Deep CO(1–0) Observations of z = 1.62 Cluster Galaxies with Substantial Molecular Gas Reservoirs and Normal Star Formation Efficiencies

We present an extremely deep CO(1–0) observation of a confirmed z = 1.62 galaxy cluster. We detect two spectroscopically confirmed cluster members in CO(1–0) with signal-to-noise ratio $\gt 5$. Both galaxies have log(${{ \mathcal M }}_{\star }$/${{ \mathcal M }}_{\odot }$) > 11 and are gas rich, with ${{ \mathcal M }}_{\mathrm{mol}}$/(${{ \mathcal M }}_{\star }$+${{ \mathcal M }}_{\mathrm{mol}}$) ~ 0.17–0.45. One of these galaxies lies on the star formation rate (SFR)–${{ \mathcal M }}_{\star }$ sequence, while the other lies an order of magnitude below. We compare the cluster galaxies to other SFR-selected galaxies with CO measurements and find that they have CO luminosities consistent with expectations given their infrared luminosities. We also find that they have gas fractions and star formation efficiencies (SFE) comparable to what is expected from published field galaxy scaling relations. The galaxies are compact in their stellar light distribution, at the extreme end for all high-redshift star-forming galaxies. However, their SFE is consistent with other field galaxies at comparable compactness. This is similar to two other sources selected in a blind CO survey of the HDF-N. Despite living in a highly quenched protocluster core, the molecular gas properties of these two galaxies, one of which may be in the process of quenching, appear entirely consistent with field scaling relations between the molecular gas content, stellar mass, star formation rate, and redshift. We speculate that these cluster galaxies cannot have any further substantive gas accretion if they are to become members of the dominant passive population in $z\lt 1$ clusters

Knowledge, Attitudes, and Beliefs Regarding Breast and Cervical Cancer Screening among Cambodian, Laotian, Thai, and Tongan Women

Asian American Pacific Islander (AAPI) groups have low rates of breast and cervical cancer screening. This study examined knowledge, attitudes, and beliefs (KABs) regarding breast and cervical cancer on AAPI women. A cross-sectional survey of 1,808 AAPI women was included. Descriptive statistics and chi-square tests were provided and 55.3%, 68.6%, and 71.9% had received mammograms, clinical breast exam, and Pap smears, respectively. KABs on breast and cervical cancer varied between the four ethnic groups. Understanding the KABs toward cancer screening among AAPI women holds promise for identifying barriers to early detection and could aid in the creation of interventions

Beyond UVJ: Color Selection of Galaxies in the JWST Era

We present a new rest-frame color-color selection method using "synthetic $u_s-g_s$ and $g_s-i_s$'', $(ugi)_s$ colors to identify star-forming and quiescent galaxies. Our method is similar to the widely-used $U-V$ versus $V-J$ ($UVJ$) diagram. However, $UVJ$ suffers known systematics. Spectroscopic campaigns have shown that $UVJ$-selected quiescent samples at $z \gtrsim 3$ include $\sim 10-30\%$ contamination from galaxies with dust-obscured star formation and strong emission lines. Moreover, at $z>3$, $UVJ$ colors are extrapolated because the rest-frame J-band shifts beyond the coverage of the deepest bandpasses at $< 5~\mu m$ (typically $Spitzer$/IRAC 4.5 $\mu m$ or future $JWST$/NIRCam observations). We demonstrate that $(ugi)_s$ offers improvements to $UVJ$ at $z>3$, and can be applied to galaxies in the $JWST$ era. We apply $(ugi)_s$ selection to galaxies at $0.5<z<6$ from the (observed) 3D-HST and UltraVISTA catalogs, and to the (simulated) JAGUAR catalogs. We show that extrapolation can affect $(V-J)_0$ color by up to 1 magnitude, but changes $(u_s-i_s)_0$ color by $\leq$ 0.2 mag, even at $z\simeq 6$. While $(ugi)_s$-selected quiescent samples are comparable to $UVJ$ in completeness (both achieve $\sim$85-90% at $z=3-3.5$), $(ugi)_s$ reduces contamination in quiescent samples by nearly a factor of two, from $\simeq$35% to $\simeq$17% at $z=3$, and from $\simeq$60% to $\simeq$33% at $z=6$. This leads to improvements in the true-to-false-positive ratio (TP/FP), where we find TP/FP $\gtrsim$ 2.2 for $(ugi)_s$ at $z \simeq 3.5 - 6$, compared to TP/FP $<$ 1 for $UVJ$-selected samples. This indicates that contaminants will outnumber true quiescent galaxies in $UVJ$ at these redshifts, while $(ugi)_s$ will provide higher-fidelity samples.Comment: Submitted to Ap

The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

The FENIKS Survey: Spectroscopic Confirmation of Massive Quiescent Galaxies at z ~ 3-5

The measured ages of massive, quiescent galaxies at $z\sim 3-4$ imply that massive galaxies quench as early as $z\sim 6$. While the number of spectroscopic confirmations of quiescent galaxies at $z < 3$ has increased over the years, there are only a handful at $z > 3.5$. We report spectroscopic redshifts of one secure ($z=3.757$) and two tentative ($z = 3.336$, $z=4.673$) massive ($\log(M_\ast/M_\odot) > 10.3$) quiescent galaxies with 11 hours of Keck/MOSFIRE $K$-band observations. Our candidates were selected from the FENIKS survey, which uses deep Gemini/Flamingos-2 $K_b$ $K_r$ imaging optimized for increased sensitivity to the characteristic red colors of galaxies at $z > 3$ with strong Balmer/4000 \AA\ breaks. The rest-frame $UVJ$ and $(ugi)_s$ colors of 3/4 quiescent candidates are consistent with $1-2$ Gyr old stellar populations. This places these galaxies as the oldest objects at these redshifts, and challenges the notion that quiescent galaxies at $z > 3$ are all recently-quenched, "post-starburst'' galaxies. Our spectroscopy shows that the other quiescent-galaxy candidate is a broad-line AGN ($z = 3.594$) with strong, redshifted $H\beta$+[O III] emission with a velocity offset $>1000$ km/s, indicative of a powerful outflow. The star-formation history of our highest redshift candidate suggests that its progenitor was already in place by $z \sim 7-11$, reaching $\sim$ 10$^{11} M_{\odot}$ by $z \simeq 10$. These observations reveal the limit of what is possible with deep near-infrared photometry and targeted spectroscopy from the ground and demonstrate that secure spectroscopic confirmation of quiescent galaxies at $z > 4$ is only feasible with JWST.Comment: 20 pages, 11 figures, submitted to Ap

Prophylactic and Therapeutic Efficacy of Avian Antibodies against Influenza Virus H5N1 and H1N1 in Mice

Background: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs) have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY) found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV) strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We reasoned that IgY from consumable eggs available in supermarkets in Vietnam could provide protection against infections with HPAIV H5N1. Methods and Findings: We found that H5N1-specific IgY that are prepared from eggs available in supermarkets in Vietnam by a rapid and simple water dilution method cross-protect against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection, the IgY prevent the infection or significantly reduce viral replication resulting in complete recovery from the disease, respectively. We further generated H1N1 virus-specific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for the current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection. Conclusions: The findings suggest that readily available H5N1-specific IgY offer an enormous source of valuable biological material to combat a potential H5N1 pandemic. In addition, our study provides a proof-of-concept for the approach using virus-specific IgY as affordable, safe, and effective alternative for the control of influenza outbreaks, including the current H1N1 pandemic

The usefulness of the electronic patient visit assessment (ePVA) as a clinical support tool for real-time interventions in head and neck cancer

Background: Patients with head and neck cancer (HNC) experience painful, debilitating symptoms and functional limitations that can interrupt cancer treatment, and decrease their health-related quality of life (HRQoL). The Electronic Patient Visit Assessment (ePVA) for head and neck is a web-based mHealth patient-reported measure that asks questions about 21 categories of symptoms and functional limitations common to HNC. This article presents the development and usefulness of the ePVA as a clinical support tool for real-time interventions for patient-reported symptoms and functional limitations in HNC. Methods: Between January 2018 and August 2019, 75 participants were enrolled in a clinical usefulness study of the ePVA. Upon signing informed consent, participants completed the ePVA and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) general (C30) questionnaire v3.0 (scores range from 0 to 100 with 100 representing best HRQoL). Clinical usefulness of the ePVA was defined as demonstration of reliability, convergent validity with HRQoL, and acceptability of the ePVA (i.e., >70% of eligible participants complete the ePVA at two or more visits and >70% of ePVA reports are read by providers). Formal focus group discussions with the interdisciplinary teamthat cared for patients with HNC guided the development of the ePVA as a clinical support tool. Qualitative and quantitative methods were used throughout the study. Descriptive statistics consisting of means and frequencies, Pearson correlation coefficient, and Student’s t-tests were calculated using SAS 9.4 and STATA. Results: The participants were primarily male (71%), White (76%), diagnosed with oropharyngeal or oralcavity cancers (53%), and undergoing treatment for HNC (69%). Data analyses supported the reliability (alpha =0.85), convergent validity with HRQoL scores, and acceptability of the ePVA. Participants with the highest number of symptoms and functional limitations reported significantly worse HRQoL (sumof symptoms: r=–0.50, P<0.0001; sum of function limitations: r=–0.56, P<0.0001). Ninety-two percent of participants (59 of 64) who had follow-up visits within the 6-month study period completed the ePVA at twoor more visits and providers read 89% (169 of 189) of automated ePVA reports. The use of the ePVA as aclinical support tool for real-time interventions for symptoms and functional limitations reported by patients is described in a clinical exemplar. Conclusions: This research indicates that the ePVA may be a useful mHealth tool as a clinical support tool for real-time interventions for patient-reported symptoms and functional limitations in HNC. The study findings support future translational research to enhance the usefulness of the ePVA in real world settings for early interventions that decrease symptom burden and improve the QoL of patients with HNC

Quantitative Modeling of GRK-Mediated β2AR Regulation

We developed a unified model of the GRK-mediated β2 adrenergic receptor (β2AR) regulation that simultaneously accounts for six different biochemical measurements of the system obtained over a wide range of agonist concentrations. Using a single deterministic model we accounted for (1) GRK phosphorylation in response to various full and partial agonists; (2) dephosphorylation of the GRK site on the β2AR; (3) β2AR internalization; (4) recycling of the β2AR post isoproterenol treatment; (5) β2AR desensitization; and (6) β2AR resensitization. Simulations of our model show that plasma membrane dephosphorylation and recycling of the phosphorylated receptor are necessary to adequately account for the measured dephosphorylation kinetics. We further used the model to predict the consequences of (1) modifying rates such as GRK phosphorylation of the receptor, arrestin binding and dissociation from the receptor, and receptor dephosphorylation that should reflect effects of knockdowns and overexpressions of these components; and (2) varying concentration and frequency of agonist stimulation “seen” by the β2AR to better mimic hormonal, neurophysiological and pharmacological stimulations of the β2AR. Exploring the consequences of rapid pulsatile agonist stimulation, we found that although resensitization was rapid, the β2AR system retained the memory of the previous stimuli and desensitized faster and much more strongly in response to subsequent stimuli. The latent memory that we predict is due to slower membrane dephosphorylation, which allows for progressive accumulation of phosphorylated receptor on the surface. This primes the receptor for faster arrestin binding on subsequent agonist activation leading to a greater extent of desensitization. In summary, the model is unique in accounting for the behavior of the β2AR system across multiple types of biochemical measurements using a single set of experimentally constrained parameters. It also provides insight into how the signaling machinery can retain memory of prior stimulation long after near complete resensitization has been achieved

Importance of pre-analytical steps for transcriptome and RT-qPCR analyses in the context of the phase II randomised multicentre trial REMAGUS02 of neoadjuvant chemotherapy in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Identification of predictive markers of response to treatment is a major objective in breast cancer. A major problem in clinical sampling is the variability of RNA templates, requiring accurate management of tumour material and subsequent analyses for future translation in clinical practice. Our aim was to establish the feasibility and reliability of high throughput RNA analysis in a prospective trial.</p> <p>Methods</p> <p>This study was conducted on RNA from initial biopsies, in a prospective trial of neoadjuvant chemotherapy in 327 patients with inoperable breast cancer. Four independent centres included patients and samples. Human U133 GeneChips plus 2.0 arrays for transcriptome analysis and quantitative RT-qPCR of 45 target genes and 6 reference genes were analysed on total RNA.</p> <p>Results</p> <p>Thirty seven samples were excluded because <it>i) </it>they contained less than 30% malignant cells, or <it>ii) </it>they provided RNA Integrity Number (RIN) of poor quality. Among the 290 remaining cases, taking into account strict quality control criteria initially defined to ensure good quality of sampling, 78% and 82% samples were eligible for transcriptome and RT-qPCR analyses, respectively. For RT-qPCR, efficiency was corrected by using standard curves for each gene and each plate. It was greater than 90% for all genes. Clustering analysis highlighted relevant breast cancer phenotypes for both techniques (ER+, PR+, HER2+, triple negative). Interestingly, clustering on trancriptome data also demonstrated a "centre effect", probably due to the sampling or extraction methods used in on of the centres. Conversely, the calibration of RT-qPCR analysis led to the centre effect withdrawing, allowing multicentre analysis of gene transcripts with high accuracy.</p> <p>Conclusions</p> <p>Our data showed that strict quality criteria for RNA integrity assessment and well calibrated and standardized RT-qPCR allows multicentre analysis of genes transcripts with high accuracy in the clinical context. More stringent criteria are needed for transcriptome analysis for clinical applications.</p