Pure-glue hidden valleys through the Higgs portal

We consider the possibility that the Higgs boson can act as a link to a hidden sector in the context of pure-glue hidden valley models. In these models the standard model is weakly coupled, through loops of heavy messengers fields, to a hidden sector whose low energy dynamics is described by a pure-Yang-Mills theory. Such a hidden sector contains several metastable hidden glueballs. In this work we shall extend earlier results on hidden valleys to include couplings of the messengers to the standard model Higgs sector. The effective interactions at one-loop couple the hidden gluons to the standard model particles through the Higgs sector. These couplings in turn induce hidden glueball decays to fermion pairs, or cascade decays with multiple Higgs emission. The presence of effective operators of different mass dimensions, often competing with each other, together with a great diversity of states, leads to a great variability in the lifetimes and decay modes of the hidden glueballs. We find that most of the operators considered in this paper are not heavily constrained by precision electroweak physics, therefore leaving plenty of room in the parameter space to be explored by the future experiments at the LHC.Comment: 44 pages, 16 figures. Major revision for JHEP, corrected an error in Eq. 5.1, comments adde

Patterns of mandibular invasion in oral squamous cell carcinoma of the mandibular region

BACKGROUND: Mandibular resections are routinely carried out for achieving a R0 resection for oral cancers. However, the need of mandibular resection to achieve this has always been questioned. The present study was carried out to define the pattern of mandibular involvement in carcinoma of the mandibular region. PATIENTS AND METHODS: A total of 25 consecutive patients who had undergone mandibular resection and were found to have mandibular invasion were studied in a prospective open fashion. After decalcification the specimens were serially sectioned at 1 cm interval to identify invasion of mandibular bone. Type of invasion, route of spread and host cell reactions were also recorded. RESULTS: The mandibular involvement was infiltrative in 14(56%) and erosive in 11(44%). It was cortical in 5(20%), marrow involvement was seen in 15(60%) while 5(20%) had spread through the inferior alveolar canal. Of the 25, 24(96%) lesions were located with in 1 cm of the mandible. CONCLUSION: The possibility of mandibular involvement is higher in patients where tumours are located with in 1 cm of the mandible. Involvement of mandible through the canal of inferior alveolar nerve in the present study was relatively high (20%). Therefore it is recommended that before a decision is taken to preserve the mandible it should be thoroughly screened for possible involvement

Editorial: Observational studies in ADHD: the effects of switching to modified-release methylphenidate preparations on clinical outcomes and adherence

Patients with ADHD may have better adherence to treatment with modified-release methylphenidate (MPH-MR) formulations, which are taken once daily, compared with immediate-release (IR) formulations, which need to be taken several times a day. Data on long-term outcomes such as adherence may be lacking from randomised controlled trials as these are usually only short-term. Observational studies, if performed and reported appropriately, can provide valuable long-term data on such outcomes, as well as additional information on effectiveness and efficiency, from a real-life setting. By reviewing previous observational studies that have investigated switching treatment from MPH-IR to MPH-MR, results from a new, naturalistic observational study, the OBSEER study, are put into context. We conclude that, based on observational trial data, switching from MPH-IR to MPH-MR is a valid clinical approach, with the potential for improved clinical outcome and treatment adherence

Comparing urine samples and cervical swabs for Chlamydia testing in a female population by means of Strand Displacement Assay (SDA)

<p>Abstract</p> <p>Background</p> <p>There has been an increasing number of diagnosed cases of <it>Chlamydia trachomatis </it>in many countries, in particular among young people. The present study was based on a growing request to examine urine as a supplementary or primary specimen in screening for <it>Chlamydia trachomatis </it>in women, with the Becton Dickinson ProbeTec (BDPT) Strand Displacement Assay (SDA). Urine samples may be particularly important in screening young people who are asymptomatic.</p> <p>Methods</p> <p>A total of 603 women aged 15 and older were enrolled from the Sexually Transmitted Infection (STI) clinic at Haukeland University Hospital, Norway, in 2007. Only 31 women were older than 35 years. Cervical swabs and urine samples were tested with BDPT for all participants. In cases of discrepant test results from a given patient, both samples were retested by Cobas TaqManCT and a Polymerase Chain Reaction (PCR)-method (in-house). Prevalence of <it>C. trachomatis</it>, sensitivity, and specificity were estimated by latent class analysis using all test results available. Bootstrap BC confidence intervals (10 000 computations) were estimated for sensitivity and specificity, and their differences in cervix vs. urine tests.</p> <p>Results</p> <p>A total of 1809 specimens were collected from 603 patients. 80 women (13.4%) were positive for <it>C. trachomatis</it>. Among these, BDPT identified 72 and 73 as positive in cervix and urine samples, respectively. Of the 523 <it>C. trachomatis </it>negative women, BDPT identified 519 as negative based on cervical swabs, and 514 based on urine samples. Sensitivity for cervical swabs and urine samples with the BDPT were 89.0% (95% CI 78.8, 98.6) and 90.2% (95% CI 78.1, 95.5), respectively. The corresponding values for specificity were 99.2% (95% CI 98.3, 100) and 98.3% (95% CI 96.4, 100).</p> <p>Conclusions</p> <p>This study indicates that urine specimens are adequate for screening high-risk groups for <it>C. trachomatis </it>by the SDA method (BDPT). Such an approach may facilitate early detection and treatment of the target groups for screening, and be cost-effective for patients and the health services.</p

An observational study of once-daily modified-release methylphenidate in ADHD: quality of life, satisfaction with treatment and adherence

Attention deficit hyperactivity disorder (ADHD) impacts significantly on the quality of life (QoL) of patients and their families. Choice of therapy is increasingly influenced by treatment satisfaction and patient preference, with once-daily modified-release methylphenidate (MPH-MR) formulations offering clear benefits compared with immediate-release (IR) dosage forms. The effects of MPH-MR on QoL in ADHD have not been widely investigated and need more clarity in practice. The open-label OBSEER study evaluated the effectiveness and tolerability of Equasym XL®, a MPH-MR formulation, in routine practice. Children and adolescents (aged 6–17 years) with ADHD and attending school were included if Equasym XL® treatment was planned by the treating physician. Physicians, parents and patients completed questionnaires assessing QoL (KINDL; parent, child or adolescent versions), satisfaction with medication, adherence and treatment tolerability at baseline (Visit 1), 1–3 weeks (Visit 2) and 6–12 weeks (Visit 3) over a maximum 3-month observation period. Data from 822 consecutively referred patients were analysed. QoL and medication satisfaction increased from Visit 1 to Visit 3, with both patients and parents rating therapy with Equasym XL® as better than previous drug therapy. KINDL total score effect sizes were 0.67 (parents’ ratings), 0.52 (children’s ratings) and 0.51 (adolescents’ ratings; all p < 0.001). All KINDL subscores also increased: both parents and patients had the greatest improvement for school. Adherence to Equasym XL® was frequently rated as superior to prior treatment, particularly compared with MPH-IR repeated dosing. Treatment was generally well tolerated; approximately 3% of the patients discontinued treatment due to adverse events. Equasym XL® improved QoL compared with prior therapy, and resulted in good medication satisfaction and adherence in drug-naïve and previously treated patients

[18F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections

Background Management of infection is a major clinical problem. Staphylococcus aureus is a Gram-positive bacterium which colonises approximately one third of the adult human population. Staphylococcal infections can be life-threatening and are frequently complicated by multi-antibiotic resistant strains including methicillin-resistant S. aureus (MRSA). Fluorodeoxyglucose ([18F]FDG) imaging has been used to identify infection sites; however, it is unable to distinguish between sterile inflammation and bacterial load. We have modified [18F]FDG by phosphorylation, producing [18F]FDG-6-P to facilitate specific uptake and accumulation by S. aureus through hexose phosphate transporters, which are not present in mammalian cell membranes. This approach leads to the specific uptake of the radiopharmaceutical into the bacteria and not the sites of sterile inflammation. Methods [18F]FDG-6-P was synthesised from [18F]FDG. Yield, purity and stability were confirmed by RP-HPLC and iTLC. The specificity of [18F]FDG-6-P for the bacterial universal hexose phosphate transporter (UHPT) was confirmed with S. aureus and mammalian cell assays in vitro. Whole body biodistribution and accumulation of [18F]FDG-6-P at the sites of bioluminescent staphylococcal infection were established in a murine foreign body infection model. Results In vitro validation assays demonstrated that [18F]FDG-6-P was stable and specifically transported into S. aureus but not mammalian cells. [18F]FDG-6-P was elevated at the sites of S. aureus infection in vivo compared to uninfected controls; however, the increase in signal was not significant and unexpectedly, the whole-body biodistribution of [18F]FDG-6-P was similar to that of [18F]FDG. Conclusions Despite conclusive in vitro validation, [18F]FDG-6-P did not behave as predicted in vivo. However at the site of known infection, [18F]FDG-6-P levels were elevated compared with uninfected controls, providing a higher signal-to-noise ratio. The bacterial UHPT can transport hexose phosphates other than glucose, and therefore alternative sugars may show differential biodistribution and provide a means for specific bacterial detection

A Possible Role for Metallic Ions in the Carbohydrate Cluster Recognition Displayed by a Lewis Y Specific Antibody

BACKGROUND:Lewis Y (Le(y)) is a blood group-related carbohydrate that is expressed at high surface densities on the majority of epithelial carcinomas and is a promising target for antibody-based immunotherapy. A humanized Le(y)-specific antibody (hu3S193) has shown encouraging safety, pharmacokinetic and tumor-targeting properties in recently completed Phase I clinical trials. METHODOLOGY/PRINCIPAL FINDINGS:We report the three-dimensional structures for both the free (unliganded) and bound (Le(y) tetrasaccharide) hu3S193 Fab from the same crystal grown in the presence of divalent zinc ions. There is no evidence of significant conformational changes occurring in either the Le(y) carbohydrate antigen or the hu3S193 binding site, which suggests a rigid fit binding mechanism. In the crystal, the hu3S193 Fab molecules are coordinated at their protein-protein interface by two zinc ions and in solution aggregation of Fab can be initiated by zinc, but not magnesium ions. Dynamic light scattering revealed that zinc ions could initiate a sharp transition from hu3S193 Fab monomers to large multimeric aggregates in solution. CONCLUSIONS/SIGNIFICANCE:Zinc ions can mediate interactions between hu3S193 Fab in crystals and in solution. Whether metallic ion mediated aggregation of antibody occurs in vivo is not known, but the present results suggest that similar clustering mechanisms could occur when hu3S193 binds to Le(y) on cells, particularly given the high surface densities of antigen on the target tumor cells

Systematic review of quality of life and functional outcomes in randomized placebo-controlled studies of medications for attention-deficit/hyperactivity disorder

Children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) experience functional impairment and poor health-related quality of life (HRQoL) in addition to symptoms of inattention/hyperactivity-impulsivity. To synthesize qualitatively the published evidence from randomized, double-blind, placebo-controlled trials of the effectiveness of pharmacotherapy on functional impairment or HRQoL in patients with ADHD, a systematic PubMed searching and screening strategy was designed to identify journal articles meeting pre-specified criteria. Post hoc analyses and meta-analyses were excluded. HRQoL outcomes, functional outcomes and the principal ADHD symptom-based outcome were extracted from included studies. An effect size of 0.5 versus placebo was used as a threshold for potential clinical relevance (unreported effect sizes were calculated when possible). Of 291 records screened, 35 articles describing 34 studies were included. HRQoL/functioning was usually self-rated in adults and proxy-rated in children/adolescents. Baseline data indicated substantial HRQoL deficits in children/adolescents. Placebo-adjusted effects of medication on ADHD symptoms, HRQoL and functioning, respectively, were statistically or nominally significant in 18/18, 10/12 and 7/9 studies in children/adolescents and 14/16, 9/11 and 9/10 studies in adults. Effect sizes were ≥0.5 versus placebo for symptoms, HRQoL and functioning, respectively, in 14/16, 7/9 and 4/8 studies in children/adolescents; and 6/12, 1/6 and 1/8 studies in adults. Effect sizes were typically larger for stimulants than for non-stimulants, for symptoms than for HRQoL/functioning, and for children/adolescents than for adults. The efficacy of ADHD medication extends beyond symptom control and may help reduce the related but distinct functional impairments and HRQoL deficits in patients with ADHD

Light Sterile Neutrinos and Short Baseline Neutrino Oscillation Anomalies

We study two possible explanations for short baseline neutrino oscillation anomalies, such as the LSND and MiniBooNE anti-neutrino data, and for the reactor anomaly. The first scenario is the mini-seesaw mechanism with two eV-scale sterile neutrinos. We present both analytic formulas and numerical results showing that this scenario could account for the short baseline and reactor anomalies and is consistent with the observed masses and mixings of the three active neutrinos. We also show that this scenario could arise naturally from an effective theory containing a TeV-scale VEV, which could be related to other TeV-scale physics. The minimal version of the mini-seesaw relates the active-sterile mixings to five real parameters and favors an inverted hierarchy. It has the interesting property that the effective Majorana mass for neutrinoless double beta decay vanishes, while the effective masses relevant to tritium beta decay and to cosmology are respectively around 0.2 and 2.4 eV. The second scenario contains only one eV-scale sterile neutrino but with an effective non-unitary mixing matrix between the light sterile and active neutrinos. We find that though this may explain the anomalies, if the non-unitarity originates from a heavy sterile neutrino with a large (fine-tuned) mixing angle, this scenario is highly constrained by cosmological and laboratory observations.Comment: 25 pages, 6 figure