What Gets Measured, Gets Done: A Toolkit on Performance Measurement for Ending Homelessness

This toolkit provides an overview of performance measurement 101, including how to design a system and build it from scratch, using data to manage or change a homeless system, and understanding and implementing system-level performance measurement

Chronic graft-versus-host disease presenting as glossitis.

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Energy Performance Assessment of the Heating System Refurbishment on a School Building in Modena, Italy

Abstract The aim of this paper is the energy performance assessment of the school building Istituto Comprensivo "G. Marconi", located in Modena, Italy. This work describes the dynamic modeling of the building envelope and its heating system, carried out by means of the simulation software TRNSYS 17. According to the developed model, the school space heating loads, as well as the seasonal energy requirements, are evaluated by considering the actual heating system, which consists of gas-fired condensing boilers coupled to high temperature radiators. Then, the school heating system refurbishment is simulated: the paper evaluates the energy savings obtained by replacing boilers and radiators with an air-to-water multi-compressor heat pump, coupled to low temperature aluminum radiators, and by improving the system control strategy. Finally, the impact of the discussed energy saving measures on building energy performance and students thermal comfort is reported

Minimal Residual Disease Evaluation in Acute Myeloid Leukemia patients treated with Venetoclax and Hypomethylating Agents

Acute myeloid leukemia (AML) is a genetically heterogeneous malignant clonal disorder of the hematopoietic system. Treatment of older patients with AML is quite challenging, an older age is independently associated with an inferior outcome. Hypomethylating agents such as 5-azacytidine and decitabine, has shown to be a promising option for older patients with AML, who are not suitable candidates for intensive therapies. Venetoclax (VEN) is an oral, potent, and selective BCL2 inhibitor. Synergistic activity against myeloid malignancies is seen in vitro and in vivo with VEN in combination with lower intensity antileukemia therapy, such as low-dose cytarabine (LDAC) or hypomethylating agents (HMA). This project, aims to analyze the response of AML patients to Venetoclax and monitored by MRD assay (multiparameter flow cytometry or MFC) We will collect data on consecutive patients affected by de novo or secondary AML according to WHO 2016 criteria, in relapse or refractory phase of disease. Data will include clinical data and response data (minimal residual disease tested by multiparameter flow cytometry or MFC). The combined therapy of Venetoclax and HMA resulted in good responses, especially in chemo-refractory patients and allogeneic transplant candidates. The quality of the responses made it possible, in a good percentage, to achieve allogeneic transplantation in MRD-negativity conditions. The recurrence of treatment-associated neutropenia was the most frequent reason for temporary treatment discontinuation, consequently a document for the management of neutropenia was drawn up, derived from the various indications in the literature. Despite the good results achieved, resistance to venetoclax and the possibility of discontinuing treatment once deep and lasting complete remission has been achieved remain open questions

A peristomal plaque of sudden occurrence.

Koebner phenomenon regards the formation of a psoriatic lesion after a trauma, including tattoo, insect bite or other injuries. Although this manifestation is not specific for psoriasis, physicians should be aware because early recognition may be helpful in making the diagnosis when present

Angiokeratoma Circumscriptum Naeviforme Presenting as a Dark Warty Plaque on the Leg

45-year-old man presented with a large, dark, keratotic, warty, and friable plaque on the distal posterior aspect of the left leg (Figure 1, a). The patient reported that the lesion was not present at birth but had appeared approximately at the age of three as an erythematous patch that progressively grew over the time. During adolescence, the surface of the lesion became rough and warty and was easily traumatized due to its location, resulting in recurrent bleeding episodes over a period of years. For this reason, the patient requested lesion removal

The clonal evolution of two distinct T315I-positive BCR-ABL1 subclones in a Philadelphia-positive acute lymphoblastic leukemia failing multiple lines of therapy: a case report

BACKGROUND: The treatment of Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL) patients who harbor the T315I BCR-ABL1 mutation or who have two or more mutations in the same BCR-ABL1 molecule is particularly challenging since first and second-generation Tyrosine Kinase Inhibitors (TKIs) are ineffective. Ponatinib, blinatumomab, chemotherapy and transplant are the currently available options in these cases. CASE PRESENTATION: We here report the case of a young Ph+ ALL patient who relapsed on front-line dasatinib therapy because of two independent T315I-positive subclones, resulting from different nucleotide substitutions -one of whom never reported previously- and where additional mutant clones outgrew and persisted despite ponatinib, transplant, blinatumomab and conventional chemotherapy. Deep Sequencing (DS) was used to dissect the complexity of BCR-ABL1 kinase domain (KD) mutation status and follow the kinetics of different mutant clones across the sequential therapeutic approaches. CONCLUSIONS: This case presents several peculiar and remarkable aspects: i) distinct clones may acquire the same amino acid substitution via different nucleotide changes; ii) the T315I mutation may arise also from an 'act' to 'atc' codon change; iii) the strategy of temporarily replacing TKI therapy with chemo or immunotherapy, in order to remove the selective pressure and deselect aggressive mutant clones, cannot always be expected to be effective; iv) BCR-ABL1-mutated sub-clones may persist at very low levels (undetectable even by Deep Sequencing) for long time and then outcompete BCR-ABL1-unmutated ones becoming dominant even in the absence of any TKI selective pressure

Anomaly Detection from Low-dimensional Latent Manifolds with Home Environmental Sensors

Human Activity Recognition poses a significant challenge within Active and Assisted Living (AAL) systems, relying extensively on ubiquitous environmental sensor-based acquisition devices to detect user situations in their daily living. Environmental measurement systems deployed indoors yield multiparametric data in heterogeneous formats, which presents a challenge for developing Machine Learning-based AAL models. We hypothesized that anomaly detection algorithms could be effectively employed to create data-driven models for monitoring home environments and that the complex multiparametric indoor measurements can often be represented by a relatively small number of latent variables generated through Manifold Learning (MnL) techniques. We examined both linear (Principal Component Analysis) and non-linear (AutoEncoders) techniques for generating these latent spaces and the utility of core domain detection techniques for identifying anomalies within the resulting low-dimensional manifolds. We benchmarked this approach using three publicly available datasets (hh105, Aruba, and Tulum) and one proprietary dataset (Elioth) for home environmental monitoring. Our results demonstrated the following key findings: (a) Nonlinear manifold estimation techniques offer significant advantages in retrieving latent variables when compared to linear techniques; (b) The quality of the reconstruction of the original multidimensional recordings serves as an acceptable indicator of the quality of the generated latent spaces; (c) Domain detection identifies regions of normality consistent with typical individual activities in these spaces; And (d) the system effectively detects deviations from typical activity patterns and labels anomalies. This study lays the groundwork for further exploration of enhanced methods for extracting information from MnL data models and their application within the AAL and possibly other sectors

Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia

During the last few years many Checkpoint kinase 1/2 (Chk1/Chk2) inhibitors have been developed for the treatment of different type of cancers. In this study we evaluated the efficacy of the Chk 1/2 inhibitor prexasertib mesylate monohydrate in B-/T- cell progenitor acute lymphoblastic leukemia (ALL) as single agent and in combination with other drugs. The prexasertib reduced the cell viability in a dose and time dependent manner in all the treated cell lines. The cytotoxic activity was confirmed by the increment of apoptotic cells (Annexin V/Propidium Iodide staining), by the increase of \u3b3H2A.X protein expression and by the activation of different apoptotic markers (Parp-1 and pro-Caspase3 cleavage). Furthermore, the inhibition of Chk1 changed the cell cycle profile. In order to evaluate the chemo-sensitizer activity of the compound, different cell lines were treated for 24 and 48 hours with prexasertib in combination with other drugs (imatinib, dasatinib and clofarabine). The results from cell line models were strengthened in primary leukemic blasts isolated from peripheral blood of adult acute lymphoblastic leukemia patients. In this study we highlighted the mechanism of action and the effectiveness of prexasertib as single agent or in combination with other conventional drugs like imatinib, dasatinib and clofarabine in the treatment of B-/T-ALL