A Multicentric, Retrospective, Real-world Study on Immune-related Adverse Events in Patients with Advanced Non-small Cell Lung Cancers Treated with Pembrolizumab Monotherapy.

AIMS: We present 7 years of clinical experience with single-agent pembrolizumab immune checkpoint inhibitor immunotherapy in non-small cell lung cancers (NSCLC) from four UK cancer centres. MATERIALS AND METHODS: This multi-institutional retrospective cohort study included 226 metastatic NSCLC patients. Outcomes were number and severity of immune-related adverse events (irAEs), median progression-free survival (mPFS) and median overall survival (mOS). RESULTS: Within our cohort, 119/226 (53%) patients developed irAEs. Of these, 54/119 (45%) experienced irAEs affecting two or more organ systems. The most common irAEs were diarrhoea and rash. The development of an irAE was associated with better mOS (20.7 versus 8.0 months; P < 0.001) and mPFS (12.0 versus 3.9 months; P < 0.001). The development of grade 3/4 toxicities was associated with worse outcomes compared with the development of grade 1/2 toxicities (mOS 6.1 months versus 25.2 months, P < 0.01; mPFS 5.6 months versus 19.3 months, P = 0.01, respectively). Females had a higher proportion of reported grade 3/4 toxicities (13/44 [29.5%] versus 10/74 [13.5%], P = 0.03). Using a multiple Cox regression model, the presence of irAEs was associated with a better overall survival (hazard ratio = 0.42, 95% confidence interval 0.29-0.61; P < 0.01) and better PFS (hazard ratio 0.38, 95% confidence interval 0.27-0.53; P < 0.001). CONCLUSION: In this multicentre retrospective cohort study, the development of at least one irAE was associated with significantly longer mPFS and mOS; however, more severe grade 3 and 4 irAEs were associated with worse outcomes. Delayed-onset irAEs, after the 3-month timepoint, were associated with better clinical outcomes.

Design and testing of a high perveance sheet beam electron gun.

This paper presents the design, prototype engineering, and initial testing of a relatively low-voltage, high aspect ratio electron gun for versatile pulsed power applications. The sheet beam, diode electron gun is designed for (23-25) kV voltage and 6 µA/V1.5, as is required for x-band klystron, as a part of a compact Klylac delivering electron beam energy in the MeV range. The gun prototype was engineered, built, and tested using a Scandinova M1-0.5 modulator. Beam loss on the anode aperture is evaluated from transient waveforms and equivalent circuit modeling.

Search for Evidence of Baryogenesis and Dark Matter in B

A new dark sector antibaryon, denoted ψ_{D}, could be produced in decays of B mesons. This Letter presents a search for B^{+}→ψ_{D}+p (and the charge conjugate) decays in e^{+}e^{-} annihilations at 10.58 GeV, using data collected in the BABAR experiment. Data corresponding to an integrated luminosity of 398 fb^{-1} are analyzed. No evidence for a signal is observed. Branching fraction upper limits in the range from 10^{-7}-10^{-5} are obtained at 90% confidence level for masses of 1.0

Analgesic dorsal root ganglion field stimulation blocks both afferent and efferent spontaneous activity in sensory neurons of rats with monosodium iodoacetate-induced osteoarthritis.

OBJECTIVES: Chronic joint pain is common in patients with osteoarthritis (OA). Non-steroidal anti-inflammatory drugs and opioids are used to relieve OA pain, but they are often inadequately effective. Dorsal root ganglion field stimulation (GFS) is a clinically used neuromodulation approach, although it is not commonly employed for patients with OA pain. GFS showed analgesic effectiveness in our previous study using the monosodium iodoacetate (MIA) - induced OA rat pain model. This study was to evaluate the mechanism of GFS analgesia in this model. METHODS: After osteoarthritis was induced by intra-articular injection of MIA, pain behavioral tests were performed. Effects of GFS on the spontaneous activity (SA) were tested with in vivo single-unit recordings from teased fiber saphenous nerve, sural nerve, and dorsal root. RESULTS: Two weeks after intra-articular MIA injection, rats developed pain-like behaviors. In vivo single unit recordings from bundles teased from the saphenous nerve and third lumbar (L3) dorsal root of MIA-OA rats showed a higher incidence of SA than those from saline-injected control rats. GFS at the L3 level blocked L3 dorsal root SA. MIA-OA reduced the punctate mechanical force threshold for inducing AP firing in bundles teased from the L4 dorsal root, which reversed to normal with GFS. After MIA-OA, there was increased retrograde SA (dorsal root reflex), which can be blocked by GFS. CONCLUSIONS: These results indicate that GFS produces analgesia in MIA-OA rats at least in part by producing blockade of afferent inputs, possibly also by blocking efferent activity from the dorsal horn.

Search for an Axionlike Particle in B Meson Decays.

Axionlike particles (ALPs) are predicted in many extensions of the standard model, and their masses can naturally be well below the electroweak scale. In the presence of couplings to electroweak bosons, these particles could be emitted in flavor-changing B meson decays. We report herein a search for an ALP, a, in the reaction B^{±}→K^{±}a, a→γγ using data collected by the BABAR experiment at SLAC. No significant signal is observed, and 90% confidence level upper limits on the ALP coupling to electroweak bosons are derived as a function of ALP mass, improving current constraints by several orders of magnitude in the range 0.175 GeV

Update on the Recommendations on Breast Cancer Screening by the Cancer Expert Working Group on Cancer Prevention and Screening.

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population: Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening. A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

Search for Lepton Flavor Violation in ϒ(3S)→e

We report on the first search for electron-muon lepton flavor violation (LFV) in the decay of a b quark and b antiquark bound state. We look for the LFV decay ϒ(3S)→e^{±}µ^{∓} in a sample of 118 million ϒ(3S) mesons from 27 fb^{-1} of data collected with the BABAR detector at the SLAC PEP-II e^{+}e^{-} collider operating with a 10.36 GeV center-of-mass energy. No evidence for a signal is found, and we set a limit on the branching fraction B[ϒ(3S)→e^{±}µ^{∓}]<3.6×10^{-7} at 90% C. L. This result can be interpreted as a limit Λ_{NP}/g_{NP}^{2}>80 TeV on the energy scale Λ_{NP} divided by the coupling-squared g_{NP}^{2} of relevant new physics (NP).

Search for Darkonium in e

Collider searches for dark sectors, new particles interacting only feebly with ordinary matter, have largely focused on identifying signatures of new mediators, leaving much of dark sector structures unexplored. In particular, the existence of dark matter bound states (darkonia) remains to be investigated. This possibility could arise in a simple model in which a dark photon (A^{'}) is light enough to generate an attractive force between dark fermions. We report herein a search for a J^{PC}=1^{--} darkonium state, the ϒ_{D}, produced in the reaction e^{+}e^{-}→γϒ_{D}, ϒ_{D}→A^{'}A^{'}A^{'}, where the dark photons subsequently decay into pairs of leptons or pions, using 514 fb^{-1} of data collected with the BABAR detector. No significant signal is observed, and we set bounds on the γ-A^{'} kinetic mixing as a function of the dark sector coupling constant for 0.001

[Quality evaluation of Gastrodiae Rhizoma standard decoction based on UPLC fingerprint and quantitative analysis multi-components method].

To establish the quantitative analysis multi-components with a single-marker(QAMS) method for six components and fingerprint of standard decoction of Gastrodiae Rhizoma, verify the accuracy and feasibility of the method, and evaluate the quality of standard decoction. Based on UPLC with gastrodin as the internal standard, relative correction factors of p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C, parishin A and gastrodin were determined by investigating the column temperature, flow rate, chromatographic columns and multi-point concentration correction. The total contents in 18 batches of standard decoction of Gastrodiae Rhizoma and the similarity were determined to calculate the similarity. The results of standard curve method, external standard one-point method and quantitative analysis multi-components with a single-marker(QAMS) were compared, and the results showed that there was no significant difference among these three methods. By analyzing the results of standard decoctions from different origins, it can be seen that the quality of Gastrodia standard decoctions derived from Anhui and Yunnan was better, followed by Shaanxi and Hubei, and relatively poor in Gansu, with similarities all above 0.90 in the fingerprints. Therefore, the QAMS method that can measure the contents of gastrodin, p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C and parishin A in standard decoction of Gastrodiae Rhizoma combined with fingerprint is accurate, feasible and fast, which can be used to evaluate the quality of standard decoction of Gastrodiae Rhizoma, and also provide a reference for the research on the quality standards of raw materials for Gastrodiae Rhizoma prepared slices and alike.

Search for a Dark Leptophilic Scalar in e

Many scenarios of physics beyond the standard model predict the existence of new gauge singlets, which might be substantially lighter than the weak scale. The experimental constraints on additional scalars with masses in the MeV to GeV range could be significantly weakened if they interact predominantly with leptons rather than quarks. At an e^{+}e^{-} collider, such a leptophilic scalar (ϕ_{L}) would be produced predominantly through radiation from a τ lepton. We report herein a search for e^{+}e^{-}→τ^{+}τ^{-}ϕ_{L}, ϕ_{L}→ℓ^{+}ℓ^{-} (ℓ=e, µ) using data collected by the BABAR experiment at SLAC. No significant signal is observed, and we set limits on the ϕ_{L} coupling to leptons in the range 0.04

Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics.

A fundamental, clinical, and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question, because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin, detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR (qPCR) for V. cholerae (n = 78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (odds ratio [OR], 0.108; 95% confidence interval [CI], 0.002 to 0.872) and 87% (OR, 0.130; 95% CI, 0.022 to 0.649), respectively, when lytic bacteriophage were detected. The odds that an RDT or qPCR was positive was reduced by more than 99% (OR, 0.00; 95% CI, 0.00 to 0.28) and 89% (OR, 0.11; 95% CI, 0.03 to 0.44), respectively, when azithromycin was detected. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as a proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation.

Measurements of the Absolute Branching Fractions of B

A study of the two-body decays B^{±}→X_{cc[over ¯]}K^{±}, where X_{cc[over ¯]} refers to one charmonium state, is reported by the BABAR Collaboration using a data sample of 424 fb^{-1}. The absolute determination of branching fractions for these decays are significantly improved compared to previous BABAR measurements. Evidence is found for the decay B^{+}→X(3872)K^{+} at the 3σ level. The absolute branching fraction B[B^{+}→X(3872)K^{+}]=[2.1±0.6(stat)±0.3(syst)]×10^{-4} is measured for the first time. It follows that B[X(3872)→J/ψπ^{+}π^{-}]=(4.1±1.3)%, supporting the hypothesis of a molecular component for this resonance.

Thermionic microwave gun for terahertz and synchrotron light sources.

Conventional thermionic microwave and radio frequency (RF) guns can offer high average beam current, which is important for synchrotron light and terahertz (THz) radiation source facilities, as well as for industrial applications. For example, the Advanced Photon Source at Argonne National Laboratory is a national synchrotron-radiation light source research facility that utilizes thermionic RF guns. However, these existing thermionic guns are bulky, difficult to handle and install, easily detuned, very sensitive to thermal expansion, and due for a major upgrade and replacement. In this paper, we present the design of a new, more stable, and reliable gun with optimized electromagnetic performance, improved thermal engineering, and a more robust cathode mounting technique, which is a critical step to improve the performance of existing and future light sources, industrial accelerators, and electron beam-driven THz sources. We will also present a fabricated gun prototype and show results of high-power and beam tests.

Search for Rare or Forbidden Decays of the D

We present a search for nine lepton-number-violating and three lepton-flavor-violating neutral charm decays of the type D^{0}→h^{'-}h^{-}ℓ^{'+}ℓ^{+} and D^{0}→h^{'-}h^{+}ℓ^{'±}ℓ^{∓}, where h and h^{'} represent a K or π meson and ℓ and ℓ^{'} an electron or muon. The analysis is based on 468 fb^{-1} of e^{+}e^{-} annihilation data collected at or close to the ϒ(4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory. No significant signal is observed for any of the twelve modes, and we establish 90% confidence level upper limits on the branching fractions in the range (1.0-30.6)×10^{-7}. The limits are between 1 and 3 orders of magnitude more stringent than previous measurements.

Precision Measurement of the Ratio B(ϒ(3S)→τ

We report on a precision measurement of the ratio R_{τµ}^{ϒ(3S)}=B(ϒ(3S)→τ^{+}τ^{-})/B(ϒ(3S)→µ^{+}µ^{-}) using data collected with the BABAR detector at the SLAC PEP-II e^{+}e^{-} collider. The measurement is based on a 28 fb^{-1} data sample collected at a center-of-mass energy of 10.355 GeV corresponding to a sample of 122 million ϒ(3S) mesons. The ratio is measured to be R_{τµ}^{ϒ(3S)}=0.966±0.008_{stat}±0.014_{syst} and is in agreement with the standard model prediction of 0.9948 within 2 standard deviations. The uncertainty in R_{τµ}^{ϒ(3S)} is almost an order of magnitude smaller than the only previous measurement.

Family medicine vocational training and career satisfaction in Hong Kong.

BACKGROUND: Postgraduate vocational training in family medicine (FM) is essential for physicians to build capacity and develop quality primary care. Inadequate standards in training and curriculum development can contribute to poor recruitment and retention of doctors in primary care. This study aimed to investigate: 1) the satisfaction level of doctors regarding vocational training in family medicine and associated demographics; and 2) the satisfaction level of doctors regarding their family medicine career and associated factors. METHOD: This is a cross sectional study of all family medicine physicians across all government-funded primary care clinics (GOPCs). The study questionnaire consisted of items from a standardized and validated physician survey named the Physician Worklife Survey (PWS) (Konrad et al., Med Care, 1999). We selected three scales (7 items) relating to global job satisfaction, global career satisfaction and global specialty (family medicine) satisfaction with additional items on training and demographics. All significant variables in bivariate analyses were further examined using stepwise logistic regression. RESULTS: Out of 424 eligible family medicine physicians, 368 physicians successfully completed the questionnaire. The response rate was 86.8%. Most participants were male (52.6%), were aged between 35 and 44 years (55.5%), were FM specialists (42.4%), graduated locally (86.2%), and had postgraduate qualifications. Eighty-two percent (82%) of participants were satisfied with their training. Having autonomy and protected time for training were associated with satisfaction with FM training. Satisfaction with family medicine as a career was correlated with physicians' satisfaction with their current job. Doctors who did not enroll in training (p < 0.001) and physicians who were older (p = 0.023) were significantly less satisfied. Stepwise multivariate regression showed that doctors who subjectively believed their training as "broad and in depth' had higher career satisfaction (p < 0.001). CONCLUSION: Overall, the satisfaction level of physicians on current family medicine training in Hong Kong was high. Having autonomy and protected time for training is associated with higher training satisfaction levels. Perceiving FM training as "broad and in-depth" is associated with higher family medicine career satisfaction.

Extraction of form Factors from a Four-Dimensional Angular Analysis of B[over ¯]→D

An angular analysis of the decay B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ}, ℓ∈{e,µ}, is reported using the full e^{+}e^{-} collision data set collected by the BABAR experiment at the ϒ(4S) resonance. One B meson from the ϒ(4S)→BB[over ¯] decay is fully reconstructed in a hadronic decay mode, which constrains the kinematics and provides a determination of the neutrino momentum vector. The kinematics of the semileptonic decay is described by the dilepton mass squared, q^{2}, and three angles. The first unbinned fit to the full four-dimensional decay rate in the standard model is performed in the so-called Boyd-Grinstein-Lebed approach, which employs a generic q^{2} parametrization of the underlying form factors based on crossing symmetry, analyticity, and QCD dispersion relations for the amplitudes. A fit using the more model-dependent Caprini-Lellouch-Neubert (CLN) approach is performed as well. Our form factor shapes show deviations from previous fits based on the CLN parametrization. The latest form factors also provide an updated prediction for the branching fraction ratio R(D^{*})≡B(B[over ¯]→D^{*}τ^{-}ν[over ¯]_{τ})/B(B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ})=0.253±0.005. Finally, using the well-measured branching fraction for the B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ} decay, a value of |V_{cb}|=(38.36±0.90)×10^{-3} is obtained that is consistent with the current world average for exclusive B[over ¯]→D^{(*)}ℓ^{-}ν[over ¯]_{ℓ} decays and remains in tension with the determination from inclusive semileptonic B decays to final states with charm.

Observation of the Decay D

We report the observation of the rare charm decay D^{0}→K^{-}π^{+}e^{+}e^{-}, based on 468 fb^{-1} of e^{+}e^{-} annihilation data collected at or close to the center-of-mass energy of the ϒ(4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory. We find the branching fraction in the invariant mass range 0.675