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In this retrospective cohort study of patients presenting to a national direct-to-consumer medical practice, we found that provider geographic location is a stronger driver of antibiotic prescribing than patient location. Physicians in the Northeast and South are significantly more likely than physicians in the West to prescribe antibiotics for upper respiratory infection and bronchitis.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
OBJECTIVES/SPECIFIC AIMS: Lung cancer claims 160,000 lives in the United States every year, and lung adenocarcinoma (LADC) is the most frequent type. Early diagnosis is crucial. Computed tomography (CT) is very sensitive in identifying early-stage lung nodules, but has low specificity. Increased glucose uptake is a hallmark of cancer measurable in vivo by fluorodeoxyglucose (FDG) positron-emission tomography (PET). FDG PET is widely used for cancer staging but has low sensitivity in the diagnosis of solitary lung nodules. We have previously identified an alternative glucose transporter, SGLT2, expressed in different types of cancer but not detected by FDG PET. SGLT2 activity can be measured in vivo with the PET tracer methyl-4-fluorodeoxyglucose (Me4FDG). The objective of this study was to test the hypothesis that SGLT2 is a novel diagnostic and therapeutic target in FDG-negative, early stage LADC. METHODS/STUDY POPULATION: To study glucose transporter expression in LADC, we performed immunohistochemistry with SGLT2- and GLUT1-specific antibodies in human lung pre-malignant lesions and LADC samples. To verify the possibility of detecting SGLT2 activity in vivo, we performed microPET imaging with the SGLT-specific tracer Me4FDG in a Kras-driven, p53-null genetically engineered mouse model and in patient-derived xenografts of LADC. Finally, we performed therapeutic trials in genetically engineered and patient-derived mouse models of LADC with the FDA-approved SGLT2 inhibitor canagliflozin. RESULTS/ANTICIPATED RESULTS: We observed a switch in the modality of glucose transport during lung carcinogenesis: SGLT2 was highly expressed in pre-malignant lesions and well-differentiated LADC, whereas GLUT1 was upregulated in advanced, poorly differentiated lesions. This pattern was observed both in human samples and in murine models. This observation led us to hypothesize that early-stage LADCs are often negative on FDG PET because this imaging modality does not detect the activity of SGLT2, which is expressed in early lesions. Therefore, we performed PET imaging with the tracer Me4FDG, that measures SGLT2 activity, in our mouse model, and observed that Me4FDG accumulated in small nodules that were negative with FDG. We confirmed the functionality of SGLT2 in human LADC by Me4FDG PET in patient-derived xenografts. To investigate the role of SGLT2-mediated glucose uptake in the early stages of LADC development, we treated both genetically engineered mice and patient-derived xenografts with FDA-approved SGLT2 inhibitors, showing that SGLT2 inhibition effectively reduced LADC growth and prolonged survival in mouse models. In addition, Me4FDG uptake predicted response to SGLT2 inhibition. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results show that sodium-dependent glucose transport is a critical metabolic supply strategy in the early stages of lung adenocarcinoma development, and that Me4FDG is a novel biomarker of early LADC and of SGLT-dependent tumor growth. The discovery of SGLT2 in LADC highlighted the need for a re-interpretation of FDG-negative lung nodules, which might rely on SGLT2 for glucose uptake, and therefore may be detected by the new tracer Me4FDG. We anticipate our findings will lead to clinical studies evaluating Me4FDG as a diagnostic tracer for solitary lung nodules and early LADC, and as a biomarker for the selection of patients eligible for treatment with SGLT2 inhibitors.
In this paper, we review the status of the multifunctional experimental platform at the National Laboratory of High Power Laser and Physics (NLHPLP). The platform, including the SG-II laser facility, SG-II 9th beam, SG-II upgrade (SG-II UP) facility, and SG-II 5 PW facility, is operational and available for interested scientists studying inertial confinement fusion (ICF) and a broad range of high-energy-density physics. These facilities can provide important experimental capabilities by combining different pulse widths of nanosecond, picosecond, and femtosecond scales. In addition, the SG-II UP facility, consisting of a single petawatt system and an eight-beam nanosecond system, is introduced including several laser technologies that have been developed to ensure the performance of the facility. Recent developments of the SG-II 5 PW facility are also presented.
A direct prejudgement strategy that takes the diffraction ring as the analysis target is put forward to predict hot images induced by defects of tens of microns in the main amplifier section of high power laser systems. Analysis of hot-image formation process shows that the hot image can be precisely calculated with the extracted intensity oscillation of the diffraction ring on the front surface of the nonlinear plate. The gradient direction matching (GDM) method is adopted to detect diffraction rings. Recognition of simulated diffraction rings shows that it is feasible to directly prejudge hot images induced by those closely spaced defects and the defects that are far apart from each other. Image compression and cluster analysis are utilized to optimize the performance of the GDM method in recognizing actually collected diffraction images. Results show that hot images induced by defects of tens of microns can be directly prejudged without redundant information.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Dementia screening is a public health priority in Taiwan, where the prevalence of dementia is increasing because of an aging population. However, the reasons affect community-dwelling people to accept a referral to memory specialist clinic after dementia screening was still unclear. To investigate the feasibility, acceptability, sensitivity, and specificity of the ascertain dementia 8-item informant questionnaire (AD8) to screen for patients with cognitive impairments in Taiwan's primary healthcare system.
Researchers invited community-dwelling people whose age was above 50-year-old to attend the Memory Screening Project. AD8 was used to perform the informant interview with adult patients who were attending the Memory Screening Project in Taiwan. Individuals who scored ≥2 on the AD8 was suggested to accept referral for further cognitive performance evaluation tests, which included three validated dementia tests, i.e. the Mini-Mental Screening Examination (MMSE), the Cognitive Abilities Screening Instrument (CASI), and the Clinical Dementia Rating (CDR).
Of the 102 participants who scored ≥2 on the AD8, only 25.5% attended the referral appointment. In participants who had achieved six or more years of education, AD8 scores were not significantly different between groups and could not differentiate between the non-dementia and patients with dementia in the receiver-operator characteristics curve analysis. In contrast, in those participants who had received less than six years of education, the AD8 scores significantly differentiated between non-dementia and patients with dementia (p = 0.03).
There was a low rate of attendance at a specialist memory clinic following referral after the AD8 interview. Higher levels of education facilitated individuals to make a decision to accept the recommended referral appointment, while the AD8 showed a higher rate of differentiation between individuals who had received an education of less than six years.
Geological records have shown that the deserts east of the Helan Mountains in northern China were covered by grass during the Holocene Optimum, whereas during marine oxygen isotope stages 2 and 4 distribution of the deserts was almost the same as at present. The wide advance–retreat cycles of the deserts may have exerted an important control on grain-size changes in the loess of the Loess Plateau by altering the distance between the source and the accumulation zone of the loess. This challenges the widely accepted model that winter monsoon winds were the sole factor responsible for spatial and temporal changes in loess texture. To observe spatial changes in sedimentological characteristics of loess during the last glacial–interglacial cycle, the texture of loess was measured along a north–south transect of the Loess Plateau. This transect consists of nine loess sections, starting at Yulin in the transitional region between the Loess Plateau and the Mu Us Desert and ending at Weinan in the southernmost part of the Loess Plateau. Southward changes in sand (>63 μm) content along the transect suggest that variations in desert extent have indeed played a significant role in loess grain-size distributions, particularly in the northern part of the Loess Plateau. It is proposed that sand content (>63 μm%) of loess in the loess–desert transitional zone may be used as a proxy indicator for proximity to the desert margin.
A method to evaluate damage in optical elements with the near field of an amplified spontaneous emission (ASE) beam has been developed. Local peak intensities are generally distributed randomly in the near field of a laser beam. The partial coherence of the ASE source results in a very smooth beam profile. The coherence time of ASE is much less than the pulse width. Small-scale intensity modulations can be smoothed out rapidly within the time of a pulse width. In the experiments, ASE is generated from a multifunctional high-performance Nd:glass system, with a pulse duration of 3 ns, a spectral width (full width at half maximum, FWHM) of 1 nm and an adjustable energy range from 1 to 10 J. The damage thresholds of samples induced by ASE are two to three times higher than those induced by a laser with the same size of test spot. Furthermore, the ASE beam has great potential for the detection of defects over a large area and the conditioning of optical elements.
A high modulus, sulfonated polymer synthesized from one-to-one ratio 4,6-bis(4-hydroxyphenyl)-N, N-diphenyl-1,3,5-triazin-2-amine and 4,4′-biphenol with bis(4-fluorophenyl) sulfone (DPA-PS:BP) is exploited as an ionomer for micro-ionic actuators. A unique and attractive feature of the ionomer is that it can contain high amounts of ionic liquid (IL) as an electrolyte while maintaining a high elastic modulus (i.e 600 MPa for 150 wt% uptake), which is more than one order of magnitude higher than the state-of-the-art of ionomers with working electrolytes. Such a high modulus makes it possible for the ionomer to be fabricated into micro-actuators with high uptake of ILs and low operation voltage (< 4 V), in various free standing forms with ion milling techniques, which are attractive for MEMS applications. As an initial demonstration of a DPA-PS:BP based ionic micro-actuator, a cantilever (200 μm x 33 μm x 5 μm) is manufactured by Focused Ion Beam (FIB) and characterized. Under the voltage of 1.6 V, the bending actuator exhibits an intrinsic strain from the active ionomer of 1.1% and a corresponding blocking force of 27 μN.
It is not possible in general to constrain rock property distributions to honor the physical constraints that govern the erosion, transport, deposition, sorting, and diagenesis of sedimentary materials and the observations of properties at well locations. In many cases, however, the spatial covariance can be used to quantify the geological plausibility of a distribution of rock properties. Although there are many cases where this is not a good measure, it is important to understand what the covariance means in terms of the spatial relationship of the properties. We can begin by examining well-log traces from a well in Alaska.
Figure 5.1 shows two scaled well-logs from the same interval in the N. Kapilik 1 well (NK-1). One log is a spontaneous potential or SP log. The potentials are primarily created by diffusion of ions between the formation and the wellbore caused by differences in salinity in the fluids. Variation in the potential along the well path is due to variations in permeability as well as variations in salinity. Because clay particles have such a large effect on permeability, the SP log is often used as a shale indicator. On the other hand, the SP has relatively poor vertical resolution, and can not resolve small shales.
To get an explicit solution of a given boundary value problem is in this age of large electronic computers no longer a basic question. The problem can be coded for the machine and the numerical answer obtained. But of what value is the numerical answer if the scientist does not understand the peculiar analytical properties and idiosyncrasies of the given operator? 
The main purpose of this chapter is to develop an understanding of the spatial dependence of the sensitivity of measurements to reservoir variables, particularly porosity and permeability. The measurements provide information that improve the quality of predictions of reservoir performance. Different types of measurements are sensitive to model variables in different volumes of reservoir, and have much different complexity. Because the focus in this chapter is on qualitative understanding, for each type of data we present a plot of the sensitivity to values of reservoir properties at various locations, without equations. A straightforward, but inefficient, approach to estimating sensitivities would be to make a small change to the value of permeability or porosity in a region, then compute the change in the theoretical measurement. Vela and McKinley  used this approach to estimate sensitivity of pulse test data (a type of interference test between wells) to permeability and porosity.