The patients were treated with a Children and Leukemia Group B induction regimen.

Results:

Among these patients, BCR-ABL fusion oncogene was present in 43 of 78 patients (55%). A statistically significant difference in BCR-ABL-positivity within three age groups (< 20 years, 20-50 years, > 50 years) was observed (P = 0.001). The median age was significantly higher in the BCR-ABL+ group (30 vs 19 years; P = 0.001). BCR-ABL+

patients were also characterized by higher median WBC counts (96 000/mu L vs 23 000//mu L, P = 0.002). Complete remission was achieved in 74% BCR-ABL- patients and 35% BCR-ABL+ patients (P = 0.001). Only 10% of BCR-ABL- patients achieved continued complete remission (CR). None of the BCR-ABL+ patients maintained a CR further to induction therapy. With the available therapeutic Selonsertib price protocol, the presence of a BCR-ABL fusion predicted a lower survival (P = 0.001).

Conclusion:

A high prevalence of BCR-ABL gene fusion was observed that appeared as a poor prognostic factor. Identification of this genetic entity at diagnosis is crucial for understanding the nature MK-8931 Neuronal Signaling inhibitor of adult ALL and for deciding optimal treatment.”
“Background: Currently less than 15% of children under five with fever receive recommended artemisinin-combination therapy (ACT), far short

of the Roll Back Malaria target of 80%. To understand why coverage remains low, it is necessary to examine the treatment pathway from a child getting fever to receiving appropriate treatment and to identify critical blockages. This paper presents the application of such a diagnostic approach to the coverage of prompt

and effective treatment of children with fever in rural Senegal.

Methods: A two-stage cluster sample household survey was conducted in August 2008 in Tambacounda, Senegal, to investigate treatment behaviour for children under five with fever in the previous two weeks. The treatment pathway was divided in to five key steps; the proportion of all febrile drug discovery children reaching each step was calculated. Results were stratified by sector of provider (public, community, and retail). Logistic regression was used to determine predictors of treatment seeking.

Results: Overall 61.6% (188) of caretakers sought any advice or treatment and 40.3% (123) sought any treatment promptly within 48 hours. Over 70% of children taken to any provider with fever did not receive an anti-malarial. The proportion of febrile children receiving ACT within 48 hours was 6.2% (19) from any source; inclusion of correct dose and duration reduced this to 1.3%. The proportion of febrile children receiving ACT within 48 hours (not including dose & duration) was 3.0% (9) from a public provider, 3.0% (9) from a community source and 0.3% (1) from the retail sector.

Emissions data reported by pharmaceutical installations were aggregated

into a pollution trend using an Environmental Emissions Index (EEI) based on Lifecycle Assessment methodologies. Complete sectoral emissions data from 2001 to 2007 were extrapolated back to 1995, based on available data. Production volume data were used to derive a sectoral production index, and determine ‘no-improvement’ emission trends, whilst questionnaire responses from 20 industry representatives were used to quantify Alisertib clinical trial the contribution of integrated licensing to emission avoidance relative to these trends. Between 2001 and 2007 there was a 40% absolute, reduction in direct pollution from 27 core installations, and 45% pollution avoidance relative to hypothetical ‘no-improvement’ pollution. It was estimated that environmental regulation avoided 20% of ‘no-improvement’ pollution, in addition to 25% avoidance under business-as-usual. For specific emissions, avoidance ranged from 14% and 30 kt a(-1) for CO(2) to 88% and 598 t a(-1) for SO(x). AZD0530 research buy Between 1995 and 2007, there was a 59% absolute reduction in direct pollution, and 76% pollution avoidance. Pollution avoidance was dominated by reductions in emissions of VOCs, SO(x) and NO(x) to air, and emissions of heavy metals to water. Pollution avoidance of 35% was attributed to integrated licensing, ranging from between 8% and 2.9 t a(-1) for phosphorus emissions to water to 49% and 3143 t a(-1)

for SO(x) emissions to air. Environmental regulation enforced through integrated licensing has been the major driver of substantial pollution avoidance achieved by Ireland’s pharmaceutical sector – through emission limit values associated with Fedratinib purchase Best Available Techniques, emissions monitoring and reporting requirements, and performance targets specified in environmental management plans. This compliant sector offers a positive, but not necessarily typical, case study of IPPC effectiveness. (C) 2009 Elsevier Ltd. All rights reserved.”
“Objective The purpose of this study is to quantify and compare the resting cortisol levels between aqueous

(Aq) and plasma of anesthetized hound dogs utilizing mass spectrometry.

Animals Nine hound breed dogs weighing between 20.8 and 29.2 kg ((x) over bar = 26.3 kg, SD +/- 2.6 kg) were utilized from a previous project.

Procedures All dogs underwent two anesthesia sessions to harvest Aq from each eye respectively. A paired blood sample was taken immediately after aqueous centesis. The Aq and plasma were analyzed for cortisol levels using mass spectrometry. Correlation of cortisol levels in dog serum and ocular fluid was determined with Sigma Stat using Pearson’s correlation analysis. The level of significance for correlation analysis was set at P < 0.05.

Results The plasma resting cortisol levels in the dog ranged from 3.59 to 89.35 nM (<(x)over bar> = 31.68 nM, SD +/- 28.53 nM), while the Aq cortisol levels ranged from 0.82 to 5.

It is found that the energy gaps and work functions of these small BNNTs are strongly dependent on their chirality and diameters. The small zigzag BNNTs become desirable semiconductors and have peculiar distribution of nearly free electron (NFE) states due to strong hybridization effect. When such a small BNNT is inserted in a larger one, the energy gap of the formed double-walled BNNT can be even much reduced due to the coupled effect of

wall buckling difference and interwall NFE-pi(*) hybridization.”
“Implantation failure in assisted reproduction is thought to be mainly due to impaired uterine receptivity. With click here normal uterine anatomy, changes in endocrine profile during ovarian stimulation and medical conditions of the mother (i.e. thrombophilia and abnormal check details immunological response) could result in a non-receptive endometrium. High oestradiol concentrations during ovarian stimulation lead to premature progesterone elevation, causing endometrial advancement and hampering implantation, which can be overcome by a freeze-all approach and embryo transfer in natural cycles or by milder stimulation protocols. Patients with recurrent implantation failure (RIF) should be tested for inherited

and acquired thrombophilias. Each patient should be individually assessed and counselled regarding therapy with low-molecular-weight heparin (LMWH). Empirical treatment with LMWH, aspirin or corticosteroids is not effective for women with RIF who have negative thrombophilic tests. If thrombophilic tests are normal, patients should be tested for immunological causes. If human leukocyte antigen dissimilarity is proven, treatment with intravenous immunoglobulin might be beneficial. Preliminary observational studies using intralipid infusion in the presence of increased natural killer cytotoxic activity

are interesting but the proposed rationale is controversial and randomized controlled trials are needed. Hysteroscopy and/ or endometrial scratching in the cycle preceding ovarian stimulation should become standard for patients with RIF. (C) 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“Purpose Normative data for WHOQOL-bref are scarce in the literature and unavailable in Latin selleck American countries. The main objective of this study was to provide normative scores of WHOQOL-bref in a general population sample in Brazil and to describe differences in mean scores according to some socio-demographic characteristics.

Methods WHOQOL-bref was applied to a randomly selected sample of the general population of Porto Alegre. Participants were literate people aged 20 to 64 years. The questionnaires were self-administered in the presence of an interviewer in the respondent’s home.

Results The response rate was 68%, and the final sample contained 751 respondents (38% men, 62% women).

(C) 2009 Society of Chemical Industry”
“Purpose: DUB inhibitor To report one of the largest series of clinical and

renal function outcomes of treated iatrogenic vascular lesions (IVL) after partial nephrectomy (PN). Angioembolization (AE) is the treatment of choice for patients with these lesions, but the additional renal injury conferred by this treatment has not been well described. Patients and Methods: Patients who underwent open, laparoscopic, or robot-assisted PN from 2002 to 2012 were identified and those with AE were selected. Patients’ charts were reviewed, and renal function was analyzed using estimated glomerular filtration rate (eGFR) and progression of chronic kidney disease (CKD) classification before and after PN and AE. Results: There were 849 patients who underwent PN and an IVL developed in 28 (3.3%). Twenty (71%) presented with gross hematuria at a mean of 10.27.7 days after PN and 8 (28%) needed transfusion. All patients had identifiable IVL at the time of selective AE,

and technical success was achieved in 24/28 (86%), although 4 needed subsequent additional AE. The paired decrease in eGFR check details after PN was significant (P<0.01), while the paired change in eGFR after AE was not with either short-term (2.8 days) or intermediate-term (362 days) follow-up (P=0.50). Four patients experienced transient worsening in CKD classification after AE, although three experienced CKD stage improvement. Conclusion: Selective AE for IVL after PN is safe, efficacious, and does not lead to a significant impairment of renal function. It remains the preferred approach for the evaluation and management of post-PN hemorrhage.”
“Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a major concern worldwide. In the United States, ST8 CA-MRSA with SCCmecIVa (USA300) has been predominant, affecting the entire United States. In this study, we investigated Japanese ST8 CA-MRSA with new SCCmecIVl (designated ST8 CA-MRSA/J), which

has emerged in Japan since 2003. Regarding community spread and infections, ST8 CA-MRSA/J spread in 16.2-34.4% as a major genotype in the https://www.sellecn.cn/products/entrectinib-rxdx-101.html community in Japan, and was associated with skin and soft tissue infections (SSTIs), colitis, and invasive infections (sepsis, epidural abscesses, and necrotizing pneumonia), including influenza prodrome cases and athlete infections, similar to USA300. It spread to even public transport and Hong Kong through a Japanese family. Regarding genetic diversity, ST8 CA-MRSA/J included ST and spa variants and was classified into at least three pulsed-field gel electrophoresis types, ST8 J alpha to gamma. Of those, ST8 J beta was associated with severe invasive infections. As for genomics, ST8 CA-MRSA/J showed high similarities to USA300, but with marked diversity in accessory genes; e.g.

Poverty and level of schooling were found as important determinants of malaria knowledge and practices. Allopathic treatment was uniformly advocated, but the ‘know-do’ gap became especially evident when in practice

majority of the ill persons either did not seek any treatment (31%) or practiced self-treatment (12%). Of those who sought treatment, the majority went to the village doctors and drugstore salespeople (around 40%). Also, there was a delay beyond twenty-four hours in beginning treatment of malaria-like fever in more than half of the instances. In the survey, gender divide in knowledge and health-seeking behaviour was observed disfavouring women. There was also a geographical divide between the high endemic south-eastern area and the low-endemicnorth-eastern area, the former being 17-AAG disadvantaged with respect to different aspects of malaria studied.

Conclusion: The respondents in this study lacked comprehensive knowledge on different

aspects of malaria, which was influenced by level of poverty and education. A gender and geographical divide in knowledge was observed disfavouring women and south-eastern area respectively. They preferred allopathic treatment for malaria, although a substantial proportion did not seek any treatment or sought self-treatment for malaria-like fever. Delay in seeking care was common. The implications of these findings for programme development are discussed.”
“Ramsay Hunt syndrome is defined as herpes zoster oticus associated with an acute peripheral facial nerve paresis and quite often with other cranial nerve

lesions. check details The combination of motor, sensory and autonomic involvement leads to a variety of neurological damage patterns, i.e. facial muscle paresis, hearing and balance disorders, sensory RG7440 problems and disturbances of taste as well as lacrimal and nasal secretion. Additional variability of the clinical picture of Ramsay Hunt syndrome is produced by varying patterns of skin involvement explained by individual anastomoses between cranial and cervical nerves. Knowledge of these findings and an early diagnosis of Ramsay Hunt syndrome are important as prognosis of cranial nerve damage depends on the time at which acyclovir-corticosteroid therapy is started.”
“Introduction: Short- and medium-term sinus rhythm (SR) rates after intraoperative radiofrequency ablation to treat permanent atrial fibrillation (AF) are well documented. Is rhythm success stable during a long-term follow-up?

Methods and Results: A total of 130 patients who had undergone intraoperative radiofrequency cooled-tip endocardial ablation (SICTRA) of permanent AF (mean AF duration 6 +/- 5 years) concomitant to open heart surgery more than 3 years ago were followed up using electrocardiogram (ECG), Holter-ECG, and echocardiography and compared with 12-month follow-up data. In 55% of patients, only the left atrium and in 45%, both atria were treated using SICTRA.

This variation presents challenges for clinicians to apply these data in clinical practice. Consistent reporting practices, which are interpretable by clinicians, are required, as are processes to achieve AZD1208 this consistency in future reports.”
“CePtSn belongs to the group of orthorhombic CeTX compounds. Similar to some other CeTX companions, it exhibits a pronounced anisotropy of electronic and elastic properties with respect to the direction of an applied magnetic field. We report on our study of the temperature and magnetic field evolution

of the thermal expansion and magnetostriction, acquiring all the major components of the corresponding tensors. Also, the evolution of the electrical resistivity across the H-T-p space was investigated in order to confirm and extend the information on physics of the studied material. We have observed a significant SCH772984 nmr dependence of elastic properties

on the magnetic history for the magnetic field applied along the b-axis, which is reflecting a nontrivial evolution of magnetic ordering. Consequently, these results are discussed within the framework of the appearance of magnetism in the Ce(Pt,Ni)Sn system and the relationship between the elastic properties and the results of the investigation of pressure induced effects. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3057929]“
“Methanol extract of Helichrysum foetidum Moench (Asteraceae) was investigated for antioxidative properties. The antioxidant activities were investigated by 2,2-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging, ss-carotene/linoleic acid assay, scavenging of hydrogen peroxide (HRPO test), superoxide anion scavenging (S.A.S. test) and hypochlorous acid scavenging (taurine test). The antioxidant activity was reported as IC50 and reveals Trolox-like antioxidative effects.”
“Propagation of phonon polaritons in a nonaxial aligned one-dimensional

piezoelectric superlattice is studied theoretically. Because of the piezoelectric effect, both transverse Screening Library high throughput and longitudinal superlattice vibrations are induced by one transverse polarized electromagnetic wave. Due to the coupling effect, two orthogonal modes of elliptically polarized polaritons are present with different propagation properties and can be tuned by the rotation angle. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3093682]“
“To assess how health-related quality of life (HRQoL) varies by body mass index (BMI) category among gender and racial subgroups using nine HRQoL measures.

Among 3,710 US adults, we evaluated self-reported height, weight, and HRQoL that was measured by six indexes (EQ-5D; HUI2; HUI3; SF-6D; QWB-SA; HALex) and three summary measures (theta; PCS; MCS). Mean HRQoL was estimated by weighted regression for normal, overweight, and obese subgroups (BMI: 18.5-24.

Subgroup analysis was used to clarify the effects of the techniques used (prelocation or guidance) or the experience of practitioners.

Results:

Literature found five articles. Most of the patients were cardiac surgery patients. In comparison with AL, UPG had no effect on IJV access failure rate (OR = 0.28 [0.05, 1.47], I superset of = 75%, P = 0.003), the rate of carotid artery puncture (OR = 0.32 [0.06, 1.62], I superset of = 68%, P = 0.01), haematoma, haemothorax, or pneumothorax

occurrence (OR = 0.40 [0.14, 1.13], AZD8055 cell line I superset of = 17%, P = 0.30, OR = 0.72, OR = 0.81 [0.18, 3.73], I superset of = 0%, P = 0.94, respectively) and time to IJV access and haemothorax/pneumothorax occurrence. Subgroup analysis found an efficacy of ultrasound when used by novice operators or during intraoperative use.

Discussion:

This current meta-analysis does not found the utility of ultrasound during IJV access in children Cyclosporin A in vitro and infants in increasing the success rate and in decreasing complications.”
“Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different

brain networks. Social defeat has been an important approach for understanding selleck chemicals neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories.

We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naive to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.”
“Background: Research shows that impairment in the expression and recognition of emotion exists in multiple psychiatric disorders.

The ovaries were divided into the experimental groups according to different perfusion pressure and different length of perfusion period. Follicular viability was assessed using the trypan blue test; the percentage of morphologically normal primordial follicles and the 17-beta estradiol level in the culture supernatants were measured.

When perfusion pressure was 100

mmHg, and the length of perfusion period was 40 min, the viability of ovarian tissues in bovine whole ovarian cryopreservation were higher than other protocols.

Protocol IIb (the perfusion pressure was 100 mmHg, and the length of perfusion G418 mouse period was 40 min) was appropriate for bovine whole ovarian cryopreservation.”
“This work examined the feasibility of using certain genes of carbon metabolism enzymes as molecular markers adequate for studying phylogeny and ecology of green sulfur bacteria (GSB) of the Chlorobi phylum. Primers designed

to amplify the genes of ATP citrate lyase (aclB) and citrate synthase (gltA) revealed the respective genes in the genomes of all of the newly studied GSB strains. The phylogenetic trees constructed buy Compound Library based on nucleotide sequences of these genes and amino acid sequences of the conceptually translated proteins were on the whole congruent with the 16S rRNA gene tree, with the single exception of GltA of Chloroherpeton thalassium, which formed a separate branch beyond the cluster comprised by other representatives of the Chlorobi phylum. Thus, the aclB genes but not gltA genes proved to be suitable for the design of primers specific to all Chlorobi representatives. Therefore, it was the aclB gene that was further used as a molecular marker to detect GSB in enrichment cultures and environmental samples. AclB phylotypes of GSB were revealed in all of the samples studied, with the exception of

environmental samples from soda lakes. The identification of the revealed phylotypes was in agreement with the identification Kinase inhibitor Library ���� based on the FMO protein gene (fmo), which is a well-known Chlorobi-specific molecular marker.”
“A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: in patients with hypertrophic and keloid scarring of the sternotomy wound, is surgical excision with or without adjuvant treatment of any benefit in reducing the size of the scar? Altogether, more than 15 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. One of the studies showed no difference between surgery and adjunctive triamcinolone or colchicine. One study showed that incomplete excision resulted in higher recurrence rates.

The level of tartrate-resistant acid phosphatase 5b as a marker of bone resorption in mice administered both LPS and anti-c-Fms antibody was also lower. Furthermore, the expression of the receptor activator of necrosis factor-kB, which is receptor activator of nuclear factor

kappa-B ligand, was increased upon LPS administration, but the expression was inhibited by anti-c-Fms antibody. These results showed that anti-c-Fms antibody inhibits LPS-induced osteoclast formation. In conclusion, M-CSF and its receptor are potential therapeutic targets in bacterial infection-induced osteoclastogenesis, and anti-c-Fms antibody might be useful for inhibition of bacterial infection-induced bone destruction.”
“To investigate the effect of pre-pregnancy BMI on adverse MK-8776 cost maternal and neonatal outcomes in pregnancy women of northern China.

We conducted a retrospective population-based cohort study of 5,047 singleton nulliparous pregnancies. The subjects

were categorized into four groups by BMI-underweight (BMI < 18.5 kg/m(2)), normal (BMI 18.5-24 kg/m(2)), overweight (BMI 24-28 kg/m(2)) and obese (BMI a parts per thousand yen 28 kg/m(2)). Logistic regression was used to adjust the potential confounder. Maternal and neonatal outcomes were evaluated with relative risks and 95% confidence intervals.

11.5, 63.4, 18.3, and 6.8% of the subjects were underweight, normal BMI, overweight and obese, 4SC-202 mouse respectively. Compared with women of normal BMI, the risk of the following outcomes was significantly EPZ004777 nmr increased in overweight and obese women and expressed as [adjusted RR (95% confidence interval)] respectively: pre-eclampsia [2.99 (2.21-4.06), 5.68 (3.97-8.11)]; gestational diabetes [2.49 (1.82-3.39), 4.35 (3.00-6.31)]; premature rupture

of the membranes [1.64 (1.20-2.23), 1.73 (1.11-2.72)]; abruption placentae [1.84 (1.19-2.87), 2.79 (1.60-4.83)]; cesarian section [1.47 (1.27-1.70), 2.51 (1.97-3.20)]; postpartum hemorrhage [2.31 (1.51-3.54), 3.73 (2.37-5.04)]; perineal rupture [2.89 (1.44-5.81), 3.36 (1.55-7.30)]; large-for-gestational age [1.46 (1.02-2.08), 1.91 (1.17-3.10)]. However, anemia (2.54, 1.15-5.63), small-for-gestational age (1.67, 1.07-2.61) were significantly more common in the underweight group.

The prevalence of overweight and obesity in women of northern China is much lower than in the Caucasian population or Chinese in Hong Kong. The increased maternal BMI is associated with many adverse pregnancy outcomes and its risk increases with the degree of obesity. Maternal underweight has a protective effect although increases the risk of having small-for-gestational age baby and anemia.”
“Background. Pneumoperitoneum (P) created to facilitate laparoscopy (L) is associated with splanchnic hypoperfusion, ischemia/reperfusion (I/R) injury, and oxidative stress. Aim.

“
“Background: The recent growth in methamphetamine use internationally has raised concerns about the relationship between methamphetamine use and HIV infection. However, the risks associated with

methamphetamine injection have not been fully described, particularly outside of Western countries. Therefore, we sought to examine the relationship between methamphetamine injection and syringe sharing among injection drug users (IDU) in Bangkok, Thailand.

Methods: Using bivariate statistics and multivariate logistic regression, we examined the prevalence of methamphetamine 4SC-202 nmr injection and the relationship between more than weekly methamphetamine injection and syringe sharing among a community-recruited sample of IDU participating 3-MA in the Mitsampan Community Research Project in Bangkok.

Results: During June and July 2009, 311 IDU participated in this study, including 91(29.3%) women. In total, 114 (36.7%) participants reported having injected methamphetamine (“”yaba”") twice or more per week in the past six months. In multivariate analyses,

after adjustment for potential social, demographic and behavioral confounders, syringe sharing remained independently associated with injecting methamphetamine more than once per week (adjusted odds ratio = 2.86, 95% confidence interval: 1.59-5.15).

Conclusions: Over one-third of a community-recruited sample of Thai IDU reported more than weekly injection of methamphetamine, and methamphetamine injection was independently associated with syringe sharing. Essential HIV prevention services targeting IDU, such as syringe exchange and evidence-based addiction treatment, should be included in interventional efforts to address methamphetamine use in Thailand. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Cardiovascular disease is the leading cause of death amongst patients with chronic kidney disease, particularly end-stage disease. Patients

with chronic kidney disease commonly exhibit abnormalities of lipid profile, but also atypical cardiovascular risk Screening Library concentration factors such as arterial stiffness and chronic inflammation. Hence it is unclear whether these patients benefit from lipid-lowering therapy to the same degree as the general population. In this review we discuss evidence on the clinical benefit and safety of lipid-lowering agents for different stages of chronic kidney disease.”
“Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S.