Neurasthenia Revisited: On Medically Unexplained Syndromes and the Value of Hermeneutic Medicine

 The rise of medically unexplained conditions like fibromyalgia and chronic fatigue syndrome in the United States looks remarkably similar to the explosion of neurasthenia diagnoses in the late nineteenth century. In this paper, I argue the historical connection between neurasthenia and today’s medically unexplained conditions hinges largely on the uncritical acceptance of naturalism in medicine. I show how this cultural acceptance shapes the way in which we interpret and make sense of nervous distress while, at the same time, neglecting the unique social and historical forces that continue to produce it. I draw on the methods of hermeneutic philosophy to expose the limits of naturalism and forward an account of health and illness that acknowledges the extent to which we are always embedded in contexts of meaning that determine how we experience and understand our suffering. 

Acceleration and Time Pathologies

In his Contributions to Philosophy, Martin Heidegger (1999) introduces ‘acceleration’ as one of the three symptoms – along with ‘calculation’ and the ‘outbreak of massiveness’ – of our technological way of ‘being-in-the-world’. In this article, I unpack the relationship between these symptoms and draw a twofold conclusion. First, interpreting acceleration in terms of time pathologies, I suggest the self is becoming increasingly fragmented and emotionally overwhelmed from chronic sensory arousal and time pressure. This experience makes it difficult for us to qualitatively distinguish what matters to us in our everyday lives, resulting in a pervasive cultural mood of indifference, what Heidegger (1995) calls ‘profound boredom’. Second, by drawing on Heidegger's hermeneutic method, I argue that the practice of mainstream psychology, by adopting the reductive methodology of the empirical sciences, largely ignores our accelerated socio-historical situation, resulting in therapeutic models that have a tendency to construct and perpetuate the very pathologies the psychologist is seeking to treat

The VENUSS prognostic model to predict disease recurrence following surgery for non-metastatic papillary renal cell carcinoma: development and evaluation using the ASSURE prospective clinical trial cohort

Abstract: Background: The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery. Methods: We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1–4, N0–1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups. Results: We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups. Conclusions: We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of superhump period are found to be composed of three distinct stages: early evolutionary stage with a longer superhump period, middle stage with systematically varying periods, final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods less than 0.08 d show positive period derivatives. Contrary to the earlier claim, we found no clear evidence for variation of period derivatives between superoutburst of the same object. We present an interpretation that the lengthening of the superhump period is a result of outward propagation of the eccentricity wave and is limited by the radius near the tidal truncation. We interpret that late stage superhumps are rejuvenized excitation of 3:1 resonance when the superhumps in the outer disk is effectively quenched. Many of WZ Sge-type dwarf novae showed long-enduring superhumps during the post-superoutburst stage having periods longer than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently, mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives and are excellent candidate for the systems around or after the period minimum of evolution of cataclysmic variables (abridged).Comment: 239 pages, 225 figures, PASJ accepte

The computational complexity of asymptotic problems I: Partial orders

The class of partial orders is shown to have 0-1 laws for first-order logic and for inductive fixed-point logic, a logic which properly contains first-order logic. This means that for every sentence in one of these logics the proportion of labeled (or unlabeled) partial orders of size n satisfying the sentence has a limit of either 0 or 1 as n goes to [infinity]. This limit, called the asymptotic probability of the sentence, is the same for labeled and unlabeled structures. The computational complexity of the set of sentences with asymptotic probability 1 is determined. For first-order logic, it is PSPACE-complete. For inductive fixed-point logic, it is EXPTIME-complete.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27185/1/0000188.pd

Blind Benchmark Exercise for Spent Nuclear Fuel Decay Heat

The decay heat rate of five spent nuclear fuel assemblies of the pressurized water reactor type were measured by calorimetry at the interim storage for spent nuclear fuel in Sweden. Calculations of the decay heat rate of the five assemblies were performed by 20 organizations using different codes and nuclear data libraries resulting in 31 results for each assembly, spanning most of the current state-of-the-art practice. The calculations were based on a selected subset of information, such as reactor operating history and fuel assembly properties. The relative difference between the measured and average calculated decay heat rate ranged from 0.6% to 3.3% for the five assemblies. The standard deviation of these relative differences ranged from 1.9% to 2.4%

Hyperpolarized¹³C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma—A Proof of Principle Study

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p &lt; 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.</jats:p

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer