Thrombospondins are extracellular-matrix glycoproteins implicated in the control of synaptogenesis and neurite growth. Previous microarray studies suggested that one gene of this family, ...thrombospondin 4 (THBS4), was upregulated during human brain evolution. Using independent techniques to examine thrombospondin expression patterns in adult brain samples, we report ∼6-fold and ∼2-fold greater expression of THBS4 and THBS2 messenger RNA (mRNA), respectively, in human cerebral cortex compared with chimpanzees and macaques, with corresponding differences in protein levels. In humans and chimpanzees, thrombospondin expression differences were observed in the forebrain (cortex and caudate), whereas the cerebellum and most nonbrain tissues exhibited similar levels of the 2 mRNAs. Histological examination revealed THBS4 mRNA and protein expression in numerous pyramidal and glial cells in the 3 species but humans also exhibited very prominent immunostaining of the synapse-rich cortical neuropil. In humans, additionally, THBS4 antibodies labeled β-amyloid containing plaques in Alzheimer's cases and some control cases. This is the first detailed characterization of gene-expression changes in human evolution that involve specific brain regions, including portions of cerebral cortex. Increased expression of thrombospondins in human brain evolution could result in changes in synaptic organization and plasticity, and contribute to the distinctive cognitive abilities of humans, as well as to our unique vulnerability to neurodegenerative disease.
Venous thromboembolism (VTE) remains one of the principal causes of morbidity and death in trauma patients that survive the first 24 h. Recent literature on VTE prevention focuses on choice of ...chemoprophylaxis, specifically unfractionated heparin (UFH) versus low molecular weight heparin (LMWH). This singular focus on a multifactorial process may be inadequate to fully understand the optimal approach to VTE prevention. We hypothesized that variations in care between trauma centers could be used to identify key components of VTE prevention associated with better outcomes.
A 50 question survey of VTE management for years 2014–2016 was sent to 15 trauma centers. The survey included: demographics of the trauma centers, type and timing of chemoprophylaxis, ambulation expectations, and complementary services (geriatric trauma service (GTS), mobility teams, physical and occupational therapy (PT/OT)). Each center submitted their American College of Surgeons Trauma Quality Improvement Program (TQIP) Benchmark Report for Spring 2017. TQIP data included: mortality, observed rates of deep vein thrombosis (DVT) and pulmonary embolus (PE), and time to VTE prophylaxis. The survey and TQIP reports were blinded for analysis; descriptive statistics were utilized. The top DVT & PE TQIP performers were used to identify potential aspects of better care on the survey responses. The institutions’ DVT and PE rates were then compared for these responses using Wilcoxon-Rank-Sum test.
Fifteen trauma centers (13 Level-1, 2 Level-2) completed the survey; the centers admitted 1050–7200 trauma patients per year (median 3000). The majority of centers were University-affiliated (11 of 15) with general surgery residencies (14 of 15), Acute Care Surgery or Surgical Critical Care Fellowships, (9 of 15) and critical care boarded-surgeons only on-call (9 of 15). Few have geriatric trauma services (3 of 15) or mobility teams (1 of 15). Half the trauma centers have dedicated PT/OT teams for trauma or weekend coverage. With a total of 20,878 TQIP patients analyzed, the average observed DVT and PE rates were 1.27% (range 0.1–5.2%) and 0.68% (range 0–1.6%), respectively. Weekly lower extremity surveillance duplex (2 of 15) increased DVT detection (4.15% vs 0.80%, p = 0.034) but did not decrease PE rates (1.05% vs 0.62%, p = 0.229). Great variance was seen in choice, dosing and timing of chemoprophylaxis: UFH,4 LMWH daily,1 LMWH twice-daily,5 LMWH weight-based dosing,4 and LMWH anti-Xa dosing.1 The top 3 performers for DVT and PE all used different types of chemoprophylaxis. These top performers had a prominent culture of mobility: dedicated PT/OT teams for trauma or weekends and an expectation to ambulate 3-times per day. Weekend PT/OT teams were associated with lower DVT rates (median 0.40%, range 0.10–1.10% vs 1.30%, 0.60–5.20%, p = 0.018), and ambulation 3-times per day was associated with lower PE rates (median 0.20%, range 0.00–0.20% vs 0.80%, 0.40–1.60%, p < 0.005).
Considerable variation in VTE chemoprophylaxis exists among trauma centers. “Best practices” in this area requires further investigation. An expectation of mobility and investment in mobility resources may serve to decrease VTE rates in trauma patients compared to a singular focus on type of chemoprophylaxis administered.
•Survey of trauma centers revealed great variation in VTE chemoprophylaxis.•Choice of VTE chemoprophylaxis was not associated with lower VTE rates.•TID ambulation of trauma patients was associated with lower PE rates.•Weekend mobility or PT/OT teams were associated with lower DVT rates.
Since the momentous discovery of X-rays, high-dose radiotherapy (H-XRT) has been a cornerstone for combating cancer. The high-energy electromagnetic waves induce direct damage to tumor-cells’ DNA, ...thereby halting cell growth and proliferation, and eventually leading to tumor eradication. Furthermore, recent evidence suggests that H-XRT may have immunomodulatory properties which arise from its ability to induce the release of neoantigens, which in turn prime T-cells and contribute to T-cell repertoire diversity. Throughout the years, there have been different treatment modalities introduced as complements to H-XRT that have yielded greater results than monotherapy alone. In this review, we will discuss preclinical and clinical data related to the recently introduced low-dose radiotherapy (L-XRT) modality. We will also explore the justification for combining L-XRT and H-XRT, which became known as the “RadScopal Technique”, as a novel immune adjuvant to treat cancer. In this analysis, we detail and dissect the physiological mechanisms of action of each modality and describe the synergistic amalgamation effect observed on primary and metastatic tumors. Finally, we will explore the impetus for further studies to investigate combinations of the “RadScopal Technique” with various immune-oncology drug candidates.
In humans and many other primates, the visual system plays the major role in object recognition. But objects can also be recognized through haptic exploration, which uses our sense of touch. ...Nonetheless, it has been argued that the haptic system makes use of ‘visual’ processing to construct a representation of the object. To investigate possible interactions between the visual and haptic systems, we used functional magnetic resonance imaging to measure the effects of cross-modal haptic-to-visual priming on brain activation. Subjects studied three-dimensional novel clay objects either visually or haptically before entering the scanner. During scanning, subjects viewed visually primed, haptically primed, and non-primed objects. They also haptically explored non-primed objects. Visual and haptic exploration of non-primed objects produced significant activation in several brain regions, and produced overlapping activation in the middle occipital area (MO). Viewing visually and haptically primed objects produced more activation than viewing non-primed objects in both area MO and the lateral occipital area (LO). In summary, haptic exploration of novel three-dimensional objects produced activation, not only in somatosensory cortex, but also in areas of the occipital cortex associated with visual processing. Furthermore, previous haptic experience with these objects enhanced activation in visual areas when these same objects were subsequently viewed. Taken together, these results suggest that the object-representation systems of the ventral visual pathway are exploited for haptic object perception.
The Measurements of Pollution in the Troposphere (MOPITT) satellite instrument provides the longest continuous dataset of carbon monoxide (CO) from space. We perform the first validation of MOPITT ...version 6 retrievals using total column CO measurements from ground-based remote-sensing Fourier transform infrared spectrometers (FTSs). Validation uses data recorded at 14 stations, that span a wide range of latitudes (80° N to 78° S), in the Network for the Detection of Atmospheric Composition Change (NDACC). MOPITT measurements are spatially co-located with each station, and different vertical sensitivities between instruments are accounted for by using MOPITT averaging kernels (AKs). All three MOPITT retrieval types are analyzed: thermal infrared (TIR-only), joint thermal and near infrared (TIR–NIR), and near infrared (NIR-only). Generally, MOPITT measurements overestimate CO relative to FTS measurements, but the bias is typically less than 10 %. Mean bias is 2.4 % for TIR-only, 5.1 % for TIR–NIR, and 6.5 % for NIR-only. The TIR–NIR and NIR-only products consistently produce a larger bias and lower correlation than the TIR-only. Validation performance of MOPITT for TIR-only and TIR–NIR retrievals over land or water scenes is equivalent. The four MOPITT detector element pixels are validated separately to account for their different uncertainty characteristics. Pixel 1 produces the highest standard deviation and lowest correlation for all three MOPITT products. However, for TIR-only and TIR–NIR, the error-weighted average that includes all four pixels often provides the best correlation, indicating compensating pixel biases and well-captured error characteristics. We find that MOPITT bias does not depend on latitude but rather is influenced by the proximity to rapidly changing atmospheric CO. MOPITT bias drift has been bound geographically to within ±0.5 % yr−1 or lower at almost all locations.
Bio-based platform molecules such as itaconic, fumaric, and muconic acid offer much promise in the formation of sustainable unsaturated polyester resins upon reaction with suitable diols and polyols. ...The C=C bonds present in these polyester chains allows for post-polymerization modification and such moieties are conventionally utilized in curing processes during the manufacture of coatings. The C=C modification sites can also act as points to add useful pendants which can alter the polymers final properties such as glass transition temperature, biodegradability, hardness, polarity, and strength. A commonly observed modification is the addition of secondary amines via an aza-Michael addition. Conventional procedures for the addition of amines onto itaconate polyesters require reaction times of several days as a result of undesired side reactions, in particular, the formation of the less reactive mesaconate regioisomer. The slow reversion of the mesaconate back to itaconate, followed by subsequent amine addition, is the primary reason for such extended reaction times. Herein we report our efforts toward finding a suitable catalyst for the aza-Michael addition of diethylamine onto a model substrate, dimethyl itaconate, with the aim of being able to add amine onto the itaconate units without excessive regioisomerization to the inactive mesaconate. A catalyst screen showed that iodine on acidic alumina results in an effective, heterogeneous, reusable catalyst for the investigated aza-Michael addition. Extending the study further, itaconate polyester was prepared by
(CaL-B) via enzymatic polytranesterification and subsequently modified with diethylamine using the iodine on acidic alumina catalyst, dramatically reducing the required length of reaction (>70% addition after 4 h). The approach represents a multidisciplinary example whereby biocatalytic polymerization is combined with chemocatalytic modification of the resultant polyester for the formation of useful bio-based polyesters.
Health care team members are well positioned to observe disrespectful and unsafe conduct-behaviors known to undermine team function. Based on experience in sharing patient complaints with physicians ...who subsequently achieved decreased complaints and malpractice risk, Vanderbilt University Medical Center developed and assessed the feasibility of the Co-Worker Observation Reporting System(SM) (CORS (SM)) for addressing coworkers' reported concerns.
VUMC leaders used a "Project Bundle" readiness assessment, which entailed identification and development of key people, organizational supports, and systems. Methods involved gaining leadership buy-in, recruiting and training key individuals, aligning the project with organizational values and policies, promoting reporting, monitoring reports, and employing a tiered intervention process to address reported coworker concerns.
Peer messengers shared coworker reports with the physicians and advanced practice professionals associated with at least one report 84% of the time. Since CORS inception, 3% of the medical staff was associated with a pattern of CORS reports, and 71% of recipients of pattern-related interventions were not named in any subsequent reports in a one-year follow-up period.
Systematic monitoring of documented co-worker observations about unprofessional conduct and sharing that information with involved professionals are feasible. Feasibility requires organizationwide implementation; co-workers willing and able to share respectful, nonjudgmental, timely feedback designed initially to encourage self-reflection; and leadership committed to be more directive if needed. Follow-up surveillance indicates that the majority of professionals "self-regulate" after receiving CORS data.
Macroalgae‐dominated reefs are a prominent habitat in tropical seascapes that support a diversity of fishes, including fishery target species. To what extent, then, do macroalgal habitats contribute ...to small‐scale tropical reef fisheries? To address this question we: (1) Quantified the macroalgae‐associated fish component in catches from 133 small‐scale fisheries, (2) Compared life‐history traits relevant to fishing (e.g. growth, longevity) in macroalgal and coral‐associated fishes, (3) Examined how macroalgae‐associated species can influence catch diversity, trophic level and vulnerability and (4) Explored how tropical fisheries change with the expansion of macroalgal habitats using a case study of fishery‐independent data for Seychelles. Fish that utilised macroalgal habitats comprise 24% of the catch, but very few fished species relied entirely on macroalgal or coral habitats post‐settlement. Macroalgal and coral‐associated fishes had similar life‐history traits, although vulnerability to fishing declined with increasing contribution of macroalgae association to the catch, whilst mean trophic level and diversity peaked when macroalgal‐associated fish accounted for 20%–30% of catches. The Seychelles case study revealed similar total fish biomass on macroalgal and coral reefs, although the biomass of primary target species increased as macroalgae cover expanded. Our findings reinforce that multiple habitat types are needed to support tropical fishery stability and sustainability. Whilst coral habitats have been the focus of tropical fisheries management, we show the potential for macroalgae‐associated fish to support catch size and diversity in ways that reduce vulnerability to overfishing. This is pertinent to seascapes where repeated disturbances are facilitating the replacement of coral reef with macroalgal habitats.
Patients and their families are well positioned to partner with health care organizations to help identify unsafe and dissatisfying behaviors and performance. A peer messenger process was designed by ...the Center for Professional and Patient Advocacy at Vanderbilt University Medical Center (Nashville, Tennessee) to address "high-risk" physicians identified through analysis of unsolicited patient complaints, a proxy for risk of lawsuits.
This retrospective, descriptive study used peer messenger debriefing results from data-driven interventions at 16 geographically disparate community (n = 7) and academic (n = 9) medical centers in the United States. Some 178 physicians served as peer messengers, conducting interventions from 2005, through 2009 on 373 physicians identified as high risk.
Most (97%) of the high-risk physicians received the feedback professionally, and 64% were "Responders." Responders' risk scores improved at least 15%, where Nonresponders' scores worsened (17%) or remained unchanged (19%) (p < or = .001). Responders were more often physicians practicing in medicine and surgery than emergency medicine physicians, had longer organizational tenures, and engaged in lengthier first-time intervention meetings with messengers. Years to achieve responder status correlated positively with initial communication-related complaints (r = .32, p < .001), but all complaint categories were equally likely to change over time.
Peer messengers, recognized by leaders and appropriately supported with ongoing training, high-quality data, and evidence of positive outcomes, are willing to intervene with colleagues over an extended period of time. The physician peer messenger process reduces patient complaints and is adaptable to addressing unnecessary variation in other quality/safety metrics.
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