Abstract Failure of passive transfer (FPT) of immunoglobulins (IgG) is associated with increased morbidity and mortality of calves. In this study we evaluated the digital Brix refractometer usefulness for the assessment of FPT. A number of 16 colostrum samples from the first milking (2-3h post-partum) of Holstein-Friesian dairy heifers and 29 blood sera of 3-6 days old calves were analyzed with a digital Brix refractometer. Total proteins were determined by the biuret reaction. Colostral IgG were determined by radial immunodiffusion (RID), and colostral whey and blood serum γ globulin (composed almost entirely of IgG) were determined by agarose protein gel electrophoresis (APE) and densitometry. Colostral % Brix score was 25.5±3.4%. Concentrations of colostrum IgG and colostral whey γ globulin were 130±33 g/L and 100±24 g/L respectively. The concentration of total proteins in colostral whey was 134±30 g/L. The correlations between Brix values and the concentrations of IgG determined with RID and the concentrations of γ globulin determined with APE were positive and highly significant (P<0.001 and P<0.01). The concentration of serum proteins of new-born calves was 57.75±11.8 g/L, the concentration of γ globulin was 14.4±7.8 g/L, and the Brix score was 8.6±1.0%. FPT (serum γ globulin<10 g/L) was detected in 34.5% (10/29) calves. Brix score correlated with the concentration of blood serum γ globulins in all examined calves. The results have confirmed that digital Brix refractometry allows the producers to use this technique in order to estimate colostral and calf serum IgG, thereby monitoring both colostrum quality and success of passive transfer.


The aggregation morphologies of conjugated polymers in solutions and solid films are important for their optoelectronic applications. Due to the amorphous state of the polymers, it remains a great challenge to determine their conformations in either liquids or solids. Herein, a ps/fs synchronized 2D IR technique is applied to investigate the molecular conformations of a high-mobility n-type low-bandgap copolymer, N2200, dissolved in CHCl3 and CCl4, and in solid films cast from both solutions by the vibrational cross-angle method. In CCl4, the polymer forms more aggregates and folds more and the backbone dihedral angle of C-C(NDI)/C-S(Thiophene) of its average conformation is about 10° more distorted than that in CHCl3 and the most stable conformation for a free molecule. Anti-intuitively, the solid films cast from both solutions have the same molecular conformation, and the conformation is similar to that of the polar CHCl3 rather than the conformation of the less polar CCl4. The results imply that the interaction between the polymer backbones is probably stronger than its interaction with CCl4, which can naturally guide the rearrangement of polymer chains during the evaporation of solvent molecules. This work also implies that the balance and competition between the polymer/polymer interaction and the polymer/solvent interaction seem to be the dominant factors responsible for what morphology can form in a solid film cast from solution. It is not always true that different molecular conformations must exist in solid films grown from different solutions with different polarity or different extents of aggregates with different conformations.


Using self-report survey methodology, this article examines the relationship between gender and police officers'perceptions of their job performance. Based on surveys of 217 male and female officers, results show that male and female officers perceive themselves equally qualified to carry out tasks required in law enforcement, including administration and supervision. This research suggests that male and female police officers work equally well on their jobs and there are no significant differences in their job performance, capabilities, and administration skills even when level of education and years of experience are controlled.


Energy conversion phase-change materials (PCMs) have recently attracted increasing attention in thermal energy storage applications. In particular, integrating PCMs with carbon scaffolds can effectively enable the stimulus-responsive latent heat storage and improve the shape stability of PCMs. In this work, we fabricated a conductive 3D reduced graphene/carbon scaffold (GPC) via the carbonization of graphene oxide (GO) doped cellulose acetate fiber scaffolds derived from waste cigarette filters. The GO coating preserved the structural integrity and enhanced the conductivity of the carbonized scaffold. The mesoporous characteristics of the GPC scaffold provided a good encapsulation efficiency of paraffin wax (PW) with leakage-proof performance during the phase-change process. The GPC, with a high conductivity of approximately 294.9 S m−1, offered excellent electrothermal conversion and storage efficiency of about 88% for the GPC–PW composite. The PCM composite was also an energy-efficient electrothermal storage material that releases heat more steadily and improves the thermal management function compared with its counter-part GPC scaffold. Thus, GPC fabrication paves a new path toward the sustainable and eco-friendly production of energy conversion supports for practical applications of PCM based thermal energy storage and thermal management devices.


Abstract High-precision 14 N NMR shieldings are reported for all of the possible N -methyl triazoles in a variety of solvents. A large difference is observed in the effects of solvent on the shieldings of the pyrrole-type and pyridine-type nitrogen atoms in such systems. This difference largely arises from solvent-to-solute hydrogen-bonding effects for the latter type of nitrogen atom. For these two types of nitrogen atoms in triazoles, solvent polarity effects induce changes in the shieldings in opposite directions: this is corroborated by shielding calculations using the solvaton model. Solvent-to-solute hydrogen-bonding effects are larger than those due to solvent polarity and permit the assessment of the basicities of nonequivalent nitrogenous sites; these appear to parallel the analogous basicities with respect to protonation.


ZnO/ZnCo2O4 tube in tube nanostructures were successfully fabricated by single capillary electrospinning technology and calcination treatment. The tube in tube nanostructure was achieved via adjustment of the heating ratio during the calcination process. The composition and nanostructure of ZnO/ZnCo2O4 tube in tube were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high resolution transmission microscopy (HRTEM), Brunauer–Emmett–Teller (BET), and X-ray photoelectron spectroscopy (XPS). Excellent gas sensing performance of the structure was observed, with high response (58) of as-prepared material toward 100 ppm ethanol vapor at an optimal temperature of 150 °C. Rapid response time (5.6 s) and recovery time (4.8 s) were recorded at this optimal temperature. Noticeable response (13) was also observed of 100 ppm ethanol vapor at 75 °C. The tube in tube nanostructure, n–p heterojunction, and oxygen vacancies are potential reasons for the excellent gas sensing performance. The sensing mechanism of the as-prepared ZnO/ZnCo2O4 n–p heterostructure toward ethanol vapor was discussed.


The instantaneous unit hydrograph (IUH) is a commonly used method for computing surface runoff hydrographs from small watersheds. Assuming travel time as a random variable, a general equation for IUH is derived using the entropy theory. This equation specializes into several well-known equations, such as the gamma distribution, Lienhard distribution, and Nakagami-m distribution, to name but a few. The general equation has three parameters, two of which are based on specified information (or constraints) on travel time, and the third parameter is an exponent that can also be determined from the specified values of travel time. In this study, the derived equation is tested on two small agricultural experimental watersheds. Surface runoff hydrographs computed using the derived IUH equation are found to be in satisfactory agreement with observed surface runoff hydrographs.


The supply planning of assembly systems under lead time uncertainty is studied. The used criteria is the sum of the average holding cost for the components, the average backlogging cost for the finished product, and the setup cost. The studied policy avoids the nervousness and the decision variables are the planned lead times of components, and the periodicity of the periodic ordering quantity method is also a decision variable. A mathematical method that gives the optimal values for these parameters is given.


Mutation in Werner (WRN) RECQL helicase is associated with premature aging syndrome (Werner syndrome, WS) and predisposition to multiple cancers. In patients with solid cancers, deficiency of the WRN RECQL helicase is paradoxically associated with enhanced overall survival in response to treatment with TOP1 inhibitors, which stabilize pathological TOP1‐DNA‐covalent‐complexes (TOP1cc) on the genome. However, the underlying mechanism of WRN in development of chemoresistance to TOP1 inhibitors is not yet explored. Our whole‐genome transcriptomic analysis for ~25,000 genes showed robust activation of NF‐κB‐dependent prosurvival genes in response to TOP1cc. CRISPR‐Cas9 knockout, shRNA silencing, and under‐expression of WRN confer high‐sensitivity of multiple cancers to TOP1 inhibitor. We demonstrated that WRN orchestrates TOP1cc repair through proteasome‐dependent and proteasome‐independent process, unleashing robust ssDNA generation. This in turn ensues signal transduction for CHK1 mediated NF‐κB‐activation through IκBα‐degradation and nuclear localization of p65 protein. Intriguingly, our site‐directed mutagenesis and rescue experiments revealed that neither RECQL‐helicase nor DNA‐exonuclease enzyme activity of WRN (WRNE84A, WRNK577M, and WRNE84A‐K577M) were required for TOP1cc removal, ssDNA generation and signaling for NF‐κB activation. In correlation with patient data and above results, the TOP1 inhibitor‐based targeted therapy showed that WRN‐deficient melanoma tumors were highly sensitive to TOP1 inhibition in preclinical in vivo mouse model. Collectively, our findings identify hitherto unknown non‐enzymatic role of WRN RECQL helicase in pathological mechanisms underlying TOP1cc processing and subsequent NF‐κB‐activation, offering a potential targeted therapy for WRN‐deficient cancer patients.


The recurring, widespread and sudden nature of fire and floods disasters pose high degree of risks frequently in secondary schools. However, the capacity of the affected secondary schools is limited due to paucity of student's disaster risk reduction awareness. The study endeavoured to assess the level of student disaster risk reduction awareness in secondary schools in Kisumu County. The study grounded on Planned Behaviour and Disaster Preparedness theory while adopting a descriptive research design. A sample size of 86 out of 172 public secondary schools was used. All principals from sampled schools were selected. Also, 172 students comprising of 2 student leaders, one Head of Department from each selected schools were sampled totalling to 86, and 4 ministry of education officials from Kenya School of Curriculum Development were purposively sampled. Data was collected using questionnaires and observation schedule. Qualitative data collected was put under themes consistent with the research objective. Quantitative data was coded and entered in the computer for analysis using the Statistical Package for Social Sciences (SPSS) version 27. Descriptive statistics such as percentages, means and frequencies were used to analyse the data. The study revealed that there was no disaster risk reduction and resilience in current curricula in secondary school. Students lacked capacity to respond to disasters in secondary schools in Kisumu County since they lacked disaster management training. The study recommends formulation of effective and practical disaster syllabi, alongside specialized training for teachers who would be delivering DRR education which builds on students' existing knowledge and experience by developing additional competencies needed for effective disaster management. Rehearsal drills in disaster preparedness must be done in secondary schools by students since it re-emphases points made in separate training programs and test the systems as a whole and invariably revealing several gaps that otherwise might have been overlooked.


In Reply. —Drs Tornambe and Poliner raise interesting questions about the treatment strategy for NVMs within the foveal avascular zone. However, we do not believe that "treatment inside the foveal vascular zone remains a dilemma." Results in our initial report on the effectiveness of krypton laser photocoagulation in preventing loss of vision 1 showed that among eyes with neovascularization within 200 μm of the foveal center, 8% of treated eyes in comparison with 32% of untreated eyes had large losses in visual acuity (≥ 6 lines). While intentional partial treatment of the neovascularization to spare receptors within the foveal avascular zone is appealing, we have misgivings about the strategy. The proposed partial treatment is far less extensive than treatment applied to eyes that were not completely covered in the Krypton Ocular Histoplasmosis Study. Subsequent persistent leakage from the NVM and its vision-threatening effects may overwhelm the benefit of sparing some


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Illnesses occurring among people stayed in high mountain conditions are classified in four separated categories. Diseases connected with hypobaria and hypoxia, low temperature, as a result of solar radiation effect, and intensification health problems running until this time asymptomatically belong to them. Knowledge concerning existing threats, prevention, right diagnosis and treatment of illnesses have fundamental significance for success of every expedition or operation realized in high mountains as well as for health and life protection of its participants. This article presents a review of the most often diseases happened during the stay in high mountain environment on the ground of the world literature and own experience.


Objective: The study aimed to identify the effects of restless legs syndrome (RLS) on sleep quality and quality of life in pregnant women.Methods: This comparative and descriptive study was conducted with 109 pregnant women between the 24 and 39 weeks of gestation. The presence and severity of RLS were investigated using the International Restless Legs Syndrome Study Group's Diagnostic Criteria Scale and Severity Rating Scale, and the effects of the syndrome on sleep and quality of life were evaluated. Results: The prevalence of RLS in pregnant women was found to be 47.7%. In the RLS group, 22.0% of the pregnant women had severe RLS symptoms and 20.2% had moderate RLS symptoms. The mean score for Restless Legs Syndrome Severity Rating Scale was determined 20.75±6.38. The mean score for quality of life scale was determined 17.75±3.73 in RLS group and 26.46±2.67 in non-RLS group. Conclusion: The difference between the mean scores for Pittsburgh Sleep Quality Index of the pregnant women with RLS and those without the syndrome was found to be statistically significant. While the mean score for Quality of Life Scale in pregnant women with RLS was lower in general health, physical health and psychological health sub-dimensions, no statistically significant difference was found in social relations and environment sub-dimensions. It is recommended that nurses investigate RLS complaints of pregnant women and include non-pharmacological methods in their nursing practices.


Objective : This study aimed to determine the burden of oral health parameters such as dental caries, dental plaque, gingivitis, periodontitis, mouth opening, and dental fluorosis among children and early adolescents belonging to upper and lower-middle-class private schools of Karachi Methods : A cross-sectional study with 550 study subjects was conducted among schools to assess dental caries, the presence of dental plaque, gingivitis, dental fluorosis, and mouth opening. The sample was selected through a nonprobability sampling technique. The inclusion criteria were male and female students from class 6 to class 10, students present on the day of the examination, and students given verbal consent for the study; the exclusion criteria included students with dental anomalies such as amelogenesis imperfecta, dentinogenesis imperfecta, supernumerary teeth, congenitally absent teeth or teeth missing due to fracture or trauma. An open epi was used to calculate the sample size. The study was performed in private schools belonging to various localities near Ziaud-din University. Dental examination was carried out using a disposable dental examination kit. SPSS version 20 was used for data analysis, and the nonparametric Mann-Whitney test was used to analyse the variables. Results: The mean age of the study sample is 12.96 ± 2.30, the mean DMFT (Decayed missing and filled tooth) score is 1.07 ± 2.04, the mean plaque score is 0.38 ± 0.90, and the gingival index is 0.21 ± 0.79, the mean mouth opening is 36.16±8.65. The gender-wise distribution of oral health parameters presented the statistically significant difference in mean mouth opening among male and female study subjects p<0.0001, whereas mean decayed tooth and mean DMFT scores were statistically insignificant p<0.44 and p<0.36, respectively. The comparison of oral health parameters of study subjects among upper and lower class shows statistically significant differences among mean mouth opening, mean plaque index, mean decayed teeth, mean DMFT score, and mean dental fluorosis. Whereas the mean gingival index, mean missing teeth and mean filled teeth were statistically insignificant. Conclusion: The current study concludes that children and early adolescents suffer from oral diseases such as dental caries, plaque, and limited mouth opening. There is a need to conduct oral health intervention studies among schools and local communities to spread oral health awareness and disease prevention. As well as to introduce preventive measures among high-risk subjects.


The post-war ritual – a comparative analysis of the Danish war booty offerings and the Roman triumphsThis article is inspired by a theory, which postulates that the Roman triumphs should be seen as an inspirational source relative to the interpretation of war booty offerings found in Danish bogs, and aims to examine the validity of this claim. The so-called triumph theory originates in the discussion of whether the military equipment recovered from Danish bogs stems from defensive or offensive battles. According to the triumph theory, the war booty was brought home from battles fought in foreign parts by a victorious Germanic people. It was then was placed in a triumph procession, following the Roman model, with display of the booty, and finally sacrificed in a lake according to traditional Germanic custom.After a general introduction to the Roman triumphs (fig. 1) and the Danish war booty offerings (fig. 2), some of the elements making up these two ceremonies are presented, specifically the actual material war booty, the human captives and the animals (figs. 4-5). There are distinct differences between the two ceremonies, for example in the war booty included in the Roman triumphs (fig. 3) and the Germanic war booty offerings, respectively. One discrepancy, which is difficult to ignore, is the treatment of, and further potential for reuse of, the captured weapons of the enemy displayed in the two ceremonies. There are examples where booty from the Romans' triumphs was later reused. This could not be the case for the Germanic war booty offerings, whereby weapons underwent such a massive process of destruction and, furthermore, were then deposited in lakes, making reuse seem impossible.The locations where the respective ceremonies took place – the city of Rome and South Scandinavian lakes – are then presented.An alternative explanation for the war booty offerings is then examined. Instead of seeing them as a Germanic version of the Roman triumphs, could the offerings be interpreted as Roman victory trophies (fig. 6)? This idea is rejected due to the lack of evidence for the sites of the offerings also being that of the actual battle field.Finally, attention is turned to the classical writers, who wrote about the Germanic and Gallic custom of depositing of military equipment, in order to extract what they can say about the gods whom the two ceremonies were intended to benefit.In the conclusion, the arguments are summed up in support of the author's view that the triumph theory does not provide a convincing explanation for the Danish war booty offerings.Pernille Mosholm Boye ThulstrupForhistorisk ArkæologiInstitut for Kultur og SamfundAarhus Universitet


Cihunamides A-D (1-4), novel antibacterial RiPPs, were isolated from volcanic island-derived Streptomyces sp. The structures of 1-4 were elucidated by 1H, 13C, and 15N NMR, MS, and chemical derivatizations; they contain a tetrapeptide core composed of WNIW, cyclized by a unique C-N linkage between two Trp units. Genome mining of the producer strain revealed two biosynthetic genes encoding a cytochrome P450 enzyme and a precursor peptide. Heterologous co-expression of the core genes demonstrated the biosynthesis of cihunamides via a P450-mediated oxidative Trp-Trp crosslinking. Further bioinformatic analysis uncovered 252 homologous gene clusters, including that of tryptorubins, which possess a distinct Trp-Trp linkage. Cihunamides do not display non-canonical atropisomerism shown in tryptorubins, which are the founding members of the "atropitide" family. Therefore, we propose to use a new RiPP family name "bitryptides" for cihunamides, tryptorubins, and their congeners, wherein the Trp-Trp linkages define the structural class rather than non-canonical atropisomerism.


Adhesives for gastric hemorrhage are of great clinical significance. However, it remains a major challenge in clinics due to its poor stability under acidic environments and low adhesion to wet tissues. Herein, inspired by the high adhesiveness of the ascidian secretory protein, we designed a series of aciduric bionic hydrogel adhesives (PDTAs) based on poly(γ-glutamic acid) (γ-PGA) and tannic acid (TA). The formation of hydrogel adhesives was attributed to the abundant hydrogen bonds between amide groups of PGA-DA and polyphenol groups of TA. These hydrogel adhesives exhibited enhanced wet tissue adhesion (400%), higher stretchability (800% elongation), and aciduric stability (7 days) compared with commercial fibrin glue. Rodent wound models indicated that the hydrogel adhesives demonstrated significant healing promotion due to ameliorating collagen deposition and angiogenesis. These hydrogel adhesives show great potential in treating gastric hemorrhages and promoting wound healing.


Two structurally interesting 3,6-dinitropyrazolo[4,3-c]pyrazole-based energetic cocrystals were prepared and confirmed by single crystal X-ray diffraction. As novel energetic materials, these two unusual neutral acid-base complexes possess high nitrogen content, good detonation properties, and improved impact and friction sensitivities which highlight their potential energetic applications.


Abstract The rainbow reflection effect describes the broadband spatial separation of wave spectral components caused by a spatially graded array of resonators. Although mainly studied in optics and acoustics, this phenomenon has recently been demonstrated both theoretically and experimentally for water waves travelling through an array of vertical cylinders. The scattering of two-dimensional linear water waves by an array of vertical, surface-piercing barriers is considered here, in which both the submergence and spacing between the barriers are spatially graded. The rainbow reflection effect arises naturally as wave energy temporarily becomes amplified at different locations depending on frequency. Band diagram calculations are used to demonstrate that this is a consequence of the wave gradually slowing down throughout the array. The wave/barriers scattering problem is then augmented by positioning heave-restricted, rectangular floating bodies equipped with a linear damping mechanism between each adjacent pair of barriers. A solution to the resulting boundary value problem is obtained using an integral equation/Galerkin method. Using constrained optimisation, passive rainbow absorbers are designed that achieve near-perfect absorption (i) over a discrete set of frequencies and (ii) over an octave. This suggests potential applications of rainbow absorbers in the design of smart coastal technologies.


Introduction Increasing evidence supports the viewpoint that alterations in the diversity and function of gastrointestinal bacteria contributes to IBS, and that increasing the mass of beneficial species, by consuming probiotics, may lower pathogenic bacteria numbers and help alleviate symptoms. Methods In this double-blind trial, a total of 360 adult patients with moderate-to-severe symptomatic diarrhoeapredominant IBS (IBS-D) were randomised to receive either treatment with the multi-strain probiotic Bio-Kult (14 different bacterial strains) or placebo for 16 weeks. The primary outcome measure was change in abdominal pain. The secondary outcomes included frequency of bowel motions, overall change in IBS-severity scoring system (IBS-SSS) and IBS specific quality of life (IBS-QoL). Results In comparison to placebo, treatment with probiotics significantly alleviated the severity of abdominal pain in patients with IBS-D: 69% reduction for probiotic versus 47% for placebo (p<0.001), equating to a 145 point reduction on the IBS-SSS. The level of patients rating their symptoms as moderate-to-severe was reduced from 100% at baseline to 14% in the multi-strain probiotic group by follow-up (month 5) versus 48% for placebo (p<0.001). In addition, the number of bowel motions per day from month 2 onwards was significantly reduced in the probiotic group compared with the placebo group (p<0.05). In addition to relieving symptoms, the probiotic markedly improved all dimensions of quality of life in the 34-item IBS-QoL questionnaire. No serious adverse events were reported. Conclusions The multi-strain probiotic was associated with significant improvement in symptoms in IBS-D patients, and was well-tolerated. These results indicate that probiotic supplementation confers benefit in IBS-D and deserves further investigation.Abstract OWE-032 Figure 1 Ibs-sss abdominal pain rating with probiotic (bio kult(X) or placebo(16 weeks treatment and1–month follow up The lower the score less the pain: *p≥0.002**p≤0.001:NS ≥Not significant


Objective: To investigate dental anomalies and the molecular etiology of a patient with Ellis–van Creveld syndrome and two patients with Bardet–Biedl syndrome, two examples of ciliopathies. Patients and Methods: Clinical examination, radiographic evaluation, whole exome sequencing, and Sanger direct sequencing were performed. Results: Patient 1 had Ellis–van Creveld syndrome with delayed dental development or tooth agenesis, and multiple frenula, the feature found only in patients with mutations in ciliary genes. A novel homozygous mutation in EVC2 (c.703G>C; p.Ala235Pro) was identified. Patient 2 had Bardet–Biedl syndrome with a homozygous frameshift mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7. Patient 3 had Bardet–Biedl syndrome and carried a heterozygous mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7 and a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa, obesity, pyometra with vaginal atresia, bilateral hydronephrosis with ureteropelvic junction obstruction, bilateral genu valgus, post-axial polydactyly feet, and small and thin fingernails and toenails, tooth agenesis, microdontia, taurodontism, and impaired dentin formation. Conclusions: EVC2, BBS2, and BBS7 mutations found in our patients were implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation.


Abstract Mixing processes associated with tropical marine boundary-layer cumuli are examined with a one-dimensional, steady-state model of the cloud and inversion layers which explicitly differentiates between cloud-scale and subcloud-scale motions. Physically, the clouds are modeled as an ensemble average of well-mixed turbulent bursts into an otherwise quiescent, subsiding environment. The cloud-base vertical velocity distribution is found from a new closure based on a simplified vertical momentum budget. The clouds are described by two free parameters, fractional area and a detrainment time scale. Faster detrainment rates are shown to be associated with undiluted clouds, in the sense that the cloud entrainment rate becomes zero. For this case, the cloud-scale fluxes dominate the boundary-layer mixing. Conversely, slower detrainment and large entrainment imply a diluted cloud, with the boundary-layer mixing dominated by the subcloud-scale turbulence. Simple qualitative arguments show that the vertically...


Nursing by two mother-infant pairs in a caged colony of Macaca fascicularis was monitored at 1-min intervals for 8 h beginning 8:30 a.m. BST, once a week for 3 months in the summer of 1973. Nursing occupied about 210 min in 8 daylight hours for the infants at 10 weeks of age, and the time spent nursing decreased at the average rate of 9.4 min per week until the infants were about 6 months old. The time spent nursing by the infants studied here resembles closely the times spent nursing by some other macaques and by baboons. In the course of a day the amount of time spent nursing varies significantly with a diurnal peak. If nursing by one mother-infant pair is independent of nursing by the other pair, then the time the two pairs spend nursing together would be a function of the product of the frequencies of nursing by each pair. The expected times for the pairs nursing together based on the hypothesis of independent events were significantly less than the observed times the pairs nursed together. Nursing, therefore, involves a positive influence or imitation of one nursing pair by the other. Nursing sessions involving both mother-infant pairs were longer on the average than sessions involving only one pair.


Background: Factor VIII (FVIII) prophylaxis is the standard of care for patients with hemophilia A; however, conventional FVIII products usually require frequent intravenous infusions (3-4 times/week). The safety, efficacy, and prolonged half-life of recombinant FVIII Fc fusion protein (rFVIIIFc) in previously treated children with severe hemophilia A were demonstrated in the phase 3 Kids A-LONG study ([NCT01458106][1], completed) and ASPIRE extension study ([NCT01454739][2], ongoing). Here, we report cumulative long-term data on the safety and efficacy of rFVIIIFc in children <12 years of age in these studies as of the second interim data cut (8 Dec 2014).

Methods: Subjects who completed Kids A-LONG and met the enrollment criteria for ASPIRE could participate in the individualized prophylaxis (IP; 25-80 IU/kg every 2-5 days, or 20-65 IU/kg on Day 1 and 40-65 IU/kg on Day 4 if twice weekly), or the modified prophylaxis (MP; for subjects in whom optimal dosing could not be achieved with IP) treatment groups. Subjects could switch treatment groups in ASPIRE once 12 years of age. For efficacy analyses, data were summarized according to the treatment group in which each subject participated, for the time period they were in that group; thus, subjects may be included in the analysis of more than one treatment group. Outcomes included: incidence of inhibitors (neutralizing antibody value ≥0.6 BU/mL identified and confirmed on 2 separate samples drawn approximately 2 to 4 weeks apart and performed at the central laboratory as measured by the Nijmegen-modified Bethesda assay), adverse events (AEs), annualized bleeding rate (ABR), treatment of acute bleeds, and changes to prophylactic consumption and dosing interval. Outcomes were analyzed over the cumulative duration of Kids A-LONG through the second ASPIRE interim data cut (8 Dec 2014).

Results: 61/67 subjects who completed Kids A-LONG enrolled in ASPIRE (<6 y, n = 30; 6 to <12 y, n = 31). As of the second interim data cut, 47 subjects were ongoing in ASPIRE; no subjects changed treatment groups during ASPIRE. Median (IQR) cumulative rFVIIIFc exposure days (EDs) for all subjects who received ≥1 intravenous injection (N = 69) were 190.0 (153.0-208.0) days; the median (interquartile range [IQR]) duration of rFVIIIFc treatment was 1.7 (1.5-2.0) years. No inhibitors were reported. The estimated inhibitor incidence rate (95% confidence interval) was 0.0% (0.0, 5.2) overall and 0.0% (0.0, 6.1) in subjects with ≥100 rFVIIIFc EDs (n = 59). The type and incidence of AEs observed were consistent with those expected for a pediatric hemophilia population . 95.7% of subjects reported ≥1 AE on-study; 36/448 were serious and 2/448 were assessed as related to rFVIIIFc treatment by Investigators. 30.4% of subjects experienced ≥1 serious AE; none were assessed by Investigators as related to rFVIIIFc. There were no reports of anaphylaxis or serious hypersensitivity events, and no serious vascular thrombotic events. Median ABRs for subjects on IP (n = 57) were generally lower with rFVIIIFc compared with prestudy FVIII (Figure).In the IP group, the ASPIRE Year 1 and Year 2 median (IQR) spontaneous ABRs were 1.0 (0.0-1.0) and 0.0 (0.0-2.3), respectively, for the <6 y cohort (n = 27), and 0.0 (0.0-1.0) and 0.0 (0.0-0.0), respectively for the 6 to <12 y cohort (n = 30).Overall, 79.8% and 95.8% of bleeding episodes were controlled with 1 or ≤2 intravenous injections, respectively . Among subjects treated with FVIII prophylaxis pre-Kids A-LONG who remained on a prophylaxis regimen (n = 54), the median (IQR) dosing interval was lengthened (prestudy FVIII: 2.3 [2.0, 2.3] days; on-study rFVIIIFc: 3.5 [3.5, 3.5] days) and the median (IQR) total weekly prophylactic consumption was similar (prestudy FVIII: 100.0 [78.0, 120.0] IU/kg; on-study rFVIIIFc: 95.0 [75.0, 113.0] IU/kg).

Conclusions: Longitudinal data from previously treated children with severe hemophilia A treated with rFVIIIFc in Kids A-LONG/ASPIRE confirm long-term safety, with no inhibitors observed in any subjects, and maintained efficacy in the prevention and treatment of bleeding. Low median ABRs were maintained with extended prophylactic dosing intervals, without increased factor consumption.

This research was funded by Biogen and Sobi. Biogen and Sobi reviewed and provided feedback on the abstract. The authors had full editorial control of the abstract and provided their final approval of all content.

![Figure][3]

Disclosures Young: Biogen: Consultancy, Speakers Bureau; Kedrion: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Baxter: Consultancy. Liesner: Pfizer: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Speakers Bureau; Octapharma: Consultancy, Honoraria, Research Funding, Speakers Bureau; SOBI: Consultancy, Honoraria, Research Funding, Speakers Bureau; BPL: Consultancy, Honoraria, Research Funding; Baxalta Innovations GmbH, now a part of Shire: Consultancy, Honoraria, Research Funding; Cangene: Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Biogen: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria. Pasi: Biogen: Consultancy, Honoraria; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Consultancy, Honoraria; Octapharma: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria. Nolan: Sobi: Research Funding; Biogen: Research Funding. Lethagen: Sobi: Employment. Cristiano: Biogen: Employment, Equity Ownership. Tsao: Biogen: Employment, Equity Ownership. Winding: Sobi: Employment. Mahlangu: Bayer: Research Funding, Speakers Bureau; Biogen: Consultancy, Research Funding, Speakers Bureau; CSL: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding; Amgen: Speakers Bureau; Biotest: Speakers Bureau; Baxalta: Consultancy.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01458106&atom=%2Fbloodjournal%2F128%2F22%2F1414.atom
 [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01454739&atom=%2Fbloodjournal%2F128%2F22%2F1414.atom
 [3]: pending:yes


OBJECTIVE
To investigate the expression of Bax and PHF20 in laryngeal squamous cell carcinoma (LSCC)and to discuss their relevance and the roles in carcinogenesis and development in LSCC.

METHOD
The expressions of Bax and PHF20 in the LSCC tissues and normal mucosa tissues adjacent to carcinoma were detected by SP immunohistochemistry assay. The relationship between the expressions of Bax and PHF20 and the clinicopathological characteristics including clinical stage, pathological type, histological grade and lymph node metastasis in LSCC were analyzed according to the clinical data.

RESULT
(1) The expressions of Bax and PHF20 were both significantly lower in the LSCC tissue than that in the normal laryngeal tissue (P < 0.01). (2) In clinical stage grouping, there were no statistical differences of the quantity and positive rate of Bax and PHF20 expressions among supraglottic, glottic and subglottic LSCC (P > 0.05). In histological differentiation grouping, the quantity and positive rate of Bax and PHF20 expressions decreased significantly in poorly differentiated LSCC compared with the well and moderately differentiated LSCCs (P < 0.01, P < 0.05, respectively). In T stage grouping, the quantity and positive rate of Bax and PHF20 expressions were both significantly higher in T1 + T2 compared with T3 +T4 (both P < 0.01). In addition, the quantity and positive rate of Bax and PHF20 expressions were both significantly higher in LSCC with lymph node metastasis compared to that without lymph node metastasis (both P < 0.01).

CONCLUSION
The lack of Bax and PHF20 might contribute to the carcinogenesis and development in LSCC. The positive expression of Bax and PHF20 maybe relative to T term degree, differentiation degree and lymphamatic metastasis of LSCC.


BACKGROUND
School-based body mass index (BMI) measurement has attracted much attention across the nation from researchers, school officials, legislators, and the media as a potential approach to address obesity among youth.

METHODS
An expert panel, convened by the Centers for Disease Control and Prevention (CDC) in 2005, reviewed and provided expertise on an earlier version of this article. The panel comprised experts in public health, education, school counseling, school medical care, and a parent organization. This article describes the purposes of BMI measurement programs, examines current practices, reviews existing research, summarizes the recommendations of experts, identifies concerns, and provides guidance including a list of safeguards and ideas for future research.

RESULTS
The implementation of school-based BMI measurement for surveillance purposes, that is, to identify the percentage of students in a population who are at risk for weight-related problems, is widely accepted; however, considerable controversy exists over BMI measurement for screening purposes, that is, to assess the weight status of individual students and provide this information to parents with guidance for action. Although some promising results have been reported, more evaluation is needed to determine whether BMI screening programs are a promising practice for addressing obesity.

CONCLUSIONS
Based on the available information, BMI screening meets some but not all of the criteria established by the American Academy of Pediatrics for determining whether screening for specific health conditions should be implemented in schools. Schools that initiate BMI measurement programs should evaluate the effects of the program on BMI results and on weight-related knowledge, attitudes, and behaviors of youth and their families; they also should adhere to safeguards to reduce the risk of harming students, have in place a safe and supportive environment for students of all body sizes, and implement science-based strategies to promote physical activity and healthy eating.


Television viewing distances, visual angles, and viewing angles were calculated for 217 children and 149 adults from 78 families. The data were obtained from time-lapse videotapes automatically recorded in the families' homes over 10-day periods. Viewing distance increases with age, and visual angle decreases with age. Viewers aged 17 years and younger viewed at an average distance of 225.3 em, at an average visual angle of 12.3 deg, and at an average viewing angle of 23.7 deg. Adult viewers watched TV at an average distance of 336.8 cm, an average visual angle of 6.6 deg, and at an average viewing angle of 23.3 deg. The best predictors of viewing location were (1) percentage of time the viewer watched TV from furniture, (2) room area, and (3) screen width.


The purpose of the study was to find out the effects of Aerobic exercise on selected physiological parameters among inactive young women. To achieve the purpose of the study thirty inactive young women were selected randomly as subjects fromWomen's Christian College, Nagercoil, Kanyakumari District, Tamilnadu, India and their age were ranged from 18 to 25 years. The subjects divided into two groups in equal numbers (N=20). Group I underwent Aerobic exercise group and group II acted as control group who did not attended any special training other than their daily college schedule curriculum. The duration of the training period was restricted into six weeks for three alternative days per week. The pre and post tests data were collected before and after the training period. The dependent variables pulse rate, and VO2 Max were tested by standardized test items respectively. The collected data from the two groups prior to and after the experimental treatments on selected variables pulse rate, and VO2 Max were statistically analyzed by using the statistical technique of dependent't' test and analysis of covariance (ANCOVA). In all the cases the level of confidence was fixed at 0.05 significant. The result of the study indicated that the experimental group had shown significantly improved in pulse rate, and VO2 Max variables among inactive young women due to the effects of aerobic exercise. However the control group did not shown any significant improvement on selected variables such as pulse rate, and VO2 Max.


This study aimed at understanding the processes of partnership between schools and universities in Physical Education's supervised curricular practicum. The approach was qualitative research and case study, using narrative interview with seven subjects as well as content analysis. The results showed contradictions in the process, since the institutions are distant in the model of practicum adopted. The challenge lies in abandoning a model that sees the university as the center of the process and move towards a model that includes schools and universities as educational places.


Rates of turnover for the posttranslational acetylation of core histones were measured in logarithmically growing yeast cells by radioactive acetate labeling to near steady-state conditions. On average, acetylation half-lives were approximately 15 min for histone H4, 10 min for histone H3, 4 min for histone H2B, and 5 min for histone H2A. These rates were much faster than the several hours that have previously been reported for the rate of general histone acetylation and deacetylation in yeast. The current estimates are in line with changes in histone acetylation detected directly at specific chromatin locations and the speed of changes in gene expression that can be observed. These results emphasize that histone acetylation within chromatin is subject to constant flux. Detailed analysis revealed that the turnover rates for acetylation of histone H3 are the same from mono- through penta-acetylated forms. A large fraction of acetylated histone H3, including possibly all tetra- and penta-acetylated forms, appears subject to acetylation turnover. In contrast, the rate of acetylation turnover for mono- and di-acetylated forms of histones H4 and H2B, and the fraction subject to acetylation turnover, was lower than for multi-acetylated forms of these histones. This difference may reflect the difference in location of these histones within the nucleosome, a difference in the spectrum of histone-specific acetylating and deacetylating enzymes, and a difference in the role of acetylation in different histones.


Abstract Aim: To examine the gestational age-specific distribution of twin birth weight discordance. Methods: We analyzed all liveborn twin sets between 28 and 40 weeks' gestation from the United States 1995–1998 Multiple Matched Birth Data Set compiled by the National Center for Health Statistics. We calculated the 50th and 95th percentiles of birth weight discordance at each gestational age. Neonatal mortality rates were calculated for discordant twins at the 95th percentile of birth weight discordance for each gestational age. Results: At older gestational ages, the 95th percentile of birth weight discordance resulted in an inter-twin birth weight difference of approximately 25%, a value often used to define twins as birth weight discordant. However, at earlier gestational ages, the 95th percentile of birth weight discordance was greater, reaching nearly 50% at 28 weeks. Conclusions: The inter-twin birth weight difference at the 95th percentile is greater at lower gestational ages, possibly illustrating the different nature or severity of twin birth weight discordance at an earlier gestational age.


This paper presents batch-fabrication lamination approaches for the realization of large arrays of high-power, short-duration gas generator actuators (GGAs), and system implementation approaches for integration of these GGAs into a spinning, axisymmetric bluff body for the purpose of generating steering forces on the body. The GGAs are tested to determine the impulse delivered per GGA and the time required delivering the impulse. The arrays of GGAs are connected with control electronics and integrated into a test platform. The final result is a force generation system for the time-controlled delivery of forces to a spinning body; fabrication and characterization of the GGA component of this system will be presented here.


Summary To investigate the mechanisms by which the isopod Limnoria tolerates copper, chromium and arsenic when tunnelling CCA-treated wood in the marine environment, digestive caecae of specimens of L. quadripunctata from CCA-treated and untreated Pinus sylvestris sapwood were examined using transmission electron microscopy (TEM) and energy dispersive X-ray detection (EDX). Copper-containing granules were found to be present in the small cells of the digestive caecae (midgut) of Limnoria from both treated and untreated wood. However, individuals tunnelling treated timber contained a greater number of granules, with six types of morphology being distinguished of which only two were present in Limnoria from untreated wood. The presence of copper-containing granules in Limnoria from untreated timber may be explained by the ability of this isopod to acquire and store copper from seawater for use in enzymes and blood pigments. The increased number of copper granules in individuals tunnelling treated wood was believed to result from elevated levels of this element in the food substrate. This ability to store copper allows these organisms to tolerate this metal in the wood substrate and may explain how this organism is able to attack CCA-treated wood in service. No chromium, or arsenic, was detected in the digestive caecal cells.


We study the efficiency of the approximate solution of ill-posed problems, based on discretized noisy observations, which we assume to be given beforehand. A basic purpose of the paper is the consideration of stochastic noise, but deterministic noise is also briefly discussed. We restrict ourselves to problems which can be formulated in Hilbert scales. Within this framework we shall quantify the degree of ill-posedness, provide general conditions on projection schemes to achieve the best possible order of accuracy. We pay particular attention on the problem of self-regularization vs. Tikhonov regularization. Moreover, we study the information complexity. Asymptotically, any method which achieves the best possible order of accuracy must use at least such amount of noisy observations.


Abstract Objectives: The advantages of intrauterine contraception (IUC) are well established (highly effective, low discontinuation rate, easy to use, low cost, and suitable for immediate postpartum use), but low levels of use in many countries and declining use in others are causes for concern. Due to the ongoing Zika virus outbreak, public health officials are calling for the continued practice of safe sex and the delay of pregnancy. Our study was conducted to assess the current situation of IUC availability and provision in Latin America and to determine the role of national policies in meeting the contraceptive needs of the populations in these countries. Methods: A survey was conducted in Latin America and the Caribbean between December 2015 and January 2016 to assess national policies with regard to IUC provision, availability and accessibility. 18 countries participated. Results: All responding countries had national policies on IUC. Many in the public sector provided the intrauterine device (IUD) free of charge, but the levonorgestrel-releasing intrauterine system (LNG-IUS) was generally available in the private sector. Some countries had very restrictive policies on who was permitted to carry out IUC insertions, but most permitted a range of health professionals to do so. Immediate postpartum IUC insertion was uncommon. Some countries placed restrictions on IUC use in women who were nulliparous, young, at high risk of catching a sexually transmitted infection or who had multiple sexual partners. Conclusions: IUC is underused in Latin America. The study reveals policy level barriers that may impede access to IUC, one of the most effective, long-acting, non-hormonal, reversible contraceptive methods. Governments should consider reviewing and rethinking their policies on contraception to ensure IUC service provision among populations at high risk of unplanned pregnancy, especially those vulnerable to Zika virus.


Uranium a radioactive element and a source of radioactive pollution directly influence the humans those are exposed to it. Sometimes high uranium content is present in phosphate rock used for the manufacturing of fertilizer. Besides being heaviest naturally occurring metal, uranium is one of the primeval radionuclides that can be found in low levels within all rocks, soil and water. In the record of history never has a scientific discovery so profoundly affected the course of human fate as the discovery of atomic energy. Therefore, its potential for destruction is massive and its use for economic purpose is limitless. In present era, rightly known as the atomic age, the emission of radiation in the form of rays or particles called radioactivity. There are many deposits of uranium in Pakistan and their uses cause much positive as well as negative impact on humans and environment. Uranium having a potential to cause a spectrum of adverse health effects ranging from renal failure and diminished bone growth to damage to DNA, because uranium possesses both chemical toxicity as well as radioactivity, assessing the relative contributions of each to its toxic profile is difficult. By knowing these risk factors, there is a need of hour that we should work on the impacts of uranium in environment and humans to devise new techniques and measurements for the reduction of uranium pollution and this will be helpful for others to devise more acceptable and facile methods in future. In this article, aimed to discuss toxicology of uranium, sources of emission as well as their impact on human health and environment.


Recent research has aimed to identify specific phytochemicals in Brassica vegetables, such as sulforaphane in broccoli, that may confer protection against cancer. Clinical, dietary, and policy implications are discussed.


Recently the HSRC released its report on the results of its third and most recent household prevalence survey. The main conclusion of their analysis is that "some solid progress has been made in the fight against the disease in the past few years, especially among teenagers and children". In particular the authors conclude:
• that HIV prevalence at national level has decreased amongst children aged 2-14, from 5.6% in 2002 to 2.5% in 2008
• that there was a substantial decrease in incidence in 2008 in comparison to 2002 and 2005, especially for the single age groups 15, 16, 17, 18, and 19
• that HIV prevalence has decreased amongst youth aged 15-24 from 10.3% in 2005 to 8.6% in 2008, and
• that HIV prevalence among adults aged 15-49 has declined between 2002 and 2008 in the Western Cape, Gauteng, Northern Cape and the Free State, "with the largest decline of 7.9 (sic) percentage points in the Western Cape" .

How reliable are the results from the survey and how reasonable are these conclusions?


Abstract Background Growing up on a cattle farm and consuming raw cow's milk protects against asthma and allergies. We expect a cattle‐specific protein as active component in this farm effect. Methods Dust was collected from cattle and poultry stables and from mattresses of households. Urine was obtained from cattle, and ambient aerosols were sampled. Samples were analysed for BLG by SDS PAGE/immunoblot and mass spectrometry, and for association with metals by SEC‐ICP‐MS. PBMC of healthy donors were incubated with BLG +/− zinc, and proliferation and cytokines determined. BALB/c mice were pre‐treated intranasally with stable dust extract containing BLG or depleted of BLG, and subsequent allergy response after sensitization was evaluated on antibody and symptom level. Results A major protein in dust from cattle farms and ambient air was identified as BLG. Urine from female and male cattle is a major source of BLG. In dust samples, BLG was associated with zinc. In vitro, zinc‐BLG provoked significantly lower proliferation of CD4+ and CD8+ cells while inducing significantly higher levels of IFN‐γ and IL‐6 than the apo‐BLG devoid of zinc. In vivo, pre‐treatment of mice with dust extract containing BLG resulted in lower allergy symptom scores to BLG and unrelated Bet v 1 than pre‐treatment with extract depleted of BLG. These in vitro and in vivo effects were independent of endotoxin. Conclusion The lipocalin BLG is found in large amounts in cattle urine, accumulates in bovine dust samples and is aerosolized around farms. Its association with zinc favorably shapes the human cellular immune response towards Th1‐cytokines in vitro. BLG together with zinc in stable dust protects mice from allergic sensitization. BLG with its associated ligands may in an innate manner contribute to the allergy‐protective farm effect.


In this thesis, we focus on the identification of mental states described according to the definition of awareness and wakefulness. Using algorithmic methods, we show that it is possible to differentiate between two brain states based on the brain electrical activity collected by EEG. We begin by explaining the overall theoretical framework which enabled us to develop the detection of brain states. It starts with data acquisition. Following that, we analyse the pre-processing of the data before the extraction of features. Finally, we go on to statistically evaluate the results. In order to achieve this task, we propose four experiments. We will first focus on exploring different brain states for patients in Intensive Care Unit (ICU) such as coma and quasi-brain-death states. To distinguish these states, we use a signal processing method based on the EEG signal phase. A phase synchrony index based on Shannon entropy was used to separate the two states. Statistical validation revealed a significant difference between the two via delta-alpha and theta-alpha frequency couplings. Next, we studied the neuronal mechanisms which is used to understand consciousness. We did that by using dipole modelling. This method was applied to local-global experiment and the paradigm of auditory deviance with two hierarchical levels. A modulation of this experiment is generated by a sedative Propofol to study the effect on conscious states. This experiment was analysed in greater detail using the Imaging Method to do the source localisation. We analysed three different time-windows. The first window corresponds to the local effect during the initial response of the brain. We assume that this input is related to auditory
areas and activates the temporal lobe. The second window is at the interface between the local effect and the global effect. In here we are especially interested in the interaction between these two effects during the second window. Finally, the third window will enable us to study the overall effect. We hypothesize a global activation of neural networks corresponding to consciousness as described by the global workspace theory. The third experiment focused on brain states high-level athletes experience during a cognitive task. Two different groups of cyclists, endurances and sprinters,
were asked to do a Stroop task for 30 minutes. We studied the influence of the task and the potential differences in brain activity between the two groups. We found through the frequency analysis that the brain activity between the two groups can be distinguished, but was not modified by the cognitive task.
Finally, we studied the influence of the sensorimotor loop on the brain. A physical task was applied, consisting in lifting a weight with two measurements, where the lifting arm can also be in fatigued state. Using sources reconstruction from EEG, we studied the impact of weight-lifting and the physical fatigue upon neuronal activities and the neuronal origins of these effects. We found that only
weight has an effect, whereas fatigue effect is not significant. We conclude with a discussion of the mechanisms of consciousness analysed via algorithmic methods and some future work for the possibility to distinguish better between different cognitive states.


This article presents a brief overview of the ENIAC and its place in history. In order to indicate where a program was or whether a valve was malfunctioning, the ENIAC engineers attached small bulbs throughout the machine, which could convey this information to the programmers. For the purposes of the public demonstration in 1946, these tiny bulbs were made more prominent by the addition of translucent hemispheres that were actually halved ping-pong balls. Long after miniaturization made this feature redundant, sci-fi movies persist in presenting it as an essential element of the all-powerful computers whose control panels flash malevolently as they emit their sinister messages. A more substantial effect of development of the birth of the ENIAC in Philadelphia is that the city acquired a site important for being the place where ideas started a revolution. As the place where the first operating computer of its sort was constructed, the Moore School is one to which historians will continue to look as current events turn into history.


The importance of appropriate growth media for propagation of Annona muricata seedlings cannot be over emphasized. An experiment was conducted to investigate the effects of biochar and organic soil amendments on seedling development of Annona muricata using different potting media. The treatments were Control; Topsoil only (T0), Mineralized goat dung (T1), Mineralized saw dust (T2), Mineralized poultry dropping (T3) and Mineralized biochar (T4). The experiment was laid out in Completely Randomized Design (CRD). Parameters accessed include seedling height (cm), collar diameter (cm) and number of leaves.  The data collected were subjected to analysis of variance and significant means were separated using Duncan multiple range test at 0.05 significant level. Result shows that Mineralized biochar had the best performance in seedling height, collar diameter and number of leaves with mean values of 26.703±1.5488, 4867±0.22904 and 4.4451±1.55031 respectively. While the least performance in seedling height, collar diameter and number of leaves was recorded in the control with mean values of 19.986±1.1265, 0.3230±0.17363 and 3.6765±1.14724 respectively. However, there were significant differences in seedling heights and collar diameter among the treatment types at 5% level of probability, but the number of leaves was not significant. Annona muricata seedlings thrives excellently in biochar potting media. Hence, the use of biochar potting media should be adopted as the best growth media for early growth and development of Annona muricata seedlings.


Th17 cells have been linked to the emergence of many autoimmune inflammatory conditions as well as defense against fungal pathogens. Early differentiation and expansion of Th17 cells relies on key cytokines that signal through STAT3, including IL-6 and IL-21. Later STAT3-dependent signals from IL-23 are critical for gain of inflammatory function by effector Th17 cells. Thus, development of drugs that target STAT3 or its upstream receptors are a major research focus to alleviate disease. However, the requirements for STAT3 signaling in effector Th17 cells remain elusive. Here, we developed a model to study the effect of STAT3 deficiency specifically in effector Th17 cells in EAE, an animal model of multiple sclerosis. Our data show that mice lacking STAT3 in effector Th17 cells are resistant to EAE development. Unexpectedly, we demonstrate that in Th17 cells, STAT3 is not required for maintenance of Th17 lineage commitment or Th17 cytokine production in vivo. To determine mechanisms by which STAT3 regulates Th17 effector cells to promote development of autoimmune inflammation, we performed bioinformatics analysis of the transcriptome of effector Th17 cells isolated from lymph nodes (LN) at day 10 (onset) of EAE. This revealed that STAT3 regulates expression of genes associated with particular cell-death pathways, and pathways associated with proliferation and T cell mediated tissue damage. Corresponding to these changes in gene expression, we found that STAT3 deficient effector Th17 cells were reduced in numbers in LN and target tissue during EAE. Our data reveal a hitherto unappreciated mechanism for STAT3 in regulating effector Th17 cells, which have major implications for use of STAT3-targeted therapies.


Abstract The approach to the issue of shrinking cities is undergoing constant changes. Originally, this process was referred primarily to the progressing depopulation connected with a deteriorating economic situation. Presently, works on shrinking cities mainly focus on the challenges posed by the problem rather than the delimitation questions. Do the shrinking also apply to the situation of small towns, and if so, to what extent may small towns shrink? Being conscious of the multidimensional nature of the topic discussed, the authors took measures aimed at singling out a group of shrinking towns from the whole set of small towns in Poland. The identification of depopulating centres consisted in pointing to those shrinking both in terms of their demography and economy. This type of research gives rise to all types of methodological problems such as which tools should be used to measure town shrinking or which data should be selected for the research, an issue particularly important for small towns where the range of indicators available is rather limited. What conclusions may be drawn from the conducted analysis? Do small towns in Poland shrink? On the basis of the conducted research the answer is no. With regard to demography, the process of shrinking concerns only 30 towns (4.5%). And this group includes only four which additionally shrink in economic terms.


Quantitative time-lapse studies require precise knowledge of the pressure response of rocks sampled by a seismic wave. Usually this knowledge is obtained from measurements of ultrasonic velocities as a function of pressure. These measurements are typically made on reservoir sandstone samples. However, if the reservoir is composed of sand and shale layers, the response of shales as well as sands has to be taken into account. The pressure response of shales is quite different from that in sand: since shales have very low permeability, an increase of pore pressure in the sand will cause an increase of confining pressure in the intra-reservoir shale. To estimate the effect of intra-reservoir shale on the time-lapse response to depletion or injection, we compute the combined seismic response as a function of net to gross (NTG – sand-shale proportion). This is done by applying Backus average using typical shale and sandstone stress sensitivity for an oil field located in Campos Basin, Brazil. For a typical NTG of 0.6, there is an error of approximately 35% in reflection coefficient estimation if these shales are neglected. Consequently, not considering the small shales intra-reservoir may mislead quantitative 4D studies. We suggest expanding this approach to 3D models in order to incorporate other geomechanical effects.


Purpose
This paper aims to provide new empirical evidence on the non-performing loan (NPL) determinants of the EU conventional banks, in the context of macroeconomic factors, dimensions of country governance and bank-specific characteristics.

Design/methodology/approach
The panel data sets of 1,053 conventional banks were obtained over the period of 2007-2016. The Hodrick–Prescott filter was adopted to extract business cycle and credit cycle from real gross domestic product and credit to the private non-financial sector, correspondingly. System-generalised methods of moment was then used to identify the significant determinants of NPL.

Findings
The empirical results reveal that NPL is primarily driven positively by lagged-one NPL and risk profile. In consonance with the skimping hypothesis, NPL has a significant positive relationship with the cost efficiency. The empirical finding of the business cycle coincides with the Austrian business cycle theory. Particularly, NPL is relatively low during rapid economic growth of credit-sourced business boom. Whereas, business bust happens when credit creation runs its course and is associated with high NPL. This paper encapsulates that NPL is driven by not only macroeconomic factors and bank-specific characteristics but also the dimensions of country governance.

Practical implications
Policymakers should introduce policies that are geared towards proper dimensions of country governance.

Originality/value
The novelty of this research does not rely on the multidimensions of NPL determinants but on the disentanglement of the conventional banks with dual identity (i.e. Islamic banks, cooperative banks and ethical banks). It considers business cycle, credit cycle and previous NPL as the potential determinants.


AIDS stigma refers to prejudice and discrimination directed at people or groups perceived to have HIV/AIDS (Herek, 1999). Although AIDS stigma has been found in adolescent and adult populations, few researchers have explored it among children. Misconceptions about people with AIDS (PWA) might lead to negative attitudes toward PWA and obstruct HIV prevention efforts. The authors assessed 110 Puerto Rican children's attitudes toward PWA using drawings (n = 65) and stories (n = 45). Although participants held stigmatizing attitudes toward PWA across both methods, the approaches captured different beliefs and attitudes. Drawings depicted PWA as physically deteriorated and performing socially condemned behaviors, whereas stories describing PWA highlighted children's fear of contagion and death. Stigma toward PWA was more pronounced than toward other illnesses (e.g., cancer). The study highlights the importance of assessing children's attitudes through creative data collection procedures.


A 7-year-old male with a history of blunt trauma to the abdomen and diagnosis of perinephric hematoma in contrast-enhanced computed tomography (CT) presented with increasing peri-nephric collection (after ~1.5 months) in the serial ultrasound examinations. The patient was referred to the department of nuclear medicine for the assessment of this collection as well as renal function. In 99mTc-diethylenetriamine pentaacetate renal scintigraphy, progressively increasing radiotracer activity was noted inferolaterally to the left kidney, separated from the same by a photopenic area. Single-photon emission computed tomography/CT revealed a peri-nephric urinoma in relation to the previously diagnosed hematoma at the lower pole; which was communicating with the pelvi-calyceal system (PCS). Not only did the renal scintigraphy aid in the diagnosis of urinoma but it was also able to show that it was communicating freely with the PCS and that the rest of the renal parenchyma was functioning adequately. This multi-faceted assessment in a single investigation allowed clinicians to opt for the conservative management despite the increasing size of urinoma in the early follow-up.


Morphological data generated from light and electron microscopy form the basis of our understanding of avian morphogenesis. Because chicken embryos are readily and cheaply obtained and are easily accessible for experimental manipulation, morphogenetic processes have been studied extensively in this species. Such studies have allowed us to identify the cells involved during morphogenesis, observe the shape changes or cellular translocations that accompany a morphogenetic process, and determine the timing of these events. Elucidation of the molecular basis of morphogenesis has awaited the integration of several additional approaches. Among these are experimental embryology, which has allowed us to understand cellular behavior associated with morphogenesis; immunocytochemistry, which has identified the macromolecular cues that regulate cell movements and the environmental factors that control them; and molecular techniques, which will permit us eventually to clarify the genetic regulation of morphogenesis. Although current research in development is heavily biased towards molecular biology, morphological studies continue to frame the questions that are now being addressed using molecular techniques.


We examine the effects of multiphoton absorption, free carriers, and disorder-induced linear scattering in slow-light photonic crystal waveguides. We derive an analytic formulation for self-phase modulation including the group velocity scaling of the nonlinear phase shift in materials limited by three-photon absorption as a representative nonlinear process. We investigate the role of free carriers and derive an approximate critical intensity at which these effects begin to strongly modify the optical field. This critical intensity is employed to determine an optimal group index for the self-phase modulation in the slow-light devices. These observations are confirmed with numerical modeling.


Importance Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes. Objective To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. Design, Settings, and Participants The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. Interventions Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations. Main Outcomes and Measures The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval. Results Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, −∞ to 10.5%; P=.19). Conclusion and Relevance This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment. Trial Registration clinicaltrials.gov Identifier: NCT01731431


The purpose of this study is to analyze the relationships between the quality of leadership, achievement recognition, and teamwork with the organizational climate and quality of life at work. A questionnaire was prepared that included all items of the variables in this study of the scales ECO IV and ISTAS21. The sample selected was composed by 1179 workers of a multinational company; mediation and moderation analysis was applied with Process v3.4. The results of this study suggest that teamwork exerts significantly the expected mediating effect in the relationship between the quality of leadership and the organizational climate. However, recognition of achievement does not produce moderation in the relationship between leadership quality with the organizational climate. To sum up, leadership quality, teamwork, and recognition of achievements improve the perception of the organizational climate and quality of life at work. Therefore, the organization must establish its own leadership style that allows it to achieve its objectives and improve the quality of life of workers.


Abstract. Developments of LiDAR technology are decreasing the unit cost per single point (e.g. single-photo counting). This brings to the possibility of future LiDAR datasets having very dense point clouds. In this work, we process a very dense point cloud (~200 points per square meter), using three different methods for segmenting single trees and extracting tree positions and other metrics of interest in forestry, such as tree height distribution and canopy area distribution. The three algorithms are tested at decreasing densities, up to a lowest density of ~5 point per square meter. Accuracy assessment is done using Kappa, recall, precision and F-Score metrics comparing results with tree positions from groundtruth measurements in six ground plots where tree positions and heights were surveyed manually. Results show that one method provides better Kappa and recall accuracy results for all cases, and that different point densities, in the range used in this study, do not affect accuracy significantly. Processing time is also considered; the method with better accuracy is several times slower than the other two methods and increases exponentially with point density. Best performer gave Kappa = 0.7. The implications of metrics for determining the accuracy of results of point positions' detection is reported. Motives for the different performances of the three methods is discussed and further research direction is proposed.


Background

Early developmental impairment (EDI) is common and has many aetiologies and, therefore, potential investigations. There are several published guidelines recommending aetiological investigations, and paediatricians' views of them varies. Little is known on the thought processes underlying clinical decisions in investigating EDI. This study aimed to describe the thought processes affecting clinical decisions on the investigation of EDI within a nationalised health care system.
Methods

A qualitative descriptive study using semi-structured qualitative interviews performed in person or via video link with paediatricians who see children with EDI in England. As part of the interview, a case study of a fictional disease, Cavorite deficiency, modelled on biotinidase deficiency, was given to participants with the cost of testing, incidence and likelihood it would respond to treatment. This allowed exploration of cost without encumbrance from predisposing views and training on the condition. Thematic analysis was performed by iterative approach. Where participants stated they wanted to redirect money from investigations to treatment, were that even possible, we asked which services they would like to be better funded in their area.
Results

Interviews were conducted with 14 consultant paediatricians: 9 Community / Neurodisability, 2 General paediatricians, and 3 Paediatric Neurologists. Two themes were identified: the value of an aetiological diagnosis to families and managing risk and probability when investigating EDI. The latter contained 4 subthemes: 'circumspection' involved blanket investigations chosen irrespective of phenotype and high regard for guidelines; 'accepting appropriate risk' involved participants choosing investigations based on clinical phenotype, recognising some aetiologies would be missed; consultants found they 'transitioned between practices' during their career; and 'improved practice' was thought possible with better evidence on how to stratify investigations based on phenotype. Services that were most frequently reported to need additional funding were therapy services, early community developmental services, management of behaviour, sleep and mental health, and educational support.
Conclusions

There are many factors that influence paediatricians' choice of aetiological investigation in EDI, but clinical factors are the most important. Paediatricians want better evidence to allow them to select the right investigations for each child without a significant risk of missing an important diagnosis.


SUMMARY To gain protection under the International Convention for the Protection of New Varieties of Plant, new plant varieties must be distinguishable from existing varieties in at least one important characteristic. Assessment of quantitative characteristics often uses a procedure based on analysis of variance of variety-by-year means for 2 years of trials. In the current paper, a new method is described that can identify those reference varieties that are so different from a candidate that there would be no reason to compare them in the subsequent year, resulting in potential cost savings. It is more objective and transparent than existing practice for quantitative characteristics based on expert opinion. The method calculates thresholds for quantitative characteristics. The thresholds are defined so that if in the first year the difference between two varieties in a characteristic is larger than the characteristic's threshold then it is highly likely that the varieties would be distinct after 2 years. Thresholds were derived based on statistical predictions of the full decision after 2 years using the first year results combined with historical data. It is shown that these thresholds are sensitive to yearly heterogeneity in the variety-by-year variation. The method accommodates this heterogeneity by modelling yearly residual variances with the inverse gamma distribution. This extension meant that exact analytical formulae were not available so an approximation was suggested. Using simulation it was found that the approximation was reasonable; for thresholds corresponding to a high probability of distinctness, the approximate thresholds were a little higher than required. The method was evaluated on a 19-year data set for field pea, comparing decisions based on first year thresholds with those based on the full 2 years. It was found that with the probability of distinctness set at 0·99, the calculated thresholds were generally lower than the existing expert-set thresholds but had acceptable levels of false positives and false negatives.


Background Hypersecretion of mucin 5AC (MUC5AC) is a prominent feature of chronic rhinosinusitis with nasal polyps (CRSwNP) and autophagy plays a pivotal role in this process. TNF receptor-associated factor 6 (TRAF6) functions as a signal transducer in many inflammation diseases, whereas the correlation between TRAF6 and autophagy in CRSwNP remains unclear. Objective To investigate the role of TRAF6 in the human neutrophil elastase (HNE)-induced autophagy and mucin MUC5AC over-expression in CRSwNP. Methods Tissue specimens were obtained from control subjects and patients with CRSwNP. The relationships between HNE, TRAF6, autophagy, and MUC5AC were investigated. The effect of TRAF6 on HNE-mediated autophagy and hypersecretion of MUC5AC was assessed by in-vitro culture of HNECs treated with human recombinant HNE. Results Patients with CRSwNP had more protein expression of HNE, MUC5AC, TRAF6, and light chain (LC3B), and increased levels of Beclin-1(BECN1) and autophagy-related gene 5 (ATG5) in mRNA level. Treatment of nasal epithelial cells with recombinant HNE induced the upregulation of TRAF6, autophagy, and MUC5AC. Alternatively, si-TRAF6 or autophagy inhibitor treatment mitigates the hyperexpression of MUC5AC before incubating with recombinant HNE. Conclusion HNE promotes autophagy through TRAF6, resulting in hyperexpression of MUC5AC in CRSwNP.


Estrogen and progesterone receptor binding activity was measured in 22 intracranial meningioma surgical specimens. None of the tumors was estrogen receptor-positive, whereas 19 were progesterone receptor-positive. Of these 19 patients, all demonstrated significant computed tomographic (CT) evidence of peritumoral edema. None of the 3 patients who lacked progesterone receptor binding had CT evidence of peritumoral edema (P less than 0.005). Peritumoral edema associated with intracranial meningiomas seems to be related, at least in part, to progesterone binding activity. This implicates the potential use of progesterone antagonists for the treatment of incompletely resected or recurrent meningiomas.


The issue of mobile devices' security is now of great interest as they store and process data more valuable for users than the data stored and processed on personal computers. This paper deals with the development of models of a threat of unauthorized access to confidential information of subscribers to cellular networks, namely: mathematical model of the brute force attack, mathematical model of attacks using software exploits, mathematical model of an attack using additional equipment for its implementation, and mathematical model of attacks using instrument bugs and malicious logic. The article also discloses approaches to the protection of confidential information in cellular communication networks. The implementation of mathematical models discussed in the paper will significantly enhance the information security of mobile devices.


Thermokarst lake formation in ice-rich yedoma deposits in north Siberia has a major impact on regional landscape morphology, hydrology, and biogeochemistry. Detailed assessment of lake distribution characteristics is critical for understanding spatial and temporal lake dynamics and quantifying their impacts. The distribution of thermokarst ponds and lakes at three different sites with ice-rich permafrost (Bykovsky Peninsula, SW Lena Delta, and Cherskii) in northeast Siberia was analysed using high-resolution remote sensing and geographical information system (GIS) tools. Despite similarities in geocryological characteristics, the distribution of thermokarst lakes differs strongly among the study regions and is heavily influenced by the overall hydrological and geomorphologic situation as a result of past lake-landscape dynamics. By comparing our high-resolution water body dataset with existing lake inventories, we find major discrepancies in lake distribution and total coverage. The use of low-resolution lake inventories for upscaling of thermokarst lake-related environmental processes like methane emissions would result in a strong underestimation of the environmental impacts of thermokarst lakes and ponds in Arctic lowlands.


Global agreements in place to reduce methane emissions in livestock are a potential threat to food security. Successful but independent breeding strategies for improved production and lower methane are in place. The unanswered questions are whether these strategies can be combined and how they impact one another, physically and economically. The New Zealand economy is largely dependent on pastoral agriculture from grazing ruminants. The sheep industry produces ∼20 million lamb carcasses for export each year primarily from grass. Methane emitted from the fermentation of forage by grazing ruminants accounts for one-third of all New Zealand's greenhouse gas emissions. Here, we use sheep selection lines bred for divergent methane production and large numbers of their relatives to determine the genetic and phenotypic correlations between enteric methane emissions, carcass yield, and meat quality. The primary objectives were to determine whether previously shown physiological differences between methane selection lines (differing by ∼12% in methane) result in a negative impact on meat production and quality by measuring close relatives. The results show no negative effects of breeding for lowered methane on meat and carcass quality. Gross methane emissions were highly correlated with liveweight and measures of carcass weight and negatively correlated with dressing-out percentage and fat yield (GR). Trends were similar but not significant for methane yield (g CH4/kg DMI). Preliminary evidence, to date, shows that breeding for low methane may result in animals with higher lean yields that are economically favorable even before carbon costs and environmental benefits are taken into account. These benefits were seen in animals measured for methane on fixed intakes and require validation on intakes that are allowed to vary.


The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed to combat additional SARS-CoV-2 variants or novel CoVs. Here, we describe small molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation mediated innate immune responses. The compounds inhibiting Mac1 were discovered through high-throughput screening (HTS) using a protein FRET-based competition assay and the best hit compound had an IC50 of 14 µM. Three validated HTS hits have the same 2-amide-3-methylester thiophene scaffold and the scaffold was selected for structure-activity relationship (SAR) studies through commercial and synthesized analogs. We studied the compound binding mode in detail using X-ray crystallography and this allowed us to focus on specific features of the compound and design analogs. Compound 27 (MDOLL-0229) had an IC50 of 2.1 µM and was generally selective for CoV Mac1 proteins after profiling for activity against a panel of viral and human ADP-ribose binding proteins. The improved potency allowed testing of its effect on virus replication and indeed, 27 inhibited replication of a mouse hepatitis virus, a prototype CoV. Compound 27 is the first Mac1 targeted small molecule demonstrated to inhibit coronavirus replication in a cell model. This, together with its well-defined binding mode, makes 27 a good candidate for further hit/lead-optimization efforts.


ABSTRACT The 1970s is often characterised as the decade of Australia's "new nationalism", expressed most potently in a wave of cultural activity nurtured by government funding. The figure of the ocker was central to this new nationalism, particularly in film. The ocker, a contemporary masculine archetype devoted to beer, sex and swearing, was a star of Australian films such as The Adventures of Barry McKenzie, Alvin Purple, Petersen and Don's Party. Yet few scholars have considered the ocker in a gendered context, remarkable when we consider that while the ocker films were being produced, the women's liberation movement was mounting a radical challenge to Australian cultural, social and political norms. What new understandings of 1970s society and culture might result if we read the new nationalist ocker and women's liberation in the same frame? This article examines the relationship between ocker culture and women's liberation in the 1970s. It argues that we can read new nationalist popular culture as a site of gendered cultural contest, with a particular focus on feminist responses to ocker culture, including Alvin Purple, and a reading of the film Petersen.


In this study, stress-relaxation performance of HDPE-based injection-molded composites containing four types of natural fibers (i.e., wood flour, rice hulls, newsprint, and kenaf fiber) at 25 and 50 wt% contents, and the effect of prescribed strain levels were investigated. The results indicated that incorporating more filler causes lower relaxation values and rates, and stress retention and prescribed strain level were reversely correlated. Among the studied filler types, wood flour and kenaf fiber presented more similar behaviors, whereas newsprint resembled rice hulls performance. Strain—time superposition was applied to the experimental data. Due to complex rheological behavior of the studied composites, single horizontal shifting method, with respect to strain levels, was found to be inadequate to satisfactorily superpose data.


We present a system for X-ray tomography using a coded aperture. A fan beam illuminates a 2D cross-section of an object and our coded aperture system produces a tomographic image from each static snapshot; as such, we can reconstruct either a static object scanned in 3D or an x-ray video of a non-static object.


Although efforts to regulate securities at a supranational European level date back to the first company law directive in 1968, it is only since the promulgation of the 1999 Financial Services Action Plan that the playing field has shown any real leveling for market participants. Now, since the adoption in June 2001 of the European Securities Committee as a rule-making authority implementing financial services directives, European securities regulation has emerged as a new and discrete field of legal scholarship. This authoritative book, by a well-known scholar who has been following the European frontier of securities regulation for over a decade, is the first to systematically map this dramatically accelerating new discipline and open the field to research, development, and specialization. Approaching the subject along six major avenues--the value of substantive rules; regulatory harmonization; the underlying regulatory methodologies of enacted and proposed European directives; the common market prospectus for securities offerings; investment services; and insider trading--Professor Warren never loses sight of the historical context within which European securities regulation has developed, nor of the global economic environment in which it must meet exacting standards of efficiency and transparency. His analysis clearly explains the securities implications of the European laws already adopted as a result of the European Commission's implementation of the Financial Services Action Plan (including the European Company Statute), and also points out the areas that still demand legislative and regulatory attention (including the essential development of an efficient centralized orcross-linked clearance and settlement system).


ABSTRACT The susceptibilities to telithromycin of 203 Streptococcus pneumoniae isolates prospectively collected during 1999 and 2000 from 14 different geographical areas in Spain were tested and compared with those to erythromycin A, clindamycin, quinupristin-dalfopristin, penicillin G, cefotaxime, and levofloxacin. Telithromycin was active against 98.9% of isolates (MICs, ≤0.5 μg/ml), with MICs at which 90% of isolates are inhibited being 0.06 μg/ml, irrespective of the resistance genotype. The corresponding values for erythromycin were 61.0% (MICs, ≤0.25 μg/ml) and >64 μg/ml. The erm(B) gene (macrolide-lincosamide-streptogramin B resistance phenotype) was detected in 36.4% (n = 74) of the isolates, which corresponded to 93.6% of erythromycin-intermediate and -resistant isolates, whereas the mef(A) gene (M phenotype [resistance to erythromycin and susceptibility to clindamycin and spiramycin without blunting]) was present in only 2.4% (n = 5) of the isolates. One of the latter isolates also carried erm(B). Interestingly, in one isolate for which the erythromycin MIC was 2 μg/ml, none of these resistance genes could be detected. Erythromycin MICs forS. pneumoniae erm(B)-positive isolates were higher (range, 0.5 to >64 μg/ml) than those for erm(B)- andmef(A)-negative isolates (range, 0.008 to 2 μg/ml). The corresponding values for telithromycin were lower for both groups, with ranges of 0.004 to 1 and 0.002 to 0.06 μg/ml, respectively. The erythromycin MIC was high for a large number oferm(B)-positive isolates, but the telithromycin MIC was low for these isolates. These results indicate the potential usefulness of telithromycin for the treatment of infections caused by erythromycin-susceptible and -resistant S. pneumoniaeisolates when macrolides are indicated.