Assessing Laws and Legal Authorities for Obesity Prevention and Control

This is the first paper in a two part series on the laws and legal authorities for obesity prevention and control, which resulted from the National Summit on Legal Preparedness for Obesity Prevention and Control in 2008. In this paper, the authors apply the “laws and legal authorities” component of the Centers for Disease Control and Prevention (CDC) legal framework on public health legal preparedness to demonstrate the essential role that law can play in the fight against obesity. Their analysis identified numerous laws and policies in the three vital domains of healthy lifestyles, healthy places, and healthy societies. For example, in terms of healthy lifestyles, governments can impact nutrition through: food subsidies, taxation, and bans; food marketing strategies; and nutritional labeling and education. With regard to healthy places, state and local governments can apply zoning laws and policy decisions to change the environment to encourage healthy eating and physical activity. Governments can promote healthy societies through laws and legal authorities that affect the ability to address obesity from a social perspective (such as antidiscrimination law, health care insurance and benefit design, school and day care for children, and surveillance). This paper describes instances of how current laws and legal authorities affect the public health goal of preventing obesity in both positive and negative ways. It also highlights the progressive use of laws at every level of government (i.e., federal, state, and local) and the interaction of these laws as they relate to obesity prevention and control. In addition, general gaps in the use of law for obesity prevention and control are identified for attention and action. (These gaps serve as the basis for the companion paper, which delineates options for policymakers, practitioners, and other key stakeholders in the improvement of laws and legal authorities for obesity prevention and control.

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

PURPOSE: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. RESULTS: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations. CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.Core funding for this project was provided by the National Institutes of Health (R01-CA172404, PI: S.J. Ramus; and R01-CA168758, PIs: J.A. Doherty and M.A.Rossing), the Canadian Institutes for Health Research (Proof-of-Principle I program, PIs: D.G.Huntsman and M.S. Anglesio), the United States Department of Defense Ovarian Cancer Research Program (OC110433, PI: D.D. Bowtell). A. Talhouk is funded through a Michael Smith Foundation for Health Research Scholar Award. M.S. Anglesio is funded through a Michael Smith Foundation for Health Research Scholar Award and the Janet D. Cottrelle Foundation Scholars program managed by the BC Cancer Foundation. J. George was partially supported by the NIH/National Cancer Institute award number P30CA034196. C. Wang was a Career Enhancement Awardee of the Mayo Clinic SPORE in Ovarian Cancer (P50 CA136393). D.G. Huntsman receives support from the Dr. Chew Wei Memorial Professorship in Gynecologic Oncology, and the Canada Research Chairs program (Research Chair in Molecular and Genomic Pathology). M. Widschwendter receives funding from the European Union’s Horizon 2020 European Research Council Programme, H2020 BRCA-ERC under Grant Agreement No. 742432 as well as the charity, The Eve Appeal (https://eveappeal.org.uk/), and support of the National Institute for Health Research (NIHR) and the University College London Hospitals (UCLH) Biomedical Research Centre. G.E. Konecny is supported by the Miriam and Sheldon Adelson Medical Research Foundation. B.Y. Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. H.R. Harris is 20 supported by the NIH/National Cancer Institute award number K22 CA193860. OVCARE (including the VAN study) receives support through the BC Cancer Foundation and The VGH+UBC Hospital Foundation (authors AT, BG, DGH, and MSA). The AOV study is supported by the Canadian Institutes of Health Research (MOP86727). The Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group, was funded by the National Health and Medical Research Council Enabling Grants ID 310670 & ID 628903 and the Cancer Institute NSW Grants ID 12/RIG/1-17 & 15/RIG/1-16. The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Foundation of Western Australia (Multi-State Applications 191, 211 and 182) and the National Health and Medical Research Council of Australia (NHMRC; ID199600; ID400413 and ID400281). BriTROC-1 was funded by Ovarian Cancer Action (to IAM and JDB, grant number 006) and supported by Cancer Research UK (grant numbers A15973, A15601, A18072, A17197, A19274 and A19694) and the National Institute for Health Research Cambridge and Imperial Biomedical Research Centres. Samples from the Mayo Clinic were collected and provided with support of P50 CA136393 (E.L.G., G.L.K, S.H.K, M.E.S.)

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

DETECTION OF THE NEAR-INFRARED SPECTRUM OF CH2+CH_{2}{^{+}}

$^{a}$M. R\""{o}sslein, C.M. Gabrys, M.-F. Jagod, and T. Oka, J. Mol. Spectrosc. 153, 738 (1992) $^{b}$P. Jensen, M. Brumm, W.P. Kraemer, and P.R. Bunker, J. Mol. Spectrosc. 172, 194 (1995) $^{c}$S. Willitsch and F. Merkt, J. Chem. Phys. 118, 2235 (2003) $^{d}$P.R. Bunker, M.C. Chan, W.P. Kraemer, and P. Jensen, Chem. Phys. Lett. 341, 358 (2001)Author Institution: Department of Chemistry, University of Chicago; Department of Astronomy \& Astrophysics, and the Enrico Fermi Institute, University of ChicagoThe molecular ion $CH_{2}{^{+}}$ is of special interest because of its quasilinearity (resulting from a small barrier to linearity, $1089 cm^{-1}$) and the strong interaction of its ground and first excited states due to the Renner-Teller effect. At linearity the ground state is a doubly degenerate ${^{2}}\Pi_{u}$ state that splits into $\widetilde{X}^{2}A_{1}$ and $\widetilde{A}^{2}B_{1}$ states as the molecule bends. Although in the ground state the molecule is a near-prolate asymmetric rotor $(\angle HCH=140^{\circ})$, the excited state equilibrium geometry is linear. Both the initial detection of the infrared spectrum of the $\nu_{3}$ $band^{a,b}$ and a more recent PFI-ZEKE $study^{c}$ confirm the bent nature of $CH_{2}{^{+}}$ in the ground state. This work presents the first experimental spectroscopic characterization of the $\widetilde{A}^{2}B_{1}$ state. Using a Ti:sapphire laser, we have observed four new absorption bands in the near-infrared region $(11,000-13,000 cm^{-1})$. The comparison between spectra recorded in $He/CH_{4}$ and $He/CH_{4}/H_{2}$ liquid-nitrogen cooled positive column discharges was used to identify these transitions, the strongest of which had a signal-to-noise ratio of ${\sim} 100$. A least-squares fit of 57 transitions from the $\widetilde{A}(0,3,0)^{1} \leftarrow \widetilde{X}(0,0,0)^{0}$ band has given preliminary values for the excited state molecular constants $B=7.140(22)$ and $D_{N}=-0.00034(16)$. The fit of 46 lines from the $\widetilde{A}(0,4,0)^{0} \leftarrow \widetilde{X}(0,0,0)^{1}$ band resulted in the following excited state constants: $B=6.796(56)$ and $D_{N}=-0.00170(42)$. Recent ab initio $predictions^{d}$ of the rovibronic spectra of $CH_{2}{^{+}}$ show good agreement with the observed spectrum ($\Delta \nu_{o-c}=-53 cm^{-1}$ for the $\widetilde{A}(0,3,0)^{1}\leftarrow \widetilde{X}(0,0,0)^{0}$ band and $\Delta \nu_{o-c}=- 18 cm^{-1}$ for the $\widetilde{A}(0,4,0)^{0}\leftarrow \widetilde{X}(0,0,0)^{1}$ band). Assignment of the $\widetilde{A}(0,3,0)^{2}\leftarrow \widetilde{X}(0,0,0)^{1}$ and $\widetilde{A}(0,3,0)^{3}\leftarrow \widetilde{X}(0,0,0)^{2}$ bands is underway

RADIATIVE LIFETIMES OF NiH AND CoH

$^{a}$ S. A. Kadavthu, R. Scullman, R. W. Field, J. A. Gray, and M. Li, J. Mol. Spectrosc, 147, 448-470 (1991). $^{b}$ T.D. Varberg, E. J. Hill, and R. W. Field, J. Mol. Spectrosc, 138, 630-637 (1989).Author Institution: Department of Chemistry, Ohio Northern UniversityRadiative lifetimes have been measured for several excited electronic states of NiH and radicals, which are produced by laser ablation in a pulsed free-jet expansion of argon containing pentane vapor. $Known^{ab}$ transitions in the 15,500 to $18,200 cm^{-1}$ region were excited using a pulsed dye laser, and lifetimes varying from approx. 0.5 to $5 \mu s$ were determined by temporally resolving the fluorescence intensity. The lifetimes of some states depend on rotational level and/or parity, The electronic structure of transition-metal radicals is generally difficult to model or theoretically predict, especially for optically excited states. While observations such as magnetic moments, A-doubling, and spin-orbit intervals can aid in understanding perturbations, radiative lifetimes may be a better diagnostic for assigning the spin multiplicity of the excited states when the low-lying states have will-defined spin

HIGH-RESOLUTION NEAR-INFRARED SPECTROSCOPY OF He/N2_2/H2_2 POSITIVE-COLUMN PLASMAS

{M. Okumura, B. D. Rehfuss, B. M. Dinelli, M. G. Bawendi, and T. Oka, J. Chem. Phys. \textbf{90{Y. Kabbadj, T. R. Huet, D. Uy, and T. Oka, J. Mol. Spectrosc. \textbf{175{G. Osmann, P. R. Bunker, P. Jensen, and W. P. Kraemer, J. Mol. Spectrosc. \textbf{186Author Institution: Department of Chemistry, Department of Astronomy $\&$ Astrophysics,; and the Enrico Fermi Institute, University of Chicago, Chicago, IL 60637Like its isoelectronic cousins BH$_2^-$ and CH$_2$, the amidogen cation NH$_2^+$ has a quasilinear ground state $\widetilde{X}$$^3$B$_1$ with a low barrier to linearity (155 cm$^{-1}$) and metastable excited electronic states $\widetilde{a}$$^1$A$_1$ and $\widetilde{b}$$^1$B$_1$ that become degenerate ($^1\Delta$) at linearity. In addition to its theoretical interest (due to the quasilinearity and the Renner effect), NH$_2^+$ is one of the most fundamental molecular ions that exist abundantly in laboratory plasmas containing hydrogen and nitrogen. Despite this, only two high-resolution experimental detections of NH$_2^+$ have been reported (the observation of the antisymmetric N-H stretch}, 5918 (1989).} at 3360 cm$^{-1}$, and four hot bands}, 277 (1996).} from 2900-3500 cm$^{-1}$). \vspace{1em} In an attempt to observe the predicted near-infrared electronic absorption spectrum of NH$_2^+$,}, 319 (1997).} we have recently obtained new spectra of positive ions in a liquid-nitrogen-cooled positive column He/N$_2$/H$_2$ plasma. The spectra were recorded using a high-resolution, high-sensitivity spectrometer based on a Ti:sapphire laser (11,000-13,000 cm$^{-1}$) and incorporating velocity modulation, phase modulation with heterodyne detection, noise subtraction, and optical multi-passing. The observation and assignment of the spectra is complicated by the presence of thousands of lines from the $A^2\Pi_u - X^2\Sigma_g^+$ system of N$_2^+$. We will report the results of our analysis of the new spectra

Laser-induced air shock from energetic materials (LASEM): a novel microscale technique for characterizing energy release at high heating rates

In this review we detail the expansion of laser-induced shock waves into the air following nanosecond-pulsed laser ablation of energetic materials for comparison of the microsecond-timescale energy release among different samples; subsequent self-sustained combustion reactions provide information about the millisecond-timescale energy release. This technique is called laser-induced air shock from energetic materials (LASEM). A detailed description of the processes involved in LASEM is presented, along with the experimental conditions for successfully differentiating similar energetic materials. The influence of material properties and sample preparation, laser properties, high-speed imaging parameters, and data fitting methodology on the characteristic laser-induced shock velocities is reviewed with relevant examples. Related work by other groups is also discussed, demonstrating the increasing usage of laser-induced plasmas and their subsequent effects for energetic material characterization on a laboratory scale. We provide examples of recent capability upgrades. Finally, we enumerate the open questions relating to LASEM experimental results and their relationship to detonation chemistry.</p

THE NEAR-INFRARED SPECTRUM OF CH2+_2^+

{J. L. Gottfried and T. Oka, \textit{J. Chem. Phys.Author Institution: Department of Chemistry, Department of Astronomy \& Astrophysics,; and the Enrico Fermi Institute, The University of Chicago, Chicago; IL, 60637, USAThe molecular ion CH$_2^+$ is of special theoretical interest because it is both quasi-linear and exhibits a strong Renner-Teller interaction between its ground and first-excited electronic states. At linearity, the ground state is a $^{2}\Pi_{u}$ state that splits into $\tilde{X}^{2}A_{1}$ and $\tilde{A}^{2}B_{2}$ states as the molecule bends. The $\tilde{A}$ state is linear, while the $\tilde{X}$ is quasi-linear with a barrier to linearity of only 1089 \wn. Thus, only the ground vibrational state is bound by the barrier to linearity. \vspace{2ex} The spectrum of CH$_2^+$ in the region 11,000--13,000 \wn\ has been recorded with our Ti:sapphire laser spectrometer. This spectrometer couples velocity modulation with heterodyne detection for near shot-noise-limited sensitivity. Since our initial letter on this spectrum,} \textbf{121}, 11527 (2004).} we have selectively rescanned portions of this spectrum with improved signal-to-noise. As a result, we have been able to assign the $\tilde{A}(0,3,0)^3 \leftarrow \tilde{X}(0,0,0)^2$ band and detect the $\tilde{X}(0,9,0)^2 \leftarrow \tilde{X}(0,0,0)^1$ band, whose assignment is in progress. A more detailed analysis of the entire spectrum, including spin splitting, is underway