First Simultaneous Determination of Inclusive and Exclusive |V_{ub}|.

The first simultaneous determination of the absolute value of the Cabibbo-Kobayashi-Maskawa matrix element V_{ub} using inclusive and exclusive decays is performed with the full Belle data set at the ϒ(4S) resonance, corresponding to an integrated luminosity of 711 fb^{-1}. We analyze collision events in which one B meson is fully reconstructed in hadronic modes. This allows for the reconstruction of the hadronic X_{u} system of the semileptonic b→uℓν[over ¯]_{ℓ} decay. We separate exclusive B→πℓν[over ¯]_{ℓ} decays from other inclusive B→X_{u}ℓν[over ¯]_{ℓ} and backgrounds with a two-dimensional fit that utilizes the number of charged pions in the X_{u} system and the four-momentum transfer q^{2} between the B and X_{u} systems. Combining our measurement with information from lattice QCD and QCD calculations of the inclusive partial rate as well as external experimental information on the shape of the B→πℓν[over ¯]_{ℓ} form factor, we determine |V_{ub}^{excl}|=(3.78±0.23±0.16±0.14)×10^{-3} and |V_{ub}^{incl}|=(3.88±0.20±0.31±0.09)×10^{-3}, respectively, with the uncertainties being the statistical error, systematic errors, and theory errors. The ratio of |V_{ub}^{excl}|/|V_{ub}^{incl}|=0.97±0.12 is compatible with unity.

Search for a Heavy Neutrino in τ Decays at Belle.

We report on a search for a heavy Majorana neutrino in the decays τ^{-}→π^{-}ν_{h}, ν_{h}→π^{±}ℓ^{∓}, ℓ=e, µ. The results are obtained using the full data sample of 988 fb^{-1} collected with the Belle detector at the KEKB asymmetric energy e^{+}e^{-} collider, which contains 912×10^{6} ττ pairs. We observe no significant signal and set 95% CL upper limits on the couplings of the heavy right-handed neutrinos to the conventional standard model left-handed neutrinos in the mass range 0.2-1.6 GeV/c^{2}. This is the first study of a mixed couplings of heavy neutrinos to τ leptons and light-flavor leptons.

Search for the Lepton Flavor Violating Decays B

We present a search for the lepton flavor violating decays B^{+}→K^{+}τ^{±}ℓ^{∓}, with ℓ=(e,µ), using the full data sample of 772×10^{6} BB[over ¯] pairs recorded by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We use events in which one B meson is fully reconstructed in a hadronic decay mode. We find no evidence for B^{±}→K^{±}τℓ decays and set upper limits on their branching fractions at the 90% confidence level in the (1-3)×10^{-5} range. The obtained limits are the world's best results.

First Measurement of the Michel Parameter ξ

We report the first measurement of the Michel parameter ξ^{'} in the τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} decay with a new method proposed just recently. The measurement is based on the reconstruction of the τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} events with subsequent muon decay in flight in the Belle central drift chamber. The analyzed data sample of 988 fb^{-1} collected by the Belle detector corresponds to approximately 912×10^{6} τ^{+}τ^{-} pairs. We measure ξ^{'}=0.22±0.94(stat)±0.42(syst), which is in agreement with the standard model prediction of ξ^{'}=1. Statistical uncertainty dominates in this study, being a limiting factor, while systematic uncertainty is well under control. Our analysis proved the practicability of this promising method and its prospects for further precise measurement in future experiments.

First Measurement of the B

We study B^{+}→π^{+}π^{0}π^{0} using 711 fb^{-1} of data collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We measure an inclusive branching fraction of (19.0±1.5±1.4)×10^{-6} and an inclusive CP asymmetry of (9.2±6.8±0.7)%, where the first uncertainties are statistical and the second are systematic, and a B^{+}→ρ(770)^{+}π^{0} branching fraction of (11.2±1.1±0.9_{-1.6}^{+0.8})×10^{-6}, where the third uncertainty is due to possible interference with B^{+}→ρ(1450)^{+}π^{0}. We present the first observation of a structure around 1 GeV/c^{2} in the π^{0}π^{0} mass spectrum, with a significance of 6.4σ, and measure a branching fraction to be (6.9±0.9±0.6)×10^{-6}. We also report a measurement of local CP asymmetry in this structure.

Case report: Gastroenterological management in a case of cardio-facio-cutaneous syndrome.

Background: cardio-facio-cutaneous syndrome is a rare genetic disorder affecting less than 900 people in the world. It is mainly characterized by craniofacial, dermatologic and cardiac defects, but also gastroenterological symptoms may be present, ranging from feeding difficulties to gastroesophageal reflux and constipation.In this report we describe a case of this syndrome characterized by severe feeding and growth difficulties, with a particular focus on the management of gastroenterological complications. Case presentation: the patient was a caucasian male affected by Cardio-Facio-Cutaneous syndrome who presented feeding difficulties already a few hours after birth. These symptoms worsened in the following months and lead to a complete growth arrest and malnutrition. He was first treated with a nasogastric tube placement. Subsequently, a laparoscopic Nissen fundoplication and a laparoscopic Stamm gastrostomy were performed. The child was fed with nocturnal enteral nutrition and diurnal oral and enteral nutrition. Eventually the patient resumed feeding validly and regained adequate growth. Conclusion: this paper aims to bring to light a complex rare syndrome that infrequently comes to the attention of the pediatricians and whose diagnosis is not always straightforward. We also highlight the possible complications under a gastroenterologic point of view. Our contribution can be helpful to the pediatrician in the first diagnostic suspect of this syndrome. In particular, it is worth highlighting that -in an infant with Noonan-like features- symptoms like suction or swallowing problems, vomiting and feeding difficulties should orient towards the diagnosis of a Cardio-facio-cutaneous syndrome. It is also important to stress that its related gastroenterological issues may lead to severe growth failure and therefore the role of the gastroenterologist is key to manage supplemental feeding and to establish whether a nasogastric or gastrostomic tube placement is necessary.

First Observation of Λπ

Using the data sample of 980 fb^{-1} collected with the Belle detector operating at the KEKB asymmetric-energy e^{+}e^{-} collider, we present the results of an investigation of the Λπ^{+} and Λπ^{-} invariant mass distributions looking for substructure in the decay Λ_{c}^{+}→Λπ^{+}π^{+}π^{-}. We find a significant signal in each mass distribution. When interpreted as resonances, we find for the Λπ^{+} (Λπ^{-}) combination a mass of 1434.3±0.6(stat)±0.9(syst) MeV/c^{2} [1438.5±0.9(stat)±2.5(syst) MeV/c^{2}], an intrinsic width of 11.5±2.8(stat)±5.3(syst) MeV/c^{2} [33.0±7.5(stat)±23.6(syst) MeV/c^{2}] with a significance of 7.5σ (6.2σ). As these two signals are very close to the K[over ¯]N threshold, we also investigate the possibility of a K[over ¯]N cusp, and find that we cannot discriminate between these two interpretations due to the limited size of the data sample.

Measurement of Two-Particle Correlations of Hadrons in e

The measurement of two-particle angular correlation functions in high-multiplicity e^{+}e^{-} collisions at sqrt[s]=10.52 GeV is reported. In this study, the 89.5 fb^{-1} of hadronic e^{+}e^{-} annihilation data collected by the Belle detector at KEKB are used. Two-particle angular correlation functions are measured in the full relative azimuthal angle (Δϕ) and three units of pseudorapidity (Δη), defined by either the electron beam axis or the event-shape thrust axis, and are studied as a function of charged-particle multiplicity. The measurement in the thrust axis analysis, with mostly outgoing quark pairs determining the reference axis, is sensitive to the region of additional soft gluon emissions. No significant anisotropic collective behavior is observed with either coordinate analyses. Near-side jet correlations appear to be absent in the thrust axis analysis. The measurements are compared to predictions from various event generators and are expected to provide new constraints to the phenomenological models in the low-energy regime.

Search for a Light Higgs Boson in Single-Photon Decays of ϒ(1S) Using ϒ(2S)→π

We search for a light Higgs boson (A^{0}) decaying into a τ^{+}τ^{-} or µ^{+}µ^{-} pair in the radiative decays of ϒ(1S). The production of ϒ(1S) mesons is tagged by ϒ(2S)→π^{+}π^{-}ϒ(1S) transitions, using 158×10^{6} ϒ(2S) events accumulated with the Belle detector at the KEKB asymmetric energy electron-positron collider. No significant A^{0} signals in the mass range from the τ^{+}τ^{-} or µ^{+}µ^{-} threshold to 9.2 GeV/c^{2} are observed. We set the upper limits at 90% credibility level (C.L.) on the product branching fractions for ϒ(1S)→γA^{0} and A^{0}→τ^{+}τ^{-} varying from 3.8×10^{-6} to 1.5×10^{-4}. Our results represent an approximately twofold improvement on the current world best upper limits for the ϒ(1S)→γA^{0}(→τ^{+}τ^{-}) production. For A^{0}→µ^{+}µ^{-}, the upper limits on the product branching fractions for ϒ(1S)→γA^{0} and A^{0}→µ^{+}µ^{-} are at the same level as the world average limits, and vary from 3.1×10^{-7} to 1.6×10^{-5}. The upper limits at 90% credibility level on the Yukawa coupling f_{ϒ(1S)} and mixing angle sinθ_{A^{0}} are also given.

Systemic corticosteroids could be used as bridge treatment in children with obstructive sleep apnea syndrome waiting for surgery.

PURPOSE: Local and systemic inflammatory markers and pro-inflammatory cytokines are increased in children with obstructive sleep apnea syndrome (OSAS). Therefore, systemic or topical anti-inflammatory agents are used to treat this syndrome. We evaluated the treatment with systemic corticosteroids in children with severe OSAS and adenotonsillar hypertrophy before surgery. METHODS: This was an unblinded open label study. Children with severe OSAS (diagnosed through polysomnography, obstructive apnea-hypopnea index [AHI] > 10 eV/h) were recruited. Exclusion criteria included age < 3 years, history of acute or chronic cardiorespiratory or neuromuscular or metabolic disease; major craniofacial abnormalities; and chromosomal syndromes and epilepsy. Computer-generated random numbers were used for simple randomization of subjects. All children were treated with intranasal beclomethasone spray, and 15 children additionally received oral betamethasone and 0.1 mg/kg per day for 7 days. Sleep clinical record (SCR) and pulsoximetry were performed before and after 7 days in all children. RESULTS: Among 28 children with severe OSAS mean age was 4.5 ± 1.8 years, AHI 20.4 ± 1.8 eV/h). In children treated with intranasal and oral corticosteroids, mean (95.3 ± 1.1 vs 97.0 ± 0.8%, p = 0.0001) and minimum oxygen saturation (78.8 ± 6.3 vs 89.2 ± 4.2, p = 0.001) improved, and the SCR score (12.6 ± 1.2 vs 8.3 ± 1.1, p = 0.0001) was reduced. Children treated only with intranasal beclomethasone spray showed no differences in outcome measures before and after treatments. When we considered the oximetry measures, after corticosteroid treatment, we obtained statistical differences between the 2 groups (p < 0.01). CONCLUSIONS: These results seem to suggest that a short course of oral betamethasone could be useful to treat children with severe OSAS and adenotonsillar hypertrophy waiting for surgery.

Measurements of the Branching Fractions of the Semileptonic Decays Ξ_{c}

Using data samples of 89.5 and 711 fb^{-1} recorded at energies of sqrt[s]=10.52 and 10.58 GeV, respectively, with the Belle detector at the KEKB e^{+}e^{-} collider, we report measurements of branching fractions of semileptonic decays Ξ_{c}^{0}→Ξ^{-}ℓ^{+}ν_{ℓ} (ℓ=e or µ) and the CP-asymmetry parameter of Ξ_{c}^{0}→Ξ^{-}π^{+} decay. The branching fractions are measured to be B(Ξ_{c}^{0}→Ξ^{-}e^{+}ν_{e})=(1.31±0.04±0.07±0.38)% and B(Ξ_{c}^{0}→Ξ^{-}µ^{+}ν_{µ})=(1.27±0.06±0.10±0.37)%, and the decay parameter α_{Ξπ} is measured to be 0.63±0.03±0.01 with much improved precision compared with the current world average. The corresponding ratio B(Ξ_{c}^{0}→Ξ^{-}e^{+}ν_{e})/B(Ξ_{c}^{0}→Ξ^{-}µ^{+}ν_{µ}) is 1.03±0.05±0.07, which is consistent with the expectation of lepton flavor universality. The first measured asymmetry parameter A_{CP}=(α_{Ξ^{-}π^{+}}+α_{Ξ[over ¯]^{+}π^{-}})/(α_{Ξ^{-}π^{+}}-α_{Ξ[over ¯]^{+}π^{-}})=0.024±0.052±0.014 is found to be consistent with zero. The first and the second uncertainties above are statistical and systematic, respectively, while the third ones arise due to the uncertainty of the Ξ_{c}^{0}→Ξ^{-}π^{+} branching fraction.

Test of Lepton-Flavor Universality in B→K

We present a measurement of R_{K^{*}}, the branching fraction ratio B(B→K^{*}µ^{+}µ^{-})/B(B→K^{*}e^{+}e^{-}), for both charged and neutral B mesons. The ratio for the charged case R_{K^{*+}} is the first measurement ever performed. In addition, we report absolute branching fractions for the individual modes in bins of the squared dilepton invariant mass q^{2}. The analysis is based on a data sample of 711 fb^{-1}, containing 772×10^{6} BB[over ¯] events, recorded at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The obtained results are consistent with standard model expectations.

Evidence for X(3872)→J/ψπ

We report the first evidence for X(3872) production in two-photon interactions by tagging either the electron or the positron in the final state, exploring the highly virtual photon region. The search is performed in e^{+}e^{-}→e^{+}e^{-}J/ψπ^{+}π^{-}, using 825 fb^{-1} of data collected by the Belle detector operated at the KEKB e^{+}e^{-} collider. We observe three X(3872) candidates, where the expected background is 0.11±0.10 events, with a significance of 3.2σ. We obtain an estimated value for Γ[over ˜]_{γγ}B(X(3872)→J/ψπ^{+}π^{-}) assuming the Q^{2} dependence predicted by a cc[over ¯] meson model, where -Q^{2} is the invariant mass squared of the virtual photon. No X(3915)→J/ψπ^{+}π^{-} candidates are found.

Measurement of R(D) and R(D

The experimental results on the ratios of branching fractions R(D)=B(B[over ¯]→Dτ^{-}ν[over ¯]_{τ})/B(B[over ¯]→Dℓ^{-}ν[over ¯]_{ℓ}) and R(D^{*})=B(B[over ¯]→D^{*}τ^{-}ν[over ¯]_{τ})/B(B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ}), where ℓ denotes an electron or a muon, show a long-standing discrepancy with the standard model predictions, and might hint at a violation of lepton flavor universality. We report a new simultaneous measurement of R(D) and R(D^{*}), based on a data sample containing 772×10^{6} BB[over ¯] events recorded at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. In this analysis the tag-side B meson is reconstructed in a semileptonic decay mode and the signal-side τ is reconstructed in a purely leptonic decay. The measured values are R(D)=0.307±0.037±0.016 and R(D^{*})=0.283±0.018±0.014, where the first uncertainties are statistical and the second are systematic. These results are in agreement with the standard model predictions within 0.2, 1.1, and 0.8 standard deviations for R(D), R(D^{*}), and their combination, respectively. This work constitutes the most precise measurements of R(D) and R(D^{*}) performed to date as well as the first result for R(D) based on a semileptonic tagging method.

LKB1 loss is associated with glutathione deficiency under oxidative stress and sensitivity of cancer cells to cytotoxic drugs and γ-irradiation.

The liver kinase B1 (LKB1) gene is a tumor suppressor associated with the hereditary Peutz-Jeghers syndrome and frequently mutated in non-small cell lung cancer and in cervical cancer. Previous studies showed that the LKB1/AMPK axis is involved in regulation of cell death and survival under metabolic stress. By using isogenic pairs of cancer cell lines, we report here that the genetic loss of LKB1 was associated with increased intracellular levels of total choline containing metabolites and, under oxidative stress, it impaired maintenance of glutathione (GSH) levels. This resulted in markedly increased intracellular reactive oxygen species (ROS) levels and sensitivity to ROS-induced cell death. These effects were rescued by re-expression of LKB1 or pre-treatment with the anti-oxidant and GSH replenisher N-acetyl cysteine. This role of LKB1 in response to ROS-inducing agents was largely AMPK-dependent. Finally, we observed that LKB1 defective cells are highly sensitive to cisplatin and γ-irradiation in vitro, suggesting that LKB1 mutated tumors could be targeted by oxidative stress-inducing therapies.

Chronic intestinal pseudo-obstruction: Progress in management?

Chronic intestinal pseudo-obstruction (CIPO) is a severe form of gastrointestinal dysmotility (often due to derangement of the innervation/smooth muscle/interstitial cells of Cajal) with recurrent episodes of intestinal subocclusion mimicking a mechanical obstruction. Because of its complexity and heterogeneity, CIPO is often misdiagnosed or remains unrecognized until advanced stages. Management is a critical aspect in CIPO patient care. So far, most prokinetic drugs have not proven efficacy in restoring intestinal propulsion, thus nutritional support, fluid/electrolyte replacement, and antibiotics are the mainstay of treatment. In this issue of the journal, Ohkubo et al showed promising data indicating that percutaneous endoscopic gastro-jejunostomy (PEG-J) can be proposed as a measure for intestinal decompression, thereby improving CIPO-associated abdominal symptoms, including pain. In addition to a concise update of clinical and diagnostic features, the present minireview tackles management options, with a major emphasis on PEG-J, for CIPO patients.

Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) represents the most severe form of gastrointestinal dysmotility with debilitating and potentially lethal consequences. Symptoms can be non-specific, and result in this condition being diagnosed incorrectly or too late with consequences for morbidity and even mortality. PURPOSE: The present article aims to provide pediatric and adult gastroenterologists with an up to date review about clinical features, diagnosis and therapeutic options for CIPO. Although pediatric and adult CIPO share many clinical aspects distinctive features can be identified. There is no single diagnostic test or pathognomonic finding of CIPO, thus a stepwise approach including radiology, endoscopy, laboratory, manometry, and histopathology should be considered in the diagnostic work-up. Treatment of patients with CIPO is challenging and requires a multidisciplinary effort with participation of appropriately experienced gastroenterologists, pathologists, dieticians, surgeons, psychologists, and other subspecialists based on the presence of comorbidities. Current treatment options invariably involve surgery and specialized nutritional support, especially in children. Medical therapies are mainly aimed to avoid complications such as sepsis or intestinal bacterial overgrowth and, where possible, restore intestinal propulsion. More efficacious therapeutic options are eagerly awaited for such difficult patients.

Neuroimmune interactions at different intestinal sites are related to abdominal pain symptoms in children with IBS.

BACKGROUND: Neuroimmune interactions and inflammation have been proposed as factors involved in sensory-motor dysfunction and symptom generation in adult irritable bowel syndrome (IBS) patients. In children with IBS and healthy controls, we measured ileocolonic mast cell infiltration and fecal calprotectin and evaluated the relationships between these parameters and abdominal pain symptoms and stooling pattern. METHODS: Irritable bowel syndrome patients diagnosed according to Pediatric Rome III criteria and healthy controls kept a 2-week pain/stooling diary. Ileocolonic mucosal mast cells (MC) and MC in close proximity to nerve fibers (MC-NF) were identified immunohistochemically and quantified. Fecal calprotectin concentration was measured. KEY RESULTS: 21 IBS patients and 10 controls were enrolled. The MC-NF count was significantly higher in the ileum (p = 0.01), right colon (p = 0.04), and left colon (p < 0.001) of IBS patients compared with controls. No differences in fecal calprotectin concentration were noted. Abdominal pain intensity score correlated with ileal MC count (r(s) = 0.47, p = 0.030) and right colon MC-NF count (r(s) = 0.52, p = 0.015). In addition, children with IBS with >3 abdominal pain episodes/week had greater ileal (p = 0.002) and right colonic (p = 0.01) MC counts and greater ileal (p = 0.05) and right colonic (p = 0.016) MC-NF counts than children with less frequent pain. No relationship was found between MC and MC-NF and fecal calprotectin or stooling pattern. CONCLUSIONS & INFERENCES: Mast cells-nerve fibers counts are increased in the ileocolonic mucosa of children with IBS. Mast cells and MC-NF counts are related to the intensity and frequency of abdominal pain.

Size and dynamics of mucosal and peripheral IL-17A+ T-cell pools in pediatric age, and their disturbance in celiac disease.

Mucosal interleukin (IL)-17A-producing T cells contribute to protective antimicrobial responses and to epithelial barrier integrity; their role in celiac disease (CD) is debated. We analyzed the frequency and developmental dynamics of mucosal (intraepithelial lymphocytes (IEL)) and circulating (peripheral blood (PB)) IL-17A (T17) and/or interferon (IFN)-γ-producing (T1, T1/T17) T-cell populations in 86 pediatric controls and 116 age-matched CD patients upon phorbol myristate acetate/ionomycin or CD3/CD28 stimulation. T17 and T1/17 are physiologically present among IEL and PB populations, and their frequency is selectively and significantly reduced in CD IEL. The physiological age-dependent increase of Th17 IEL is also absent in CD, while IFN-γ-producing PB-T cells significantly accumulate with patient's age. Finally, the amplitude of IL-17A+ and IFN-γ+ T-cell pools are significantly correlated in different individuals; this relationship only applies to CD4+ T cells in controls, while it involves also the CD4- counterpart in CD patients. In conclusion, both size and dynamics of mucosa-associated and circulating IL-17A+ T-cell pools are finely regulated in human pediatric subjects, and severely disturbed in CD. The impaired IL-17A+ IEL-T pool may negatively impact on epithelial barrier efficiency, and contribute to CD mucosa damage; the disturbed dynamics of circulating IL-17A+ and IFN-γ+ T-cell pools may be involved in the extraintestinal autoimmune manifestations associated with CD.

Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis.

BACKGROUND: Intestinal microbiota manipulation, one of the pathogenetic components of inflammatory bowel disease (IBD), has become an attractive therapy for ulcerative colitis (UC). AIM: To assess in children with active distal UC the effectiveness of Lactobacillus (L) reuteri ATCC 55730 enema on inflammation and cytokine expression of rectal mucosa. METHODS: A total of 40 patients (median age: 7.2 years range 6-18) with mild to moderate UC were enrolled in a prospective, randomised, placebo-controlled study. They received an enema solution containing 10(10) CFU of L. reuteri ATCC 55730 or placebo for 8 weeks, in addition to oral mesalazine. Clinical endoscopic and histological scores as well as rectal mucosal expression levels of IL-10, IL-1ß, TNFα and IL-8 were evaluated at the beginning and at the end of the trial. RESULTS: Thirty-one patients accomplished the trial (17 males, median age 13 year, range 7-18). Mayo score (including clinical and endoscopic features) decreased significantly in the L. reuteri group (3.2 ± 1.3 vs. 8.6 ± 0.8, P < 0.01) compared with placebo (7.1 ± 1.1 vs. 8.7 ± 0.7, NS); furthermore, histological score significantly decrease only in the L. reuteri group (0.6 ± 0.5 vs. 4.5 ± 0.6, P < 0.01) (placebo: 2.9 ± 0.8 vs. 4.6 ± 0.6, NS). At the post-trial evaluation of cytokine mucosal expression levels, IL-10 significantly increased (P < 0.01) whereas IL-1ß, TNFα and IL-8 significantly decreased (P < 0.01) only in the L. reuteri group. CONCLUSIONS: In children with active distal ulcerative colitis, rectal infusion of L. reuteri is effective in improving mucosal inflammation and changing mucosal expression levels of some cytokines involved in the mechanisms of inflammatory bowel disease.