patients were identified (MER, n = 28; iMRI, n = 49), in whom 131 leads were placed. The stereotactic accuracy of the surgical procedure with respect to the planned lead location was 1.94 ± 0.21 mm (mean ± SEM) (95% CI 1.54-2.34) with frame-based MER and 0.84 ± 0.007 mm (95% CI 0.69-0.98) with iMRI. The rate of serious complications was similar, at 6.9% for MER-guided DBS lead placement and 9.4% for iMRI-guided DBS lead placement (RR 0.71 [95% CI 0.13%-3.9%]; p = 0.695). Fifty-seven patients were included in clinical outcome analyses (MER, n = 16; iMRI, n = 41). Both groups had similar characteristics at baseline, although patients undergoing MER-guided DBS had a lower response on their baseline levodopa challenge (44.8% ± 5.4% [95% CI 33.2%-56.4%] vs 61.6% ± 2.1% [95% CI 57.4%-65.8%]; t = 3.558, p = 0.001). Greater improvement was seen following iMRI-guided lead placement (43.2% ± 3.5% [95% CI 36.2%-50.3%]) versus MER-guided lead placement (25.5% ± 6.7% [95% CI 11.1%-39.8%]; F = 5.835, p = 0.019). When UPDRS III motor scores were assessed only in the contralateral hemibody (per-lead analyses), the improvements remained significantly different (37.1% ± 7.2% [95% CI 22.2%-51.9%] and 50.0% ± 3.5% [95% CI 43.1%-56.9%] for MER- and iMRI-guided DBS lead placement, respectively). Both groups exhibited similar reductions in LEDDs (21.2% and 20.9%, respectively; F = 0.221, p = 0.640). The locations of all active contacts and the 2D radial distance from these to consensus coordinates for GPi-DBS lead placement (x, ±20; y, +2; and z, -4) did not differ statistically by type of surgery. iMRI-guided GPi-DBS lead placement in PD patients was associated with significant improvement in clinical outcomes, comparable to those observed following MER-guided DBS lead placement. Furthermore, iMRI-guided DBS implantation produced a similar safety profile to that of the MER-guided procedure. As such, iMRI guidance is an alternative to MER guidance for patients undergoing GPi-DBS implantation for PD.


Eukaryote-specific insertion elements control human ARGONAUTE slicer activity.
We have solved the crystal structure of human ARGONAUTE1 (hAGO1) bound to endogenous 5'-phosphorylated guide RNAs. To identify changes that evolutionarily rendered hAGO1 inactive, we compared our structure with guide-RNA-containing and cleavage-active hAGO2. Aside from mutation of a catalytic tetrad residue, proline residues at positions 670 and 675 in hAGO1 introduce a kink in the cS7 loop, forming a convex surface within the hAGO1 nucleic-acid-binding channel near the inactive catalytic site. We predicted that even upon restoration of the catalytic tetrad, hAGO1-cS7 sterically hinders the placement of a fully paired guide-target RNA duplex into the endonuclease active site. Consistent with this hypothesis, reconstitution of the catalytic tetrad with R805H led to low-level hAGO1 cleavage activity, whereas combining R805H with cS7 substitutions P670S and P675Q substantially augmented hAGO1 activity. Evolutionary amino acid changes to hAGO1 were readily reversible, suggesting that loading of guide RNA and pairing of seed-based miRNA and target RNA constrain its sequence drift.


Social anxiety and alcohol-related impairment: The mediational impact of solitary drinking.
Social anxiety disorder more than quadruples the risk of developing an alcohol use disorder, yet it is inconsistently linked to drinking frequency. Inconsistent findings may be at least partially due to lack of attention to drinking context - it may be that socially anxious individuals are especially vulnerable to drinking more often in specific contexts that increase their risk for alcohol-related problems. For instance, socially anxious persons may drink more often while alone, before social situations for "liquid courage" and/or after social situations to manage negative thoughts about their performance. Among current (past-month) drinkers (N=776), social anxiety was significantly, positively related to solitary drinking frequency and was negatively related to social drinking frequency. Social anxiety was indirectly (via solitary drinking frequency) related to greater past-month drinking frequency and more drinking-related problems. Social anxiety was also indirectly (via social drinking frequency) negatively related to past-month drinking frequency and drinking-related problems. Findings suggest that socially anxious persons may be vulnerable to more frequent drinking in particular contexts (in this case alone) and that this context-specific drinking may play an important role in drinking problems among these high-risk individuals.


Copper(II) binding to dissolved organic matter fractions in municipal solid waste incinerator bottom ash leachate.
Information on Cu speciation in municipal solid waste incineration (MSWI) bottom ash leachate is needed for Cu leaching predictions and toxicity estimates. The complexation of Cu with dissolved organic matter (DOM) in leachates from a stored MSWI bottom ash was studied potentiometrically using a Cu-ion selective electrode. More than 95% of the copper was bound to DOM in the hydrophilic fraction of the leachate, indicating that the hydrophilic acids contribute to Cu complex formation. The hydrophilic acids constituted 58% of the dissolved organic carbon in the ash leachate. Comparisons between experimental results and speciation calculations with the NICA-Donnan model and the Stockholm humic model indicated differences between the ash DOM and the natural DOM for which the models have been calibrated. The ratio of carboxylic binding sites to phenolic binding sites was 2 times larger in ash DOM, and the Cu-binding affinity of the former was stronger than accounted for by the generic Cu-binding parameters. The Cu-binding affinity of the phenolic sites, on the other hand, was weaker. When these parameters were adjusted, a good description of the experimental data was obtained.


Ecomorphology of the African felid ensemble: the role of the skull and postcranium in determining species segregation and assembling history.
Morphology of extant felids is regarded as highly conservative. Most previous studies have focussed on skull morphology, so a vacuum exists about morphofunctional variation in postcranium and its role in structuring ensembles of felids in different continents. The African felid ensemble is particularly rich in ecologically specialized felids. We studied the ecomorphology of this ensemble using 31 cranial and 93 postcranial morphometric variables measured in 49 specimens of all 10 African species. We took a multivariate approach controlling for phylogeny, with and without body size correction. Postcranial and skull + postcranial analyses (but not skull-only analyses) allowed for a complete segregation of species in morphospace. Morphofunctional factors segregating species included body size, bite force, zeugopodial lengths and osteological features related to parasagittal leg movement. A general gradient of bodily proportions was recovered: lightly built, long-legged felids with small heads and weak bite forces vs. the opposite. Three loose groups were recognized: small terrestrial felids, mid-to-large sized scansorial felids and specialized Acinonyx jubatus and Leptailurus serval. As predicted from a previous study, the assembling of the African felid ensemble during the Plio-Pleistocene occurred by the arrival of distinct felid lineages that occupied then vacant areas of morphospace, later diversifying in the continent.


Weight of foods and number of portions consumed are not proxies for expressing nutrient intakes in field studies.
In order to determine whether simplified indicators for usual consumption of selected food groups, specifically those derived from either the percentage of the number of daily portions, the percentage of total daily weight consumed, or both, could serve as proxies for the conventional expression of daily energy intake, these indicators were computed and compared from food-frequency data in a data set. Food consumption was reported in frequency categories and portion sizes per month, per week, or per day, and the cumulative sum was divided by 365 to provide a daily average. The survey was done in the township of Santa Cruz and three hamlets of a rural county seat in Guatemala. Data from food-frequency questionnaires from 269 individuals (55 men and 214 women aged 16 to 86 years) were analyzed. For foods of plant origin, the percentage of total energy, percentage of total food weight, and percentage of total number of portions consumed showed low correlations (r < .45). When subdivided into specific foods and food groups (fruits and vegetables, red meat, etc.), marked differences were revealed across sites and among different indicators of consumption. Despite the simplicity of calculation, neither the percentage of weight of food in a group nor the percentage of portions consumed could serve reliably as proxies for their contributions to the percentage of total energy in this rural population in Guatemala.


[Phenytoin and phenytoin derivatives for local administration].
A well known side effect of the long-term therapy with phenytoin is gum hyperplasia. 1-Acyl compounds and esters of the p-hydroxymetabolite with aliphatic and aromatic carboxylic acids were synthesized as potential prodrugs for therapeutic use if the neoformation of connective tissue is intended. The compounds were characterized by there physico-chemical constants and the absorption was proofed by a buccal test.


A Retrospective Case-Matched Cost Comparison of Surgical Treatment of Melanoma and Nonmelanoma Skin Cancer in the Outpatient Versus Operating Room Setting.
To date, no study has used authentic billing data in a case-control matched fashion to examine the cost of treating skin cancer in different settings. To compare the cost of surgical treatment of skin cancer in the outpatient versus operating room setting using matched cases based on patient and skin cancer characteristics. ICD-9 diagnosis codes for skin cancers were used to find patients who had a malignant excision current procedural terminology code in the operating room setting during 2010 to 2014. Patient and skin cancer characteristics were used to match cases to those treated as an outpatient. A total of 36 cases (18 operating room and 18 outpatient) had the required information and characteristics to be matched and analyzed for cost. Health status was determined using the American Society of Anesthesiologists anesthesia grading scale. No statistically significant differences were found in the age (p > 0.9) or American Society of Anesthesiologists scores (p > 0.6) of the outpatient and operating room cases. The median cost for outpatient cases was $1,745. For operating room cases, the median cost was $11,323. This was a statistically significant difference (p < 0.001). The outpatient setting remains a cost-effective location to treat skin cancer compared with the operating room.


Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS).
Delayed gastric emptying (DGE) is one of the most common complications after pancreatic resection. In the literature, the reported incidence of DGE after pancreatic surgery varies considerably between different surgical centers, primarily because an internationally accepted consensus definition of DGE is not available. Several surgical centers use a different definition of DGE. Hence, a valid comparison of different study reports and operative techniques is not possible. After a literature review on DGE after pancreatic resection, the International Study Group of Pancreatic Surgery (ISGPS) developed an objective and generally applicable definition with grades of DGE based primarily on severity and clinical impact. DGE represents the inability to return to a standard diet by the end of the first postoperative week and includes prolonged nasogastric intubation of the patient. Three different grades (A, B, and C) were defined based on the impact on the clinical course and on postoperative management. The proposed definition, which includes a clinical grading of DGE, should allow objective and accurate comparison of the results of future clinical trials and will facilitate the objective evaluation of novel interventions and surgical modalities in the field of pancreatic surgery.


Comparison of the Efficacy of a Sulfuric Acid-Sodium Sulfate Blend and Lactic Acid for the Reduction of Salmonella on Prerigor Beef Carcass Surface Tissue.
A study was conducted to compare the efficacy of a commercially available sulfuric acid-sodium sulfate blend (SSS) and lactic acid (LA) in reducing inoculated Salmonella populations on beef. Sixty pieces of prerigor beef carcass surface brisket tissue, collected directly from the processing line of a commercial beef processing plant, were cut into two sections (10 by 10 cm each) and spot inoculated (6 to 7 log CFU/cm2) on the adipose side with a six-strain mixture of Salmonella. One section per piece of brisket tissue was left untreated (control), while the second section was spray treated (5 s, 15 lb/in2, and 33 mL/s flow rate) with unheated (21°C) or heated (52°C) solutions of SSS (pH 1.1) or LA (4%). Unheated and heated SSS lowered (P < 0.05) total bacterial counts from 6.3 to 4.6 and 4.3 log CFU/cm2, respectively. Likewise, unheated and heated LA reduced (P < 0.05) total bacterial counts from 6.3 to 4.7 and 4.4 log CFU/cm2, respectively. Initial counts of inoculated Salmonella populations (6.1 to 6.2 log CFU/cm2) were reduced (P < 0.05) to 4.2 and 3.9 log CFU/cm2 following treatment with unheated and heated SSS, respectively, and to 3.7 and 3.8 log CFU/cm2 after treatment with unheated and heated LA, respectively. Overall, the temperature of the chemical solutions had a small (0.3 log CFU/cm2), but significant (P < 0.05), effect on total bacterial counts but not (P > 0.05) on Salmonella counts. Regardless of solution temperature, Salmonella counts for LA-treated samples were 0.3 log CFU/cm2 lower (P < 0.05) than those of samples treated with SSS. These results indicate that both unheated and heated solutions of SSS and LA are effective interventions for reducing Salmonella contamination on prerigor beef carcass surface tissue.


Going direct to the consumer: Examining treatment preferences for veterans with insomnia, PTSD, and depression.
Inclusion of consumer preferences to disseminate evidence-based psychosocial treatment (EBPT) is crucial to effectively bridge the science-to-practice quality chasm. We examined this treatment gap for insomnia, posttraumatic stress disorder (PTSD), depression, and comorbid symptoms in a sample of 622 young adult veterans through preference in symptom focus, treatment modality, and related gender differences among those screening positive for each problem. Data were collected from veteran drinkers recruited through targeted Facebook advertisements as part of a brief online alcohol intervention. Analyses demonstrated that veterans reported greater willingness to seek insomnia-focused treatment over PTSD- or depression-focused care. Notably, even when participants screened negative for insomnia, they preferred sleep-focused care to PTSD- or depression-focused care. Although one in five veterans with a positive screen would not consider care, veterans screening for both insomnia and PTSD who would consider care had a preference for in-person counseling, and those screening for both insomnia and depression had similar preferences for in-person and mobile app-based/computer self-help treatment. Marginal gender differences were found. Incorporating direct-to-consumer methods into research can help educate stakeholders about methods to expand EBPT access. Though traditional in-person counseling was often preferred, openness to app-based/computer interventions offers alternative methods to provide veterans with EBPTs.


Integration of surgery and other techniques in the management of trophoblastic malignancy.
The role of surgery in the management of gestational trophoblastic neoplasms has changed over the years and warrants continuous re-evaluation. Surgical removal of the bulk of the disease in an attempt to shorten the hospital course and decrease the amount of chemotherapy required appears to be of value. This approach to therapy should therefore be considered in most patients with nonmetastatic disease without regard to the histologic diagnosis if they have completed their families. "Debulking" of primary uterine disease in the presence of metastases may decrease the chemotherapy necessary for cure and removes a potential source of resistant disease. Pulmonary surgery improves survival rates for patients with a solitary, resistant lung tumor and is advisable under the circumstances outlined herein. Craniotomy is rarely of value in the management of tumor in the brain but may be necessary in emergency situations caused by intracerebral hemorrhage. Surgery to control complications of the disease has been proved to be safe with acceptable morbidity even if performed during chemotherapy. Thus, although chemotherapy has replaced surgery as the primary management of patients with gestational trophoblastic disease, there remain a significant number of patients in whom surgery plays a significant role.


Primary structure and effect of pH on the expression of the plasma membrane H(+)-ATPase from Dunaliella acidophila and Dunaliella salina.
The plasma membrane H(+)-ATPase gene was cloned and sequenced from the extremely acidophilic green alga Dunaliella acidophila and from the extremely halotolerant Dunaliella salina. A special feature of the Dunaliella H(+)-ATPase is an extended C-terminal domain. The deduced amino acid sequences of the two proteins are 75% identical but differ in their C terminus. A hydrophilic loop within this domain in D. salina, which presumably faces the cell exterior, has a high ratio of acidic over basic amino acids, typical of halophilic proteins. The amount of the ATPase protein in plasma membranes and the level of its mRNA transcript in D. acidophila are far higher than in D. salina, suggesting that D. acidophila overexpresses the enzyme. A pH shift from 9.0 to 7.0 induces in D. salina a large increase in the level of the H(+)-ATPase mRNA and in the amount of the H(+)-ATPase protein. This suggests that the expression of the H(+)-ATPase in D. salina is pH-regulated at the transcriptional level. The implications of these findings are discussed with respect to the adaptive pressures imposed on these algal species by their exceptional environmental conditions.


New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication.
Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.


On the Origin of Biomolecular Networks.
Biomolecular networks have already found great utility in characterizing complex biological systems arising from pairwise interactions amongst biomolecules. Here, we explore the important and hitherto neglected role of information asymmetry in the genesis and evolution of such pairwise biomolecular interactions. Information asymmetry between sender and receiver genes is identified as a key feature distinguishing early biochemical reactions from abiotic chemistry, and a driver of network topology as biomolecular systems become more complex. In this context, we review how graph theoretical approaches can be applied not only for a better understanding of various proximate (mechanistic) relations, but also, ultimate (evolutionary) structures encoded in such networks from among all types of variations they induce. Among many possible variations, we emphasize particularly the essential role of gene duplication in terms of signaling game theory, whereby sender and receiver gene players accrue benefit from gene duplication, leading to a preferential attachment mode of network growth. The study of the resulting dynamics suggests many mathematical/computational problems, the majority of which are intractable yet yield to efficient approximation algorithms, when studied through an algebraic graph theoretic lens. We relegate for future work the role of other possible generalizations, additionally involving horizontal gene transfer, sexual recombination, endo-symbiosis, etc., which enrich the underlying graph theory even further.


Responsive polymers for biosensing and protein delivery.
In this feature article, we review some recent advances in the field of materials chemistry for biosensing, and protein/drug delivery. Our recent work on the development of responsive polymer-based platforms for biosensing and drug delivery will also be highlighted. This feature article is meant to outline the breadth of the utility of polymer-based materials for select applications, as well as their enormous potential impact on future technologies.


Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease.
Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers.


Paraduodenal hernia: a treatable cause of upper gastrointestinal tract symptoms.
Paraduodenal hernia (PDH) is an unusual condition that is caused by congenital intestinal malrotation. Noncatastrophic presenting symptoms and their responses to surgery have not been well-characterized. Barium upper gastrointestinal (UGI) series and small bowel follow-up x-rays, performed from December 1995 to September 1996, were sequentially reviewed by one radiologist (J.M.) to identify patients with small bowel series compatible with a PDH. Case histories were reviewed for symptomatic presentation, associated evaluation, and treatment. Based on the 294 UGIs and small bowel follow-throughs performed during this 10-month period, 6 cases were suspected to have a PDH. A right PDH was confirmed in the three patients who underwent surgical exploration (prevalence 1%). Preoperative patient symptoms included nausea, bilious vomiting, and right upper quadrant pain. Repair of the hernia defect resulted in complete resolution of chronic symptoms. Preoperative upper endoscopy, performed in three patients, was not helpful in identifying the disorder. Preoperative computerized tomography obtained in two patients was diagnostic for a right PDH. One symptomatic patient with vomiting and gastric stasis did not have surgery because of a terminal illness. The remaining two patients had no symptoms attributable to PDH. Patients with PDH frequently have chronic UGI symptoms. An upper endoscopy cannot be used to exclude this entity. After surgery, UGI symptoms from PDH are likely to resolve.


Chronic disease and its risk factors among refugees and asylees in Massachusetts, 2001-2005.
Better understanding of the health problems of refugees and people who are granted political asylum (asylees) in the United States may facilitate successful resettlement. We examined the prevalence of risk factors for and diagnoses of chronic disease among these groups in Massachusetts. We retrospectively analyzed health screening data from 4,239 adult refugees and asylees who arrived in Massachusetts from January 1, 2001, through December 31, 2005. We determined prevalence of obesity/overweight, hypertension, coronary artery disease (CAD), diabetes, and anemia. Analyses included multivariate logistic regression to determine associations between CAD and diabetes with region of origin. Almost half of our sample (46.8%) was obese/overweight, and 22.6% had hypertension. CAD, diabetes, and anemia were documented in 3.7%, 3.1%, and 12.8%, respectively. People from the Europe and Central Asia region were more likely than those from other regions to have CAD (odds ratio, 5.55; 95% confidence interval, 2.95-10.47). The prevalence of obesity/overweight and hypertension was high among refugees and asylees, but the prevalence of documented CAD and diabetes was low. We noted significant regional variations in prevalence of risk factors and chronic diseases. Future populations resettling in the United States should be linked to more resources to address their long-term health care needs and to receive culturally appropriate counseling on risk reduction.


Barriers and Pathways to Changing Smoking and Risky Drinking in Primary Care Patients With Chronic Conditions Who Failed to Respond to Brief Advice.
Objective: Many individuals who smoke tobacco or consume alcohol at hazardous levels have chronic conditions that are caused or exacerbated by these behaviors. The objective of this survey study was to obtain data on the health care concerns, barriers, and readiness to change indicators of smokers/risky drinkers with related health conditions who have not responded to standard primary care interventions. Methods: 167 participants (120 who reported current smoking or risky drinking or both) completed a 1-time mailed survey in 2017/2018. Participants were asked about smoking and drinking habits, physical health and impairments, health-related concerns, and barriers and readiness to change smoking and drinking. Results: For smokers and drinkers, the most common health concern was cardiovascular related (22% and 19%, respectively), though co-users were more concerned about pain. The most common barriers to change were lacking motivation and belief that alcohol/tobacco was not impacting their health. For smokers and drinkers, stronger beliefs that smoking/drinking does not affect their health was associated with lower importance of changing. Conclusions: Data from this study suggest that the main reasons patients report not changing are based on deficits in motivation and likely in information. In a group of patients who all have conditions that contraindicate smoking and risky drinking, their belief that their behaviors do not cause problems and that their health is not affected by their behaviors suggests a need for increased, focused education.


Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer.
Capecitabine is a novel, oral, selectively tumor-activated fluoropyrimidine carbamate. This large multicenter phase II trial tested the efficacy and safety of twice-daily oral capecitabine at 2,510 mg/m2/d given for 2 weeks followed by a 1-week rest period and repeated in 3-week cycles, in patients with paclitaxel-refractory metastatic breast cancer. Patients were to have received at least two but not more than three prior chemotherapeutic regimens, one of which had to have contained paclitaxel given for metastatic disease. One hundred sixty-three patients were entered onto the study at 25 centers, and 162 patients received capecitabine. One hundred thirty-five patients had bidimensionally measurable disease, and 27 patients had assessable disease. The overall response rate was 20% (95% confidence interval, 14% to 28%). All responding patients were resistant to or had failed paclitaxel, and all had received an anthracycline. Three complete responses were seen, with complete response durations of 106, 109, and 194+ days. Median duration of response was 8.1 months, median survival time was 12.8 months, and the median time to disease progression was 93 days. The most common treatment-related adverse events were hand-foot syndrome, diarrhea, nausea, vomiting, and fatigue. Diarrhea (14%) and hand-foot syndrome (10%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity in more than 10% of patients. Capecitabine is an active drug in the treatment of paclitaxel-refractory metastatic breast cancer. It has a favorable toxicity profile with the added advantage of being an oral drug administered at home.


Direct Imaging of Isolated Single-Molecule Magnets in Metal-Organic Frameworks.
Practical applications involving the magnetic bistability of single-molecule magnets (SMMs) for next-generation computer technologies require nanostructuring, organization, and protection of nanoscale materials in two- or three-dimensional networks, to enable read-and-write processes. Owing to their porous nature and structural long-range order, metal-organic frameworks (MOFs) have been proposed as hosts to facilitate these efforts. Although probing the channels of MOF composites using indirect methods is well established, the use of direct methods to elucidate fundamental structural information is still lacking. Herein we report the direct imaging of SMMs encapsulated in a mesoporous MOF matrix using high-resolution transmission electron microscopy. These images deliver, for the first time, direct and unambiguous evidence to support the adsorption of molecular guests within the porous host. Bulk magnetic measurements further support the successful nanostructuring of SMMs. The preparation of the first magnetic composite thin films of this kind furthers the development of molecular spintronics.


The influence of surfactant and solution composition on PFAS adsorption at fluid-fluid interfaces.
The objective of this research is to examine the influence of surfactant and solution composition on PFAS adsorption at fluid-fluid interfaces. Surface tensions were measured for select PFAS, as well as a representative hydrocarbon surfactant. These data are supplemented with data sets collected from the literature. The influence of surfactant headgroup charge, specifically for zwitterionic PFAS, was investigated. The impacts of surfactant counterion for ionic PFAS and the influence of headgroup size for nonionic PFAS were also investigated. In addition, the influence of solution ion composition, ionic strength, and pH was examined. The impact of co-solutes, specifically ethanol, humic acid, and trichloroethene, was also examined, as well as the behavior of PFAS mixtures and fluorocarbon-hydrocarbon surfactant mixtures. The data were interpreted within the framework of a QSPR model recently developed to predict fluid-fluid interfacial adsorption coefficients (Ki) of PFAS. The results demonstrate that all of the factors investigated have some degree of impact on Ki values. Thus, the composition of soil-pore water and groundwater is likely to affect the magnitude of PFAS adsorption at air-water and organic liquid-water interfaces. However, the influence on Ki of most of the factors investigated is small for lower PFAS concentrations (less than ∼1-10 mg/L). Hence, their impacts on fluid-fluid interfacial adsorption are likely to be relatively minor at the low PFAS concentrations representative of many environmental systems, especially compared to the impact of other factors such as fluid saturations, porous-medium properties, and PFAS molecular structure. The results of this study indicate that the revised QSPR model provides reasonable first-order predictions of Ki for a wide range of PFAS in environmental systems.


Baseline Patient Characteristics Commonly Captured Before Surgery Do Not Accurately Predict Long-Term Outcomes of Lumbar Microdiscectomy Followed by Physiotherapy.
Prospective cohort study. To develop and internally validate prognostic models based on commonly collected preoperative data for good and poor outcomes of lumbar microdiscectomy followed by physiotherapy. Lumbar microdiscectomy followed by physiotherapy is a common intervention for lumbar radiculopathy. Postoperatively, a considerable percentage of people continues to experience pain and disability. Prognostic models for recovery are scarce. We included 298 patients with lumbar radiculopathy who underwent microdiscectomy followed by physiotherapy. Primary outcomes were recovery and secondary outcomes were pain and disability at 12 months follow-up. Potential prognostic factors were selected from sociodemographic and biomedical data commonly captured preoperatively. The association between baseline characteristics and outcomes was evaluated using multivariable logistic regression analyses. At 12 months follow-up, 75.8% of the participants met the criterion for recovery. Variables in the model for good recovery included: younger age, leg pain greater than back pain, high level of disability, and a disc herniation at another level than L3-L4. The model for poor recovery included: lower educational level, prior back surgery, and disc herniation at L3-L4. Following internal validation, the explained variance (Nagelkerke R) and area under the curve for both models were poor (≤0.02 and ≤0.60, respectively). The discriminative ability of the models for disability and pain were also poor. The outcome of microdiscectomy followed by postoperative physiotherapy cannot be predicted accurately by commonly captured preoperative sociodemographic and biomedical factors. The potential value of other biomedical, personal, and external factors should be further investigated. 3.


Achieving rational design of alloy catalysts using a descriptor based on a quantitative structure-energy equation.
An approach to rationally design optimal alloy catalysts is established using nitric oxide (NO) oxidation as an example. We introduce a quantitative structure-energy equation to predict the chemisorption energies of adsorbates on alloy catalysts. The structure-energy descriptor is used to rationally design Pt-based and Ni-based alloy catalysts for NO oxidation. Full first principles calculations with kinetic simulations demonstrate that these designed catalysts possess much better catalytic performances than the traditional catalysts.


Maternal HIV Status and Risk of Infant Mycobacterium Tuberculosis Infection as Measured by Tuberculin Skin Test.
The effect of maternal HIV on infant Mycobacterium tuberculosis (Mtb) infection risk is not well-characterized. Pregnant women with/without HIV and their infants were enrolled in a longitudinal cohort in Kenya. Mothers had interferon gamma-release assays (QFT-Plus) and tuberculin skin tests (TST) at enrollment in pregnancy; children underwent TST at 12 and 24 months of age. We estimated the incidence and correlates of infant TST-positivity using Cox proportional hazards regression. Among 322 infants, 170 (53%) were HIV-exposed and 152 (47%) were HIV-unexposed. Median enrollment age was 6.6 weeks [interquartile range (IQR): 6.1-10.0]; most received Bacillus Calmette-Guerin (320, 99%). Thirty-nine (12%) mothers were TST-positive; 102 (32%) were QFT-Plus-positive. Among HIV-exposed infants, 154 (95%) received antiretrovirals for HIV prevention and 141 (83%) of their mothers ever received isoniazid preventive therapy (IPT). Cumulative 24-month infant Mtb infection incidence was 3.6/100 person-years (PY) [95% confidence interval (CI): 2.4-5.5/100 PY]; 5.4/100 PY in HIV-exposed infants (10%, 17/170) versus 1.7/100 PY in HIV-unexposed infants (3.3%, 5/152) [hazard ratio (HR): 3.1 (95% CI: 1.2-8.5)]. More TST conversions occurred in the first versus second year of life [5.8 vs. 2.0/100 PY; HR: 2.9 (95% CI: 1.0-10.1)]. Infant TST-positivity was associated with maternal TST-positivity [HR: 2.9 (95% CI: 1.1-7.4)], but not QFT-Plus-positivity. Among HIV-exposed children, Mtb infection incidence was similar regardless of maternal IPT. Mtb infection incidence (by TST) by 24 months of age was ~3-fold higher among HIV-exposed children, despite high maternal IPT uptake. Overall, more TST conversions occurred in the first 12 months compared to 12-24 months of age, similar in both HIV-exposed and HIV-unexposed children.


Clinical Decision-Making Following Disasters: Efficient Identification of PTSD Risk in Adolescents.
The present study aimed to utilize a Receiver Operating Characteristic (ROC) approach in order to improve clinical decision-making for adolescents at risk for the development of psychopathology in the aftermath of a natural disaster. Specifically we assessed theoretically-driven individual, interpersonal, and event-related vulnerability factors to determine which indices were most accurate in forecasting PTSD. Furthermore, we aimed to translate these etiological findings by identifying clinical cut-off recommendations for relevant vulnerability factors. Our study consisted of structured phone-based clinical interviews with 2000 adolescent-parent dyads living within a 5-mile radius of tornados that devastated Joplin, MO, and northern Alabama in Spring 2011. Demographics, tornado incident characteristics, prior trauma, mental health, and family support and conflict were assessed. A subset of youth completed two behavioral assessment tasks online to assess distress tolerance and risk-taking behavior. ROC analyses indicated four variables that significantly improved PTSD diagnostic efficiency: Lifetime depression (AUC = .90), trauma history (AUC = .76), social support (AUC = .70), and family conflict (AUC = .72). Youth were 2-3 times more likely to have PTSD if they had elevated scores on any of these variables. Of note, event-related characteristics (e.g., property damage) were not related to PTSD diagnostic status. The present study adds to the literature by making specific recommendations for empirically-based, efficient disaster-related PTSD assessment for adolescents following a natural disaster. Implications for practice and future trauma-related developmental psychopathology research are discussed.


Torsional eye movements in patients with skew deviation and spasmodic torticollis: responses to static and dynamic head roll.
We measured torsional eye movements induced by sinusoidal rotation or static tilt, of the head in roll while viewing a far or near target in 4 patients with skew deviation due to brainstem lesions, 4 patients with spasmodic torticollis (ST), 2 patients with unilateral eighth nerve section (VIIIS), and 10 normal subjects. Torsional nystagmus was present in all 4 patients with skew deviation. In subjects and patients, responses to both sinusoidal and static roll were larger while viewing the far target, consistent with factors dictated by geometry. Response gains to sinusoidal roll were abnormal in 3 patients with skew (increased in one, decreased in two), abnormal in 3 with ST (increased in 1, decreased in 2), and in abnormal both VIIIS patients (decreased). Greater abnormalities were evident in 3 skew patients while rolling away from the side of their brainstem lesions and in both VIIIS patients while rolling toward their lesioned ears. There were similar but less pronounced changes during static head roll. We conclude that patients with skew, ST, and VIIIS may all have abnormal ocular counter-rolling that is more evident during dynamic testing while viewing a far target. Such abnormalities endure because of the limited influence exerted by vision on torsional eye movements.


Well-differentiated biphasic synovial sarcoma in the atlanto-occipital joint of a Holstein cow.
A 7-year-old Holstein cow developed a large cystic mass in the region between the atlantoaxis and larynx. The mass extended to the synovium in the atlanto-occipital joint. Many villous projections were present on the inner surface of the tumor tissue, and irregular clefts were formed in the inside. Two cell types, epithelioid-like synovioblasts and spindle cells, were present. Immunohistochemical analysis showed that the cells stained positively for cytokeratin (AE1/AE3) and vimentin. Both cells had similar fine structures ultra-structurally. Vacuoles present in the cytoplasm were full of an acid mucous substance. The tumor was diagnosed as a well-differentiated biphasic synovial sarcoma. This is the first report of a rare case of synovial sarcoma, from the viewpoint of its origin.


Bayesian multichannel image restoration using compound Gauss-Markov random fields.
In this paper, we develop a multichannel image restoration algorithm using compound Gauss-Markov random fields (CGMRF) models. The line process in the CGMRF allows the channels to share important information regarding the objects present in the scene. In order to estimate the underlying multichannel image, two new iterative algorithms are presented and their convergence is established. They can be considered as extensions of the classical simulated annealing and iterative conditional methods. Experimental results with color images demonstrate the effectiveness of the proposed approaches.


Biochemical characterization of the ctr mutants of Escherichia coli.
A test procedure based on complementation in mixed extracts is described for the assay of heat-stable protein and enzyme I of the phosphoenolpyruvate-dependent phosphotransferase system. The test was used to assay a collection of pleiotropic carbohydrate mutants of Escherichia coli (ctr mutants) and revertants of these mutants. All mutants were found to lack enzyme I of the phosphoenolpyruvate-dependent transferase system. Revertants of these mutants to complete wild phenotype regained enzyme I-forming ability. Reversion to partial wild type was not accompanied by restoration of enzyme I-forming ability.


Non-uniform Label Smoothing for Diabetic Retinopathy Grading from Retinal Fundus Images with Deep Neural Networks.
Introducing a new technique to improve deep learning (DL) models designed for automatic grading of diabetic retinopathy (DR) from retinal fundus images by enhancing predictions' consistency. A convolutional neural network (CNN) was optimized in three different manners to predict DR grade from eye fundus images. The optimization criteria were (1) the standard cross-entropy (CE) loss; (2) CE supplemented with label smoothing (LS), a regularization approach widely employed in computer vision tasks; and (3) our proposed non-uniform label smoothing (N-ULS), a modification of LS that models the underlying structure of expert annotations. Performance was measured in terms of quadratic-weighted κ score (quad-κ) and average area under the receiver operating curve (AUROC), as well as with suitable metrics for analyzing diagnostic consistency, like weighted precision, recall, and F1 score, or Matthews correlation coefficient. While LS generally harmed the performance of the CNN, N-ULS statistically significantly improved performance with respect to CE in terms quad-κ score (73.17 vs. 77.69, P < 0.025), without any performance decrease in average AUROC. N-ULS achieved this while simultaneously increasing performance for all other analyzed metrics. For extending standard modeling approaches from DR detection to the more complex task of DR grading, it is essential to consider the underlying structure of expert annotations. The approach introduced in this article can be easily implemented in conjunction with deep neural networks to increase their consistency without sacrificing per-class performance. A straightforward modification of current standard training practices of CNNs can substantially improve consistency in DR grading, better modeling expert annotations and human variability.


N of 1 trials and the optimal individualisation of drug treatments: a systematic review protocol.
Guidelines and evidence-based drug treatment recommendations are usually based on the results of clinical trials, which have limited generalisability in routine clinical settings due to their restrictive eligibility criteria. These trials are also conducted in ideal and rigorously controlled settings. N of 1 trials, which are single patient multiple crossover studies, offer a means of increasing the evidence base and individualising care for individuals in clinical practice. This systematic review of the N of 1 drug treatment trial aims to investigate its usefulness for achieving optimal individualised patient care. The following databases will be searched for relevant articles: MEDLINE, EMBASE, PsycINFO (all via Ovid), AMED, CINAHAL (via EBSCO), The Cochrane Library (including CENTRAL, NHS EED, and DARE), and Web of Science (Thomson Reuters). Supplementary searches will include ongoing trial databases and organisational websites. All N of 1 trials in which patients have been treated with a drug will be considered. Outcomes will include information on the clinical usefulness of N of 1 trials-i.e. achievement of optimal individualised care, health-care utilisation of patients, frequently used practices, experiences of clinical care or participation in N of 1 trials, adherence to treatment plan, and unwanted effects of the treatment. Screening of included papers will be undertaken independently by two reviewers, while data extraction and the quality of reporting will be conducted by one reviewer and checked by another. Both quantitative and qualitative summaries will be reported using appropriate methods. This review will provide new insights into the clinical utility of N of 1 drug trials in helping participants find the most acceptable treatment as defined by patients and clinicians based on the selected outcome measures and the perspectives of participants involved in such trials. Findings from this review will inform the development of a stakeholder workshop and guidance to help physicians find the optimum therapy for their patients and will help guide future research on N of 1 trials. PROSPERO CRD42016032452.


Molecular phyloecology suggests a trophic shift concurrent with the evolution of the first birds.
Birds are characterized by evolutionary specializations of both locomotion (e.g., flapping flight) and digestive system (toothless, crop, and gizzard), while the potential selection pressures responsible for these evolutionary specializations remain unclear. Here we used a recently developed molecular phyloecological method to reconstruct the diets of the ancestral archosaur and of the common ancestor of living birds (CALB). Our results suggest a trophic shift from carnivory to herbivory (fruit, seed, and/or nut eater) at the archosaur-to-bird transition. The evolutionary shift of the CALB to herbivory may have essentially made them become a low-level consumer and, consequently, subject to relatively high predation risk from potential predators such as gliding non-avian maniraptorans, from which birds descended. Under the relatively high predation pressure, ancestral birds with gliding capability may have then evolved not only flapping flight as a possible anti-predator strategy against gliding predatory non-avian maniraptorans but also the specialized digestive system as an evolutionary tradeoff of maximizing foraging efficiency and minimizing predation risk. Our results suggest that the powered flight and specialized digestive system of birds may have evolved as a result of their tropic shift-associated predation pressure.


Pathophysiology of anemia in chronic kidney diseases: A review.
Backgroud. Anemia is one of the laboratory and clinical findings of chronic kidney diseases (CKD). The presence of anemia in patients with CKD has a wide range of clinically important consequences. Some of the symptoms that were previously attributed to reduced renal function are, in fact, a consequence of anemia. Anemia contributes to increased cardiac output, the development of left ventricular hypertrophy, angina, and congestive heart failure. According to current knowledge, anemia also contributes to the progression of CKD and is one of the factors that contribute to the high morbidity and mortality in patients with chronic renal failure and their reduced survival. MEDLINE search was performed to collect both original and review articles addressing anemia in CKD, pathophysiology of renal anemia, erythropoiesis, erythropoietin, iron metabolism, inflammation, malnutrition, drugs, renal replacement therapy and anemia management The present review summarized current knowledge in the field of the pathophysiology of renel anemia. Understanding the pathophysiology of anemia in CKD is crucial for the optimal treatment of anemia according to recent clinical practice guidelines and recommendation, and correct recognition of causes of resistence to treatment of erythropoietin stimulating agents (ESA).


Growing up aspen: ontogeny and trade-offs shape growth, defence and reproduction in a foundation species.
Intraspecific variation in foundation species of forest ecosystems can shape community and ecosystem properties, particularly when that variation has a genetic basis. Traits mediating interactions with other species are predicted by simple allocation models to follow ontogenetic patterns that are rarely studied in trees. The aim of this research was to identify the roles of genotype, ontogeny and genotypic trade-offs shaping growth, defence and reproduction in aspen. We established a common garden replicating >500 aspen genets in Wisconsin, USA. Trees were measured through the juvenile period into the onset of reproduction, for growth, defence chemistry (phenolic glycosides and condensed tannins), nitrogen, extrafloral nectaries, leaf morphology (specific leaf area), flower production and foliar herbivory and disease. We also assayed the TOZ19 sex marker and heterozygosity at ten microsatellite loci. We found high levels of genotypic variation for all traits, and high heritabilities for both the traits and their ontogenetic trajectories. Ontogeny strongly shaped intraspecific variation, and trade-offs among growth, defence and reproduction supported some predictions while contradicting others. Both direct resistance (chemical defence) and indirect defence (extrafloral nectaries) declined during the juvenile stage, prior to the onset of reproduction. Reproduction was higher in trees that were larger, male and had higher individual heterozygosity. Growth was diminished by genotypic allocation to both direct and indirect defence as well as to reproduction, but we found no evidence of trade-offs between defence and reproduction. Key traits affecting the ecological communities of aspen have high levels of genotypic variation and heritability, strong patterns of ontogeny and clear trade-offs among growth, defence and reproduction. The architecture of aspen's community genetics - its ontogeny, trade-offs and especially its great variability - is shaped by both its broad range and the diverse community of associates, and in turn further fosters that diversity.