Cancer stage at diagnosis is important information for management and treatment of individual patients as well as in epidemiological studies to evaluate effectiveness of health care system in ...managing cancer patients. Population‐based studies to examine international disparities on cancer survival by stage, however, has been challenging due to the lack of international standardization on recording stage information and variation in stage completeness across regions and countries. The International Cancer Benchmarking Partnership (ICBP) previously assessed the availability and comparability of staging information for colorectal, lung, female breast and ovarian cancers. Stage conversion algorithms were developed to aggregate and map all stage information into a single staging system to allow international comparison by stage at diagnosis. In this article, we developed stage conversion algorithms for three additional cancers, namely oesophageal, gastric and pancreatic cancers. We examined all stage information available, evaluated stage completeness, applied each stage conversion algorithm, and assessed the magnitude of misclassification using data from six Canadian cancer registries (Alberta, Manitoba, Newfoundland, Nova Scotia, Prince Edward Island and Saskatchewan). In addition, we discussed five recommendations for registries to improve international cancer survival comparison by stage: (a) improve collection and completeness of staging data; (b) promote a comparable definition for stage at diagnosis; (c) promote the use of a common stage classification system; (d) record versions of staging classifications and (e) use multiple data sources for valid staging data.
Histotripsy is a therapy that focuses short-duration, high-amplitude pulses of ultrasound to incite a localized cavitation cloud that mechanically breaks down tissue. To investigate the mechanism of ...cloud formation, high-speed photography was used to observe clouds generated during single histotripsy pulses. Pulses of 5-20 cycles duration were applied to a transparent tissue phantom by a 1-MHz spherically focused transducer. Clouds initiated from single cavitation bubbles that formed during the initial cycles of the pulse, and grew along the acoustic axis opposite the propagation direction. Based on these observations, we hypothesized that clouds form as a result of large negative pressure generated by the backscattering of shockwaves from a single bubble. The positive-pressure phase of the wave inverts upon scattering and superimposes on the incident negative-pressure phase to create this negative pressure and cavitation. The process repeats with each cycle of the incident wave, and the bubble cloud elongates toward the transducer. Finite-amplitude propagation distorts the incident wave such that the peak-positive pressure is much greater than the peak-negative pressure, which exaggerates the effect. The hypothesis was tested with two modified incident waves that maintained negative pressure but reduced the positive pressure amplitude. These waves suppressed cloud formation which supported the hypothesis.
We use a microwave field to control the quantum state of optical photons stored in a cold atomic cloud. The photons are stored in highly excited collective states (Rydberg polaritons) enabling both ...fast qubit rotations and control of photon-photon interactions. Through the collective read-out of these pseudospin rotations it is shown that the microwave field modifies the long-range interactions between polaritons. This technique provides a powerful interface between the microwave and optical domains, with applications in quantum simulations of spin liquids, quantum metrology and quantum networks.
Recent theoretical work in developmental psychology suggests that humans are predisposed to align their mental states with those of other individuals. One way this manifests is in
; that is, ...intentional communication aimed at aligning individuals' mental states with respect to events in their shared environment. This idea has received strong empirical support. The purpose of this paper is to extend this account by proposing an integrative model of the biobehavioral dynamics of cooperative communication. Our formulation is based on
. Active inference suggests that action-perception cycles operate to minimize uncertainty and optimize an individual's internal model of the world. We propose that humans are characterized by an evolved
that their mental states are aligned with, or similar to, those of conspecifics (i.e., that 'we are the same sort of creature, inhabiting the same sort of niche'). The use of cooperative communication emerges as the principal means to gather evidence for this belief, allowing for the development of a shared narrative that is used to disambiguate interactants' (hidden and inferred) mental states. Thus, by using cooperative communication, individuals effectively attune to a hermeneutic niche composed, in part, of others' mental states; and, reciprocally, attune the niche to their own ends via epistemic niche construction. This means that niche construction enables features of the niche to encode precise, reliable cues about the
or
of certain action policies (e.g., the utility of using communicative constructions to disambiguate mental states, given expectations about shared prior beliefs). In turn, the alignment of mental states (prior beliefs) enables the emergence of a novel, contextualizing scale of
dynamics that encompasses the actions and mental states of the ensemble of interactants and their shared environment. The dynamics of this contextualizing layer of cultural organization feedback, across scales, to constrain the variability of the prior expectations of the individuals who constitute it. Our theory additionally builds upon the active inference literature by introducing a new set of neurobiologically plausible computational hypotheses for cooperative communication. We conclude with directions for future research.
When someone masters a skill, their performance looks to us like second nature: it looks as if their actions are smoothly performed without explicit, knowledge-driven, online monitoring of their ...performance. Contemporary computational models in motor control theory, however, are
instructionist
: that is, they cast skillful performance as a knowledge-driven process. Optimal motor control theory (OMCT), as representative
par excellence
of such approaches, casts skillful performance as an instruction, instantiated in the brain, that needs to be executed—a motor command. This paper aims to show the limitations of such instructionist approaches to skillful performance. We specifically address the question of whether the assumption of control-theoretic models is warranted. The first section of this paper examines the instructionist assumption, according to which skillful performance consists of the execution of theoretical instructions harnessed in motor representations. The second and third sections characterize the implementation of motor representations as motor commands, with a special focus on formulations from OMCT. The final sections of this paper examine predictive coding and active inference—behavioral modeling frameworks that descend, but are distinct, from OMCT—and argue that the instructionist, control-theoretic assumptions are ill-motivated in light of new developments in active inference.
With increasing use of high-power laser settings for lithotripsy, the potential exists to induce thermal tissue damage. In vitro studies have demonstrated that temperature elevation sufficient to ...cause thermal tissue damage can occur with certain laser and irrigation settings. The objective of this pilot study was to measure caliceal fluid temperature during high-power laser lithotripsy in an in vivo porcine model.
Four female pigs (30-35 kg) were placed under general anesthesia and positioned supine. Retrograde ureteroscopy with entry into upper or middle calices was performed. Thermocouples were placed into the calix by open exposure and puncture of the kidney or retrograde alongside the ureteroscope. A 242 μm laser fiber was positioned in the center of the calix and activated (0.5 J, 80 Hz, 40 W) for 60 seconds with high, medium, or no irrigation delivered in each trial. Finite element simulations of laser-induced heating in a renal calix were also performed.
Peak temperatures of 84.8°C, 63.9°C, and 43.6°C were recorded for no, medium, and high irrigation, respectively. Mean time to reach threshold of thermal injury (t
of 120 minutes) was 12.7 and 17.8 seconds for no and medium irrigation. Thermal damage thresholds were not reached in high-irrigation trials. Numerical simulations revealed similar results with peak spatial average fluid temperatures of >100°C, 58.5°C, and 37.5°C during 60 seconds of laser activation for 0.1, 15, and 40 mL/minute irrigation, respectively.
High-power holmium laser settings (40 W) can induce potentially injurious temperatures in the porcine in vivo model, particularly with slower irrigation rates. Characterization of thermal dose across a broader range of laser parameter settings is underway to map out the thermal safety envelope.
Abstract
Objectives
Laboratory testing and the measurement of appropriate biomarkers play a critical role in managing patients with coronavirus disease 2019 (COVID-19), allowing for disease ...diagnosis, monitoring progression, prognostication, prediction of treatment response, and risk stratification. We sought to characterize these effects on a more detailed, mechanistic level.
Methods
We reviewed the literature and identified a multitude of reports that describe the unique effects of this virus and its devastating consequences to multiple organ systems in COVID-19 patients.
Results
There are specific alterations in biomarkers related to coagulation, depopulation of T-cell subtypes, the cytokine storm and inflammation, and kidney and cardiac dysfunction.
Conclusions
Laboratory measurement of specific parameters and the use of appropriate prognostic, predictive, and monitoring biomarkers afford clinicians the ability to make informed medical decisions and guide therapy for patients afflicted with this dreaded disease.
Cancers occurring in children in Africa are often underdiagnosed, or at best diagnosed late. As a result, survival is poor, even for cancers considered ‘curable’. With limited population‐level data, ...understanding the actual burden and survival from childhood cancers in Africa is difficult. In this study, we aimed at providing survival estimates for the most common types of cancers affecting children aged 0–14 years, in three population‐based Eastern African registries; Harare, Zimbabwe (Kaposi sarcoma, Wilms tumour (WT), non‐Hodgkin lymphoma (NHL), retinoblastoma, and acute lymphocytic leukaemia (ALL)), Kampala, Uganda (Burkitt lymphoma, Kaposi sarcoma, WT, and retinoblastoma), and Nairobi, Kenya (ALL, retinoblastoma, WT, Burkitt lymphoma, and Hodgkin lymphoma). We included cases diagnosed within the years 1998–2009 and followed up till the end of 2011. We estimated the observed and relative survival at 1, 3, and 5 years after diagnosis. We studied 627 individual patient records. Median follow‐up ranged from 2.2 months for children with Kaposi sarcoma in Harare to 30.2 months for children with ALL in Nairobi. The proportion of children lost to follow‐up was highest in the first year after diagnosis. In Harare and Kampala, the 5‐year relative survival was <46% for all cancer types. The 5‐year relative survival was best for children in Nairobi, though with wider confidence intervals. Survival from childhood cancers in Africa is still poor, even for cancers with good prognosis and potential for cure. Supporting cancer detection, treatment, and registration activities could help improve survival chances for children with cancers in Africa.
What's new?
Previous analyses of hospital and clinic data suggest that survival rates for childhood cancer patients in Africa are low. Little is actually known, however, about childhood cancer survival in the general population, owing to a lack of data. Here, the authors analyzed survival data for the most common childhood cancers from three population‐based cancer registries in East Africa. At five years after diagnosis, relative survival was less than 46 percent for children in Harare and Kampala, while relative survival was higher for children in Nairobi. Many children, however, were lost to follow‐up within the first year of diagnosis.
Mycolicibacter kumamotonensis is a slowly growing, non-chromogenic non-tuberculous mycobacteria (NTM) that was initially distinguished from the M. terrae complex in 2006. Since then it has been ...rarely reported as the cause of pulmonary and soft-tissue infections in both immunocompromised and immunocompetent patients.
We present a case of severe pulmonary disease due to Mycolicibacter kumamotonensis in a 57-year-old male who was immunocompetent at time of diagnosis, with a history of interstitial lung disease and a prior diagnosis of tuberculosis (TB). After initial treatment for TB in 2017, his condition stabilized until a recurrence in September 2021, leading to an evaluation for lung transplant in the setting of pulmonary fibrosis and emphysema which led to the identification of Mycolicibacter kumamotonensis. A lung transplant was completed, and the patient was successfully treated with a combination of Ethambutol, Azithromycin, and Rifabutin.
This represents the first case reported of M. kumamotonensis in a patient undergoing lung transplant, and the first case with rapid culture growth during identification of the organism (4 days). This report highlights the need for consideration of M. kumamotonensis as a pathogen in humans, with the potential for rapid growth in liquid media, and the importance of early identification to inform empiric therapy.
Essential tremor is a common brain disorder affecting millions of people, yet the neuronal mechanisms underlying this prevalent disease remain elusive. Here, we showed that conditional deletion of ...synaptotagmin-2, the fastest Ca2+ sensor for synaptic neurotransmitter release, from parvalbumin neurons in mice caused an action tremor syndrome resembling the core symptom of essential tremor patients. Combining brain region-specific and cell type-specific genetic manipulation methods, we found that deletion of synaptotagmin-2 from excitatory parvalbumin-positive neurons in cerebellar nuclei was sufficient to generate an action tremor. The synaptotagmin-2 deletion converted synchronous into asynchronous neurotransmitter release in projections from cerebellar nuclei neurons onto gigantocellular reticular nucleus neurons, which might produce an action tremor by causing signal oscillations during movement. The tremor was rescued by completely blocking synaptic transmission with tetanus toxin in cerebellar nuclei, which also reversed the tremor phenotype in the traditional harmaline-induced essential tremor model. Using a promising animal model for action tremor, our results thus characterized a synaptic circuit mechanism that may underlie the prevalent essential tremor disorder.
PDF
