Diminishing Returns: Results of Black Rail Surveys in Nebraska

The uncertain status of the Black Rail in Nebraska is problematic. Different authors have interpreted existing reports differently resulting in varying conclusions about the species’ status. The exercise of deciphering the limited details of existing reports and litigating their credibility is of little value. The Black Rail is now a threatened species and there is almost no published information on whether it occurs regularly in Nebraska. Furthermore, the species has not been searched for in any consistent form or systematic manner. Without information and understanding about the species’ occurrence, taking actions to benefit and protect this species will undoubtedly be difficult for government and non-governmental agencies or for interested individuals who want to do so. Since 2013, the Nongame Bird Program at the Nebraska Game and Parks Commission has conducted surveys focused on secretive marh birds throughout the state. Although up to eight species were targeted in these specialized surveys, a primary objective was to determine the presence/absence and/or abundance of Black Rails. Here, we report the results from our survey efforts to detect Black Rails in Nebraska

Chimeric Antigen Receptors for T-Cell Malignancies

Development of chimeric antigen receptor (CAR)-modified T cells for the treatment of T-lineage leukemia and lymphoma has encountered several unique challenges. The most widely expressed tumor antigen targets for malignant T cells are often also expressed on non-malignant T cells. Transducing T cells with CARs targeted to these shared antigens can therefore promote over-activation or fratricide of CAR T cells, reducing their therapeutic potency. If fratricide is resolved, clinical CAR T cell activity may eliminate normal T-cell subsets and cause temporary immunosuppression. In this review, we summarize the preclinical development of CAR-based therapies for T-cell malignancies and discuss strategies to minimize toxicities associated with on-target fratricide and off-tumor activity

Use of tranexamic acid in major trauma: a sex-disaggregated analysis of the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2 and CRASH-3) trials and UK trauma registry (Trauma and Audit Research Network) data

Background Women are less likely than men to receive some emergency treatments. This study examines whether the effect of tranexamic acid (TXA) on mortality in trauma patients varies by sex and whether the receipt of TXA by trauma patients varies by sex. Methods First, we conducted a sex-disaggregated analysis of data from the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH)-2 and CRASH-3 trials. We used interaction tests to determine whether the treatment effect varied by sex. Second, we examined data from the Trauma and Audit Research Network (TARN) to explore sex differences in the receipt of TXA. We used logistic regression models to estimate the odds ratio for receipt of TXA in females compared with males. Results are reported as n (%), risk ratios (RR), and odds ratios (OR) with 95% confidence intervals. Results Overall, 20 211 polytrauma patients (CRASH-2) and 12 737 patients with traumatic brain injuries (CRASH-3) were included in our analysis. TXA reduced the risk of death in females (RR=0.69 [0.52–0.91]) and in males (RR=0.80 [0.71–0.90]) with no significant heterogeneity by sex (P=0.34). We examined TARN data for 216 364 patients aged ≥16 yr with an Injury Severity Score ≥9 with 98 879 (46%) females and 117 485 (54%) males. TXA was received by 7198 (7.3% [7.1–7.4%]) of the females and 19 697 (16.8% [16.6–17.0%]) of the males (OR=0.39 [0.38–0.40]). The sex difference in the receipt of TXA increased with increasing age. Conclusions Administration of TXA to patients with bleeding trauma reduces mortality to a similar extent in women and men, but women are substantially less likely to be treated with TXA

Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma

BackgroundTotal laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.MethodsA prospectively maintained single‐institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan‐Meier survival curves and hazard ratios (HRs) were calculated.ResultsFive‐year overall survival (OS) was 49%. Five‐year disease‐free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation‐27 [ACE‐27] scale; HR 3.76; 95% confidence interval [CI] 1.56‐9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74‐4.88).ConclusionSevere comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/1/hed24918.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/2/hed24918_am.pd

East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons

Longitudinal Homogenization of the Microbiome between Both Occupants and the Built Environment in a Cohort of United States Air Force Cadets

The microbiome of the built environment has important implications for human health and wellbeing; however, bidirectional exchange of microbes between occupants and surfaces can be confounded by lifestyle, architecture, and external environmental exposures. Here, we present a longitudinal study of United States Air Force Academy cadets (n = 34), which have substantial homogeneity in lifestyle, diet, and age, all factors that influence the human microbiome. We characterized bacterial communities associated with (1) skin and gut samples from roommate pairs, (2) four built environment sample locations inside the pairs’ dormitory rooms, (3) four built environment sample locations within shared spaces in the dormitory, and (4) room-matched outdoor samples from the window ledge of their rooms

H. pylori Seropositivity before Age 40 and Subsequent Risk of Stomach Cancer: A Glimpse of the True Relationship?

Stomach carcinogenesis involves mucosal and luminal changes that favor spontaneous disappearance of Helicobacter pylori. Therefore, the association between the infection and cancer risk might typically be underestimated. As acquisition of the infection almost invariably occurs before adulthood, the serostatus at age 16–40 should best reflect the lifetime occurrence of the infection. We therefore conducted a case-control study nested within a historic cohort of about 400,000 individuals who donated sera before age 40 to either of two large Swedish Biobanks between 1968 and 2006, and whose records were linked to complete nationwide registers. For each stomach adenocarcinoma case occurring at least 5 years after serum donation 2 controls were selected matched on age, sex and year of donation and biobank. Serum immunoglobulin G antibodies against H. pylori cell-surface antigens (Hp-CSAs) were measured with an enzyme–linked immunosorbent assay and antibodies against CagA with an immunoblot assay. Conditional logistic regression models were used to estimate odds ratios (ORs) for stomach adenocarcinoma among H. pylori infected relative to uninfected. We confirmed 59 incident cases of stomach adenocarcinoma (41 non-cardia tumors) during follow-up. ORs for non-cardia stomach adenocarcinoma among subjects with Hp-CSA antibodies (regardless of CagA serostatus), antibodies against CagA (regardless of Hp-CSA serostatus), and antibodies to both, relative to those who were seronegative to both, were 17.1 (95% confidence interval [CI] 4.0–72.9), 10.9 (95% CI 3.2–36.9), and 48.5 (95% CI 5.8–407.4), respectively. H. pylori infection is a much stronger risk factor for non-cardia stomach adenocarcinoma than initially realized. However, further studies are needed to answer whether it is a necessary cause, as the possibility of misclassification of H. pylori status could not be ruled out in our study

Effect of early tranexamic acid treatment on fatigue in patients with mild traumatic brain injury: data from the CRASH-3 clinical trial

Background: Each year world-wide about 65 million people sustain a mild traumatic brain injury (mTBI). Fatigue is a common and distressing symptom after mTBI. We examine the effect of tranexamic acid (TXA) on fatigue in patients with mTBI using data from the CRASH-3 trial. Methods: The CRASH-3 trial randomised 9,202 patients with traumatic brain injury and no significant extracranial bleeding to receive TXA or placebo within 3 hours of injury. The primary outcome was death from head injury within 28 days of injury. The methods and results are presented elsewhere. Fatigue was recorded as “None”, “Moderate” or “Extreme.” This study examines the effect of TXA on extreme fatigue in the 2,632 patients with mTBI (Glasgow Coma Scale [GCS] score≥13). Our analyses were not prespecified. Results: Our study primary outcome, extreme fatigue, was reported for 10 (0.8%) of 1,328 patients receiving TXA and 19 (1.5%) of 1,288 patients receiving placebo (risk ratio [RR]=0.51, 95% confidence interval [CI] 0.24-1.09). Death within 28 days of injury was reported for 34 (2.6%) of 1,328 patients receiving TXA versus 47 (3.6%) of 1,288 patients receiving placebo (RR=0.70, 95% CI 0.45-1.08). Among patients allocated to TXA, 44 (3.3%) patients either died or reported extreme fatigue versus 66 (5.1%) patients among those allocated to placebo (RR=0.65, 95% CI 0.44-0.94). Conclusions: Early tranexamic acid treatment may reduce fatigue in mTBI patients, but these results need to be confirmed in a larger trial. Registration: ISRCTN (ISRCTN15088122, 19/07/2011), ClinicalTrials.gov (NCT01402882, 26/07/2011), EudraCT (2011-003669-14, 25/07/2011), Pan African Clinical Trial Registry (PACTR20121000441277, 30/10/2012)

Frequent Coamplification of Receptor Tyrosine Kinase and Downstream Signaling Genes in Japanese Primary Gastric Cancer and Conversion in Matched Lymph Node Metastasis

Objective: To establish the gene copy number status of receptor tyrosine kinase (RTK) and downstream signaling (DSS) genes genes in primary gastric cancer (primGC) and matched lymph node metastases (LNmet). Background: Evidence suggests that coamplification between RTKs and DSSs and conversion between primGC and LNmet are associated with resistance to targeted therapy. Methods: DNA from 237 Japanese primGC and 103 matched LNmet was analyzed using a newly developed multiplex ligation-dependent probe amplification (MLPA) probemix to investigate RTK (EGFR, HER2, FGFR2, and MET) and DSS (PIK3CA, KRAS, MYC, and CCNE1) gene copy number status. Results were compared between primGC and LNmet and related to clinicopathological data including survival. Results: A total of 150 (63%) primGC had either RTK or DSS amplification. DSS coamplification was more frequent than RTK coamplification in primGC and LNmets. Moreover, 70 (30%) GC showed a disconcordant RTK and/or DSS gene copy number status between primGC and LNmet, most common was negative conversion for DSS genes (n=40 GC). The presence of RTK amplification in primGC was related to poorer survival in univariate analysis (P=0.04). Conclusions: This is the first and most comprehensive study in gastric cancer investigating the concordance between gene copy number status of targetable RTKs and downstream signaling oncogenes in primGC and LNmets. Future studies need to establish whether the relative high frequency of RTK and DSS coamplification and/or the relative high rate of negative conversion in LNmet can potentially explain recent failures of RTK targeted therapy in gastric cancer patients