Symptom Burden, Survival and Palliative Care in Advanced Soft Tissue Sarcoma

Introduction. The symptom burden and role of palliative care (PC) in patients with advanced soft tissue sarcoma (STS) are not well defined. Methods. This study retrospectively reviewed both symptoms and PC involvement in patients known to an STS referral centre who died in one calendar year. Results. 81 patients met inclusion criteria of which 27% had locally advanced disease and 73% metastases at initial referral. The median number of symptoms was slowly progressive ranging from 2 (range 0–5) before first-line chemotherapy (n = 50) to 3 (range 1–6) at the time of best supportive care (BSC) decision (n = 48). Pain and dyspnoea were the commonest symptoms. Median overall survival from BSC decision was 3.4 weeks. 88% had PC involvement (either hospital, community, or both) with median time from first PC referral to death of 16 (range 0–110) weeks. Conclusions. Patients with metastatic STS have a significant symptom burden which justifies early PC referral. Pain, including neuropathic pain, is a significant problem. Dyspnoea is common, progressive and appears to be undertreated. Time from BSC decision to death is short, and prospective studies are required to determine whether this is due to overtreatment or very rapid terminal disease progression

Early development of rostrum saw-teeth in a fossil ray tests classical theories of the evolution of vertebrate dentitions

In classical theory, teeth of vertebrate dentitions evolved from co-option of external skin denticles into the oral cavity. This hypothesis predicts that ordered tooth arrangement and regulated replacement in the oral dentition were also derived from skin denticles. The fossil batoid ray Schizorhiza stromeri (Chondrichthyes; Cretaceous) provides a test of this theory. Schizorhiza preserves an extended cartilaginous rostrum with closely spaced, alternating saw-teeth, different from sawfish and sawsharks today. Multiple replacement teeth reveal unique new data from micro-CT scanning, showing how the 'cone-in-cone' series of ordered saw-teeth sets arrange themselves developmentally, to become enclosed by the roots of pre-existing saw-teeth. At the rostrum tip, newly developing saw-teeth are present, as mineralized crown tips within a vascular, cartilaginous furrow; these reorient via two 90° rotations then relocate laterally between previously formed roots. Saw-tooth replacement slows mid-rostrum where fewer saw-teeth are regenerated. These exceptional developmental data reveal regulated order for serial self-renewal, maintaining the saw edge with ever-increasing saw-tooth size. This mimics tooth replacement in chondrichthyans, but differs in the crown reorientation and their enclosure directly between roots of predecessor saw-teeth. Schizorhiza saw-tooth development is decoupled from the jaw teeth and their replacement, dependent on a dental lamina. This highly specialized rostral saw, derived from diversification of skin denticles, is distinct from the dentition and demonstrates the potential developmental plasticity of skin denticles

Enhanced He-alpha emission from "smoked" Ti targets irradiated with 400nm, 45 fs laser pulses

We present a study of He-like 1s(2)-1s2p line emission from solid and low-density Ti targets under similar or equal to 45 fs laser pulse irradiation with a frequency doubled Ti: Sapphire laser. By varying the beam spot, the intensity on target was varied from 10(15) W/cm(2) to 10(19) W/cm(2). At best focus, low density "smoked" Ti targets yield similar to 20 times more He-alpha than the foil targets when irradiated at an angle of 45 degrees with s-polarized pulses. The duration of He-alpha emission from smoked targets, measured with a fast streak camera, was similar to that from Ti foils

Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19.

Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens

Vortical and Wave Modes in 3D Rotating Stratified Flows: Random Large Scale Forcing

Utilizing an eigenfunction decomposition, we study the growth and spectra of energy in the vortical and wave modes of a 3D rotating stratified fluid as a function of $\epsilon = f/N$. Working in regimes characterized by moderate Burger numbers, i.e. $Bu = 1/\epsilon^2 < 1$ or $Bu \ge 1$, our results indicate profound change in the character of vortical and wave mode interactions with respect to $Bu = 1$. As with the reference state of $\epsilon=1$, for $\epsilon < 1$ the wave mode energy saturates quite quickly and the ensuing forward cascade continues to act as an efficient means of dissipating ageostrophic energy. Further, these saturated spectra steepen as $\epsilon$ decreases: we see a shift from $k^{-1}$ to $k^{-5/3}$ scaling for $k_f < k < k_d$ (where $k_f$ and $k_d$ are the forcing and dissipation scales, respectively). On the other hand, when $\epsilon > 1$ the wave mode energy never saturates and comes to dominate the total energy in the system. In fact, in a sense the wave modes behave in an asymmetric manner about $\epsilon = 1$. With regard to the vortical modes, for $\epsilon \le 1$, the signatures of 3D quasigeostrophy are clearly evident. Specifically, we see a $k^{-3}$ scaling for $k_f < k < k_d$ and, in accord with an inverse transfer of energy, the vortical mode energy never saturates but rather increases for all $k < k_f$. In contrast, for $\epsilon > 1$ and increasing, the vortical modes contain a progressively smaller fraction of the total energy indicating that the 3D quasigeostrophic subsystem plays an energetically smaller role in the overall dynamics.Comment: 18 pages, 6 figs. (abbreviated abstract

Hybrid Theory: Creation of a Faculty Position That Allows Half-Time Hospice Employment Alongside Academic Palliative Care

BACKGROUND: The specialty of hospice and palliative medicine struggles to merge the fast-paced technological consultative work of acute hospital palliative care with slower paced and home-based hospice. Each has equal if different merits. Here, we describe creation of a position that allowed half-time hospice employment, alongside academic hospital-based palliative care. METHODS: Johns Hopkins Medicine and Gilchrist, Inc., a large nonprofit hospice, partnered to form a joint position with time spent equally between the two locations. RESULTS: Created as a university position with leasing to the hospice, specific attention has been paid to mentoring at both sites to allow professional advancement. Both organizations have benefited in terms of recruitment, and more physicians have chosen this dual pathway suggesting that it is working well. DISCUSSION: Hybrid positions are possible and may be desired by those who wish to practice both palliative medicine and hospice. Creation of one successful position helped recruit a second and a third candidate a year later. The original recipient has been promoted within Gilchrist to direct the inpatient unit. Such positions require careful mentoring and coordination to allow success at both sites and this can be done with foresight

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

Mexico City and the biogeochemistry of global urbanization

Mexico City is far advanced in its urban evolution, and cities in currently developing nations may soon follow a similar course. This paper investigates the strengths and weaknesses of infrastructures for the emerging megacities. The major driving force for infrastructure change in Mexico City is concern over air quality. Air chemistry data from recent field campaigns have been used to calculate fluxes in the atmosphere of the Valley of Mexico, for compounds that are important to biogeochemistry including methane (CH4), carbon monoxide (CO), nonmethane hydrocarbons (NMHCs), ammonia (NH3), sulfur dioxide (SO2), nitrogen oxides (NOx and NOy), soot, and dust. Leakage of liquified petroleum gas approached 10% during sampling periods, and automotive pollutant sources in Mexico City were found to match those in developed cities, despite a lower vehicle-to-person ratio of 0.1. Ammonia is released primarily from residential areas, at levels sufficient to titrate pollutant acids into particles across the entire basin. Enhancements of reduced nitrogen and hydrocarbons in the vapor phase skew the distribution of NOy species towards lower average deposition velocities. Partly as a result, downwind nutrient deposition occurs on a similar scale as nitrogen fixation across Central America, and augments marine nitrate upwelling. Dust suspension from unpaved roads and from the bed of Lake Texcoco was found to be comparable to that occurring on the periphery of the Sahara, Arabian, and Gobi deserts. In addition, sodium chloride (NaCl) in the dust may support heterogeneous chlorine oxide (ClOx) chemistry. The insights from our Mexico City analysis have been tentatively applied to the upcoming urbanization of Asia

Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China

A key observation about the human immune response to repeated exposure to influenza A is that the first strain infecting an individual apparently produces the strongest adaptive immune response. Although antibody titers measure that response, the interpretation of titers to multiple strains - from the same sera - in terms of infection history is clouded by age effects, cross reactivity and immune waning. From July to September 2009, we collected serum samples from 151 residents of Guangdong Province, China, 7 to 81 years of age. Neutralization tests were performed against strains representing six antigenic clusters of H3N2 influenza circulating between 1968 and 2008, and three recent locally circulating strains. Patterns of neutralization titers were compared based on age at time of testing and age at time of the first isolation of each virus. Neutralization titers were highest for H3N2 strains that circulated in an individual's first decade of life (peaking at 7 years). Further, across strains and ages at testing, statistical models strongly supported a pattern of titers declining smoothly with age at the time a strain was first isolated. Those born 10 or more years after a strain emerged generally had undetectable neutralization titers to that strain (<1:10). Among those over 60 at time of testing, titers tended to increase with age. The observed pattern in H3N2 neutralization titers can be characterized as one of antigenic seniority: repeated exposure and the immune response combine to produce antibody titers that are higher to more 'senior' strains encountered earlier in life. © 2012 Lessler et al.published_or_final_versio