Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice

Giant coronary artery aneurysms in juvenile polyarteritis nodosa: a case report

Juvenile polyarteritis nodosa (PAN) is a rare, necrotizing vasculitis, primarily affecting small to medium-sized muscular arteries. Cardiac involvement amongst patients with PAN is uncommon and reports of coronary artery aneurysms in juvenile PAN are exceedingly rare. We describe a 16 year old girl who presented with fever, arthritis and two giant coronary artery aneurysms, initially diagnosed as atypical Kawasaki disease and treated with IVIG and methylprednisolone. Her persistent fevers, arthritis, myalgias were refractory to treatment, and onset of a vasculitic rash suggested an alternative diagnosis. Based on angiographic abnormalities, polymyalgia, hypertension and skin involvement, this patient met criteria for juvenile PAN. She was treated with six months of intravenous cyclophosphamide and high dose corticosteroids for presumed PAN related coronary vasculitis. Maintenance therapy was continued with azathioprine and the patient currently remains without evidence of active vasculitis. She remains on anticoagulation for persistence of the aneurysms. This case illustrates a rare and unusual presentation of giant coronary artery aneurysms in the setting of juvenile PAN

Blockchains and the commons

Blockchain phenomena is similar to the last century gold rush. Blockchain technologies are publicized as being the technical solution for fully decentralizing activities that were for centuries centralized such as administration and banking. Therefore, prominent socio-economical actors all over the world are attracted and ready to invest in these technologies. Despite their large publicity, blockchains are far from being a technology ready to be used in critical economical applications and scientists multiply their effort in warning about the risks of using this technology before understanding and fully mastering it. That is, a blockchain technology evolves in a complex environment where rational and irrational behaviors are melted with faults and attacks. This position paper advocates that the theoretical foundations of blockchains should be a cross research between classical distributed systems, distributed cryptography, self-organized micro-economies, game theory and formal methods. We discuss in the following a set of open research directions interesting in this context

In vivo isolated kidney perfusion with tumour necrosis factor α (TNF-α) in tumour-bearing rats

Isolated perfusion of the extremities with high-dose tumour necrosis factor α (TNF-α) plus melphalan leads to dramatic tumour response in patients with irresectable soft tissue sarcoma or multiple melanoma in transit metastases. We developed in vivo isolated organ perfusion models to determine whether similar tumour responses in solid organ tumours can be obtained with this regimen. Here, we describe the technique of isolated kidney perfusion. We studied the feasibility of a perfusion with TNF-α and assessed its anti-tumour effects in tumour models differing in tumour vasculature. The maximal tolerated dose (MTD) proved to be only 1 μg TNF-α. Higher doses appeared to induce renal failure and a secondary cytokine release with fatal respiratory and septic shock-like symptoms. In vitro, the combination of TNF-α and melphalan did not result in a synergistic growth-inhibiting effect on CC 531 colon adenocarcinoma cells, whereas an additive effect was observed on osteosarcoma ROS-1 cells. In vivo isolated kidney perfusion, with TNF-α alone or in combination with melphalan, did not result in a significant anti-tumour response in either tumour model in a subrenal capsule assay. We conclude that, because of the susceptibility of the kidney to perfusion with TNF-α, the minimal threshold concentration of TNF-α to exert its anti-tumour effects was not reached. The applicability of TNF-α in isolated kidney perfusion for human tumours seems, therefore, questionable. © 1999 Cancer Research Campaig

Kinetics of Host Cell Recruitment During Dissemination of Diffuse Malignant Peritoneal Mesothelioma

Diffuse malignant mesothelioma is an aggressive tumor which displays a median survival of 11.2 months and a 5-year survival of less than 5% emphasizing the need for more effective treatments. This study uses an orthotopic model of malignant mesothelioma established in syngeneic, immunocompetent C57Bl/6 mice which produce malignant ascites and solid tumors that accurately replicate the histopathology of the human disease. Host stromal and immune cell accumulation within malignant ascites and solid tumors was determined using immunofluorescent labeling with confocal microscopy and fluorescence-activated cell sorting. An expression profile of cytokines and chemokines was produced using quantitative real-time PCR arrays. Tumor spheroids and solid tumors show progressive growth and infiltration with host stromal and immune cells including macrophages, endothelial cells, CD4+ and CD8+ lymphocytes, and a novel cell type, myeloid derived suppressor cells (MDSCs). The kinetics of host cell accumulation and inflammatory mediator expression within the tumor ascites divides tumor progression into two distinct phases. The first phase is characterized by progressive macrophage and T lymphocyte recruitment, with a cytokine profile consistent with regulatory T lymphocytes differentiation and suppression of T cell function. The second phase is characterized by decreased expression of macrophage chemotactic and T-cell regulating factors, an increase in MDSCs, and increased expression of several cytokines which stimulate differentiation of MDSCs. This cellular and expression profile suggests a mechanism by which host immune cells promote diffuse malignant mesothelioma progression

Distributional Collision Resistance Beyond One-Way Functions

Distributional collision resistance is a relaxation of collision resistance that only requires that it is hard to sample a collision (x,y) where x is uniformly random and y is uniformly random conditioned on colliding with x. The notion lies between one-wayness and collision resistance, but its exact power is still not well-understood. On one hand, distributional collision resistant hash functions cannot be built from one-way functions in a black-box way, which may suggest that they are stronger. On the other hand, so far, they have not yielded any applications beyond one-way functions. Assuming distributional collision resistant hash functions, we construct constant-round statistically hiding commitment scheme. Such commitments are not known based on one-way functions and are impossible to obtain from one-way functions in a black-box way. Our construction relies on the reduction from inaccessible entropy generators to statistically hiding commitments by Haitner et al. (STOC \u2709). In the converse direction, we show that two-message statistically hiding commitments imply distributional collision resistance, thereby establishing a loose equivalence between the two notions. A corollary of the first result is that constant-round statistically hiding commitments are implied by average-case hardness in the class SZK (which is known to imply distributional collision resistance). This implication seems to be folklore, but to the best of our knowledge has not been proven explicitly. We provide yet another proof of this implication, which is arguably more direct than the one going through distributional collision resistance

Towards Non-Black-Box Separations of Public Key Encryption and One Way Function

Separating public key encryption from one way functions is one of the fundamental goals of complexity-based cryptography. Beginning with the seminal work of Impagliazzo and Rudich (STOC, 1989), a sequence of works have ruled out certain classes of reductions from public key encryption (PKE)---or even key agreement---to one way function. Unfortunately, known results---so called black-box separations---do not apply to settings where the construction and/or reduction are allowed to directly access the code, or circuit, of the one way function. In this work, we present a meaningful, non-black-box separation between public key encryption (PKE) and one way function. Specifically, we introduce the notion of $\textsf{BBN}^-$ reductions (similar to the $\textsf{BBN}\text{p}$ reductions of Baecher et al. (ASIACRYPT, 2013)), in which the construction $E$ accesses the underlying primitive in a black-box way, but wherein the universal reduction $R$ receives the efficient code/circuit of the underlying primitive as input and is allowed oracle access to the adversary $\textsf{Adv}$. We additionally require that the number of oracle queries made to $\textsf{Adv}$, and the success probability of $R$ are independent of the run-time/circuit size of the underlying primitive. We prove that there is no non-adaptive, $\textsf{BBN}^-$ reduction from PKE to one way function, under the assumption that certain types of strong one way functions exist. Specifically, we assume that there exists a regular one way function $f$ such that there is no Arthur-Merlin protocol proving that ``$z \not\in \textsf{Range}(f)$\u27\u27, where soundness holds with high probability over ``no instances,\u27\u27 $y \sim f(U_n)$, and Arthur may receive polynomial-sized, non-uniform advice. This assumption is related to the average-case analogue of the widely believed assumption $\textbf{coNP} \not\subseteq \textbf{NP}/\textbf{poly}$

Indistinguishable Proofs of Work or Knowledge

We introduce a new class of protocols called Proofs of Work or Knowledge (PoWorKs). In a PoWorK, a prover can convince a verifier that she has either performed work or that she possesses knowledge of a witness to a public statement without the verifier being able to distinguish which of the two has taken place. We formalise PoWorK in terms of three properties, completeness, f -soundness and indistinguishability (where f is a function that determines the tightness of the proof of work aspect) and present a construction that transforms 3-move HVZK protocols into 3-move public-coin PoWorKs. To formalise the work aspect in a PoWorK protocol we define cryptographic puzzles that adhere to certain uniformity conditions, which may also be of independent interest. We instantiate our puzzles in the random oracle (RO) model as well as via constructing “dense” versions of suitably hard one-way functions. We then showcase PoWorK protocols by presenting a number of applications. We first show how non-interactive PoWorKs can be used to reduce spam email by forcing users sending an e-mail to either prove to the mail server they are approved contacts of the recipient or to perform computational work. As opposed to previous approaches that applied proofs of work to this problem, our proposal of using PoWorKs is privacy-preserving as it hides the list of the receiver’s approved contacts from the mail server. Our second application, shows how PoWorK can be used to compose cryptocurrencies that are based on proofs of work (“Bitcoin-like”) with cryptocurrencies that are based on knowledge relations (these include cryptocurrencies that are based on “proof of stake”, and others). The resulting PoWorK-based cryptocurrency inherits the robustness properties of the underlying two systems while PoWorK-indistinguishability ensures a uniform population of miners. Finally, we show that PoWorK protocols imply straight-line quasi-polynomial simulatable arguments of knowledge and based on our construction we obtain an efficient straight-line concurrent 3-move statistically quasi-polynomial simulatable argument of knowledge