Please note, due to essential maintenance online transactions will not be possible between 02:30 and 04:00 BST, on Tuesday 17th September 2019 (22:30-00:00 EDT, 17 Sep, 2019). We apologise for any inconvenience.
To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The original research by the Teotihuacan Mapping Project (TMP) identified a large number of obsidian workshops within Teotihuacan based on surface concentrations of production debris. Clark (1986b) questioned the validity of these identifications and called for subsurface excavation to confirm the presence of in situ workshop locales. This article summarizes the results from the excavation of one of the obsidian workshops identified in the Tlajinga district of Teotihuacan at Compound 17:S3E1 (Compound 17). We describe the excavations, discuss the lithic technology, and examine the subsurface contexts in terms of what they tell us about in situ obsidian craft activity. Excavations confirm that Compound 17 was a locus of large-scale obsidian craft production during the Classic period. While only a single test case, these results suggest that surface remains at Teotihuacan can be a useful guide in identifying craft production areas when they are confirmed through subsurface testing.
Hemophilia gene therapy trials demonstrate a “cure” could be achievable, thereby changing disease management. CoreHEM aims to develop multi-stakeholder consensus around a clearly defined, core outcome set (COS) - a minimum set of outcomes that should be measured and reported in all clinical trials of a specific condition - that will demonstrate and allow differentiation of the effectiveness and value of gene therapy relative to the current standard of care. Health technology assessment (HTA) frequently suffers from a lack of relevant, consistently reported outcomes. When uniformly implemented, COS increase the predictability and consistency of appraisals, coverage, and reimbursement decisions by payers and HTA agencies.
A COS was developed using a modified Delphi process, including online surveys and an in-person consensus meeting. A literature review and key informant interviews were used to create an initial list of outcomes for voting. Participants (patients, including representatives from the National Hemophilia Foundation and the World Federation of Hemophilia, healthcare providers, payers, HTA agencies, regulators and industry representatives) condensed and prioritized the list by rating each outcome on a scale of 1 (not important to include) to 9 (essential). Participants could also suggest outcomes for voting. Outcomes were eliminated from consideration if <70 percent rated the outcome from 7–9, unless the patient stakeholder group average score was ≥7.
After two Delphi rounds, there was consensus on three outcomes: frequency of bleeds, factor activity level, and duration of expression. Additional outcomes included after an in-person consensus meeting were chronic pain, mental health status, and utilization of the healthcare system (direct costs). Adverse events of interest were evaluated and separately reported.
Including the coreHEM COS in clinical development programs will ensure that relevant, consistent outcomes are available for decisions by HTA agencies, clinicians, and patients. This should result in faster access to novel, high-value therapies for appropriate patients.
OBJECTIVES/SPECIFIC AIMS: The objective of this study is to use machine Learning techniques to generate maps of epithelium and lumen density in MRI space. METHODS/STUDY POPULATION: Methods: We prospectively recruited 39 patients undergoing prostatectomy for this institutional review board (IRB) approved study. Patients underwent MP-MRI before prostatectomy on a 3T field strength MRI scanner (General Electric, Waukesha, WI, USA) using an endorectal coil. MP-MRI included field-of-view optimized and constrained undistorted single shot (FOCUS) diffusion weighted imaging with 10 b-values (b=0, 10, 25, 50, 80, 100, 200, 500, 1000, and 2000), dynamic contrast enhanced imaging, and T2-weighted imaging. T2 weighted images were intensity normalized and apparent diffusion coefficient maps were calculated. The dynamic contrast enhanced data was used to calculate the percent change in signal intensity before and after contrast injection. All images were aligned to the T2 weighted image. Robotic prostatectomy was performed 2 weeks after image acquisition. Prostate samples were sliced using a 3D printed slicing jig matching the slice profile of the T2 weighted image. Whole mount samples at 10 μm thickness were taken, hematoxylin and eosin stained, digitized, and annotated by a board certified pathologist. A total of 210 slides were included in this study. Lumen and epithelium were automatically segmented using a custom algorithm written in MATLAB. The algorithm was validated by comparing manual to automatic segmentation on 18 samples. Slides were aligned with the T2 weighted image using a nonlinear control point warping technique. Lumen and epithelium density and the expert annotation were subsequently transformed into MRI space. Co-registration was validated by applying a known warp to tumor masks noted by the pathologist and control point warping the whole mount slide to match the transform. Overlap was measured using a DICE coefficient. A learning curve was generated to determine the optimal number of patients to train the algorithm on. A PLS algorithm was trained on 150 random permutations of patients incrementing from 1 to 29 patients. Slides were stratified such that all slides from a single patient were in the same cohort. Three cohorts were generated, with tumor burden balanced across all cohort. A PLS algorithm was trained on 2 independent training sets (cohorts 1 and 2) and applied to cohort 3. The input vector consisted of MRI values and the target variable was lumen and epithelium density. The algorithm was trained lesion-wise. Trained PiCT models were applied to the test cohort voxel-wise to generate 2 new image contrasts. Mean lesion values were compared between high grade, low grade, and healthy tissue using an ANOVA. An ROC analysis was performed lesion-wise on the test set. RESULTS/ANTICIPATED RESULTS: Results: The segmentation accuracy validation revealed R=0.99 and R=0.72 (p<0.001) for lumen and epithelium, respectively. The co-registration accuracy revealed a 94.5% overlap. The learning curve stabilized at 10 patients with a root mean square error of 0.14, thus the size of the 2 independent training cohorts was set to 10, leaving 19 for the test cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: We present a technique for combining radiology and pathology with machine learning for generating predictive cytological topography (PiCT) maps of cellularity and lumen density prostate. The voxel-wise approach to mapping cellular features generates 2 new interpretable image contrasts, which can potentially increase confidence in diagnosis or guide biopsy and radiation treatment.
This article describes a formal proof of the Kepler conjecture on dense sphere packings in a combination of the HOL Light and Isabelle proof assistants. This paper constitutes the official published account of the now completed Flyspeck project.
Background Currently, the literature lacks reliable data regarding operative case volumes at Canadian neurosurgery residency programs. Our objective was to provide a snapshot of the operative landscape in Canadian neurosurgical training using the trainee-led Canadian Neurosurgery Research Collaborative. Methods: Anonymized administrative operative data were gathered from each neurosurgery residency program from January 1, 2014, to December 31, 2014. Procedures were broadly classified into cranial, spine, peripheral nerve, and miscellaneous procedures. A number of prespecified subspecialty procedures were recorded. We defined the resident case index as the ratio of the total number of operations to the total number of neurosurgery residents in that program. Resident number included both Canadian medical and international medical graduates, and included residents on the neurosurgery service, off-service, or on leave for research or other personal reasons. Results: Overall, there was an average of 1845 operative cases per neurosurgery residency program. The mean numbers of cranial, spine, peripheral nerve, and miscellaneous procedures were 725, 466, 48, and 193, respectively. The nationwide mean resident case indices for cranial, spine, peripheral nerve, and total procedures were 90, 58, 5, and 196, respectively. There was some variation in the resident case indices for specific subspecialty procedures, with some training programs not performing carotid endarterectomy or endoscopic transsphenoidal procedures. Conclusions: This study presents the breadth of neurosurgical training within Canadian neurosurgery residency programs. These results may help inform the implementation of neurosurgery training as the Royal College of Physicians and Surgeons residency training transitions to a competence-by-design curriculum.
Biochar may be useful for restoring or revitalizing degraded forest soils and help with carbon sequestration, nutrient leaching losses, and reducing greenhouse gas emissions. However, biochar is not currently widely used on forested lands across North America. This chapter provides an overview of several biochar experiments conducted in North America and discusses the feasibility of using in-woods mobile pyrolysis systems to convert excess forest biomass into biochar. Biochar may be applied to forest sites in order to positively influence soil properties (nutrient leaching, water holding capacity), but its biggest benefit may be in facilitating reforestation of degraded or contaminated sites, and in sequestering carbon in soils. The majority of data on biochar applications on forest sites focus on seedling responses and short-term impacts on nutrients, soil physical properties and microbial changes. Long-term field research is necessary to determine water use, carbon sequestration, nutrient use, and greenhouse gas emissions, and the subsequent alteration of forest growth and stand dynamics.
Palliative care and communication with cancer patients
Overview of palliative care
The World Health Organization defines palliative care as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual. Palliative care is focused on symptom relief and maximizing function, without necessarily impacting the natural history of the underlying illness. Bereavement support is integral to its mission as it views the patient and his or her loved ones as a unit of care. Palliative care is interdisciplinary, involving not only nurses and physicians, but chaplains, psychologists, social workers, and speech, physical, occupational, and other therapists. While palliative care has historic roots in the terminal care of cancer patients, its scope encompasses a wide variety of patients with non-malignant diseases. These include neurodegenerative disorders; advanced organ disease; and patients in critical care units. Ideally, palliative care is provided to patients with severe illnesses early in the course of their disease, alongside disease-modifying or curative therapy. As an illness progresses, and as disease-modifying or even life-prolonging interventions become less available, a patient's entire care may become palliative-focused. While much of the care of patients with life-threatening illness can be described as palliative, many patients will not require specialist palliative care, and basic competency in palliative care is important for clinicians across a variety of specialties and practice types.
Palliative medicine describes the physician's role in the aforementioned care model. Besides expert symptom assessment and treatment, palliative medicine physicians offer subspecialty expertise in determining prognosis and communication encounters with patients and families involving breaking bad news, establishing goals of medical care, and planning for the future in light of a life-threatening illness. The scope of practice of palliative medicine physicians varies by location and institution. Common settings include inpatient consultative palliative care services, acute inpatient palliative care wards, outpatient palliative care clinics, cancer pain and symptom management clinics, emergency departments, nursing home palliative care services, and hospice settings. Palliative care is increasing by number of programs and prevalence among adult and pediatric hospitals such that many cancer care providers will have access to palliative care specialists if needed.
The Full-sky Astrometric Mapping Explorer (FAME) is designed to perform an all-sky, astrometric survey with unprecedented accuracy. It will create a rigid astrometric catalog of 4 × 107 stars with 5 < mV < 15. For bright stars, 5 < mV < 9, FAME will determine positions and parallaxes accurate to < 50 μas, with proper motion errors < 50 μas/yr. For fainter stars, 9 < mV < 15, FAME will determine positions and parallaxes accurate to < 500 μas, with proper motion errors < 500 μas/yr. It will also collect photometric data on these 4 × 107 stars in four Sloan Digital Sky Survey colors. NASA selected FAME to be one of five MIDEX missions funded for a concept study. In October 1999, NASA selected FAME for launch in 2004 as the MIDEX-4 mission in its Explorer program.
This paper investigates the premise that long-term engagement in performance-focussed sports training may lead to significantly enhanced clinical outcomes for people with neurological impairments (NI). The minimum volume of moderate-intensity activity recommended for good health is 450 MET.minutes/week, although evidence from the general population indicates that outcomes may be enhanced by completing up to five times this volume (2250 MET.minutes/week) at vigorous (rather than moderate) intensity. Most studies evaluating physical activity interventions for people with NI deliver low volumes (<450 MET.minutes/week), which may explain why evidence for some clinical outcomes is weak. Athletes (with or without NI) who aim to achieve high-level sports performance undertake an increasingly large volume of vigorous intensity physical activity over several seasons. Evidence that people with NI may enhance clinical outcomes through performance-focussed sports training includes: evidence from studies investigating the benefits of high-intensity and/or high volume clinical exercise; scientific evidence from elite/high-level athletes; and anecdotal evidence from Paralympic athlete testimonials. Additionally, sports participants with NI may also accrue an important array of psychosocial benefits, including higher rates of employment, and higher satisfaction with life and social integration. Rigorous, prospective, longitudinal clinical monitoring of people with NI undertaking performance-focussed sports training are required to evaluate its clinical utility.
We prove a global Torelli theorem for pairs
is a smooth projective rational surface and
is a cycle of rational curves, as conjectured by Friedman in 1984. In addition, we construct natural universal families for such pairs.
The Nakhla meteorite represents basaltic rock from the martian upper crust, with reduced carbon indicative of the ingress of carbonaceous fluids. Study of a terrestrial analogue basalt with reduced carbon from the Ordovician of Northern Ireland shows that remote analysis could detect the carbon using Raman spectroscopy. Analysis of gases released by crushing detects methane-rich fluids in the basalt and especially in cross-cutting carbon-bearing veinlets. The results suggest that automated analysis on Mars could detect the reduced carbon, which may be derived from magmatic and/or meteoritic infall sources.