Rethinking feasibility analysis for urban development: a multidimensional decision support tool

Large-scale urban development projects featured over the past thirty years have shown some critical issues related to the implementation phase. Con-sequently, the current practice seems oriented toward minimal and wide-spread interventions meant as urban catalyst. This planning practice might solve the problem of limited reliability of large developments’ feasibility studies, but it rises an evaluation demand related to the selection of coali-tion of projects within a multidimensional and multi-stakeholders deci-sion-making context. This study aims to propose a framework for the generation of coalitions of elementary actions in the context of urban regeneration processes and for their evaluation using a Multi Criteria Decision Analysis approach. The proposed evaluation framework supports decision makers in exploring dif-ferent combinations of actions in the context of urban interventions taking into account synergies, i.e. positive or negative effects on the overall per-formance of an alternative linked to the joint realization of specific pairs of actions. The proposed evaluation framework has been tested on a pilot case study dealing with urban regeneration processes in the city of Milan (Italy)

La gestione del rischio di ondate di calore e allagamenti in ambiente urbano: un modello applicativo

Le citta sono chiamate a rispondere alle emergenze indotte dal cambiamento climatico (CC). Laddove il paradigma della mitigazione (avente come obiettivo la riduzione degli impatti delle attivita umane nei confronti de! clima) e frutto di accordi internazionali, nell'adattare le citta alle esternalita causate dal CC, le sfide assumono una connotazione locale. L'adattamento al CC e pertanto prima di tutto un concerto spaziale, territoriale, un nuovo paradigma che invita alla rielaborazione delle teorie e degli strumenti de! piano e de! progetto urbano. Adattare le citta nei confronti delle esternalita climatiche come ondate di calore e piogge intense, costringe l'urbanistica alla previsione e alla gestione di rischi locali incerti. La ricerca si concentra nella sperimentazione di un processo di planning che, partendo dall'analisi, favorisca una maggiore conoscenza de! territorio, mediante l'integrazione con !'information and communication technology (ICT). Lo studio e orientato 1) nello sviluppo di processi di produzione di informazione urbana e ambientale (mediante Remote Sensing Analysis), 2) valutazione di modelli di integrazione e interpolazione delle informazioni create con le informazioni esistenti 3) composizione de! processo di analisi de! rischio urbana al CC, a scala di quartiere. Il lavoro e stato arricchito dalle esperienze prodotte dalla partecipazione di tre Progetti Europei e da un periodo di visiting alla Drexel University di Philadelphia con una sperimentazione della metodologia sulla citta di New York

Past, present, and future strategies for enhanced assessment of embryo's genome and reproductive competence in women of advanced reproductive age

Recent advancements in genomic analysis allow testing of an increasing number of genetic features in human preimplantation embryos. Typical single gene mutation and whole chromosomes testing can now be integrated with assessment of mitochondrial DNA and polygenic conditions. Diagnostic expansion into epigenetic and transcriptomic assessment in the near future are potential technological targets which may improve the prognostic outlook of patients of advanced reproductive age and overall in vitro fertilization (IVF) treatment outcomes. In this review, we discuss the technological progress of recent years and their future applications in preimplantation genetic testing in IVF

Cerebral deficiency of vitamin B5 (D-pantothenic acid; pantothenate) as a potentially-reversible cause of neurodegeneration and dementia in sporadic Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of age-related neurodegeneration and dementia, and there are no available treatments with proven disease-modifying actions. It is therefore appropriate to study hitherto-unknown aspects of brain structure/function in AD to seek alternative disease-related mechanisms that might be targeted by new therapeutic interventions with disease-modifying actions. During hypothesis-generating metabolomic studies of brain, we identified apparent differences in levels of vitamin B5 between AD cases and controls. We therefore developed a method based on gas chromatography-mass spectrometry by which we quantitated vitamin B5 concentrations in seven brain regions from nine AD cases and nine controls. We found that widespread, severe cerebral deficiency of vitamin B5 occurs in AD. This deficiency was worse in those regions known to undergo severe damage, including the hippocampus, entorhinal cortex, and middle temporal gyrus. Vitamin B5 is the obligate precursor of CoA/acetyl-CoA (acetyl-coenzyme A), which plays myriad key roles in the metabolism of all organs, including the brain. In brain, acetyl-CoA is the obligate precursor of the neurotransmitter acetylcholine, and the complex fatty-acyl groups that mediate the essential insulator role of myelin, both processes being defective in AD; moreover, the large cerebral vitamin B5 concentrations co-localize almost entirely to white matter. Vitamin B5 is well tolerated when administered orally to humans and other mammals. We conclude that cerebral vitamin B5 deficiency may well cause neurodegeneration and dementia in AD, which might be preventable or even reversible in its early stages, by treatment with suitable oral doses of vitamin B5

Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington's disease

<p>Abstract</p> <p>Backgound</p> <p>No disease modifying treatment currently exists for Huntington's disease (HD), a fatal neurodegenerative disorder characterized by the formation of amyloid-like aggregates of the mutated huntingtin protein. Curcumin is a naturally occurring polyphenolic compound with Congo red-like amyloid binding properties and the ability to cross the blood brain barrier. CAG140 mice, a knock-in (KI) mouse model of HD, display abnormal aggregates of mutant huntingtin and striatal transcriptional deficits, as well as early motor, cognitive and affective abnormalities, many months prior to exhibiting spontaneous gait deficits, decreased striatal volume, and neuronal loss. We have examined the ability of life-long dietary curcumin to improve the early pathological phenotype of CAG140 mice.</p> <p>Results</p> <p>KI mice fed a curcumin-containing diet since conception showed decreased huntingtin aggregates and increased striatal DARPP-32 and D1 receptor mRNAs, as well as an amelioration of rearing deficits. However, similar to other antioxidants, curcumin impaired rotarod behavior in both WT and KI mice and climbing in WT mice. These behavioral effects were also noted in WT C57Bl/6 J mice exposed to the same curcumin regime as adults. However, neither locomotor function, behavioral despair, muscle strength or food utilization were affected by curcumin in this latter study. The clinical significance of curcumin's impairment of motor performance in mice remains unclear because curcumin has an excellent blood chemistry and adverse event safety profile, even in the elderly and in patients with Alzheimer's disease.</p> <p>Conclusion</p> <p>Together with this clinical experience, the improvement in several transgene-dependent parameters by curcumin in our study supports a net beneficial effect of dietary curcumin in HD.</p

Substantively Lowered Levels of Pantothenic Acid (Vitamin B5) in Several Regions of the Human Brain in Parkinson’s Disease Dementia

From MDPI via Jisc Publications RouterHistory: accepted 2021-08-23, pub-electronic 2021-08-25Publication status: PublishedFunder: Endocore Research Associates, NZ; Grant(s): 60147, 3626585; 3702766, JXU058, UOAX0815Funder: Maurice and Phyllis Paykel Trust; Grant(s): 3627036Funder: Maurice Wilkins Centre for Molecular Biodiscovery; Grant(s): 9341-3622506Funder: Oakley Mental Health Research Foundation; Grant(s): 3456030; 3627092; 3701339; 3703253; 3702870Funder: Neurological Foundation of New Zealand; Grant(s): N/AFunder: Medical Research Council; Grant(s): MR/L010445/1 and MR/L011093/1Funder: Alzheimer’s Research UK; Grant(s): ARUK-PPG2014B-7Pantothenic acid (vitamin B5) is an essential trace nutrient required for the synthesis of coenzyme A (CoA). It has previously been shown that pantothenic acid is significantly decreased in multiple brain regions in both Alzheimer’s disease (ADD) and Huntington’s disease (HD). The current investigation aimed to determine whether similar changes are also present in cases of Parkinson’s disease dementia (PDD), another age-related neurodegenerative condition, and whether such perturbations might occur in similar regions in these apparently different diseases. Brain tissue was obtained from nine confirmed cases of PDD and nine controls with a post-mortem delay of 26 h or less. Tissues were acquired from nine regions that show high, moderate, or low levels of neurodegeneration in PDD: the cerebellum, motor cortex, primary visual cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons. A targeted ultra–high performance liquid chromatography—tandem mass spectrometry (UHPLC-MS/MS) approach was used to quantify pantothenic acid in these tissues. Pantothenic acid was significantly decreased in the cerebellum (p = 0.008), substantia nigra (p = 0.02), and medulla (p = 0.008) of PDD cases. These findings mirror the significant decreases in the cerebellum of both ADD and HD cases, as well as the substantia nigra, putamen, middle frontal gyrus, and entorhinal cortex of HD cases, and motor cortex, primary visual cortex, hippocampus, middle temporal gyrus, cingulate gyrus, and entorhinal cortex of ADD cases. Taken together, these observations indicate a common but regionally selective disruption of pantothenic acid levels across PDD, ADD, and HD

Midterm follow-up after embolization of intracranial aneurysms proximal to the circle of Willis with the Silk Vista flow diverter: the I-MAMA registry

Purpose: The aim of this registry was to assess technical success, procedural safety and mid- to long-term follow-up results of the Silk Vista “Mama” (SVM) flow diverter (BALT, Montmorency, France) for the treatment of proximal intracranial aneurysms. Methods: Between August 2020 and March 2022, data from nine Italian neurovascular centres were collected. Data included patients’ clinical presentation, aneurysms’ size, location and status, technical details, overall complications and mid- to long-term angiographic follow-up. Results: Forty-eight aneurysms in 48 patients were treated using the SVM. Most aneurysms were small (≤ 10 mm: no. 29, 60%) and unruptured (no. 31, 65%); 13 aneurysms were recurrent after coiling or clipping. 37/48 aneurysms involved the internal carotid artery (77%). Optimal opening and complete wall apposition of the device were achieved in 46 out of 48 cases (96%). Four intra- or periprocedural complications occurred (two thrombotic complications successfully resolved, one cerebellar ischemia, one perirenal hematoma), without new neurological deficit. No significant intra-stent stenosis or stent displacement was observed during follow-up. No FD-related morbidity nor mortality was reported. At midterm (6–12 months) to long-term (> 12 months) follow-up, complete aneurysm occlusion (OKM D) was achieved in 76% of cases. Eighty-eight percent of patients had complete aneurysm occlusion or entry remnant (OKM D + C). Conclusions: Our experience suggests that the new generation of low-profile SVM flow diverter for the treatment of proximal intracranial aneurysms is safe and effective, with low rates of intraprocedural complications and acceptable mid- to long-term occlusion rate

Past, Present, and Future Strategies for Enhanced Assessment of Embryo's Genome and Reproductive Competence in Women of Advanced Reproductive Age

Recent advancements in genomic analysis allow testing of an increasing number of genetic features in human preimplantation embryos. Typical single gene mutation and whole chromosomes testing can now be integrated with assessment of mitochondrial DNA and polygenic conditions. Diagnostic expansion into epigenetic and transcriptomic assessment in the near future are potential technological targets which may improve the prognostic outlook of patients of advanced reproductive age and overall in vitro fertilization (IVF) treatment outcomes. In this review, we discuss the technological progress of recent years and their future applications in preimplantation genetic testing in IVF

Mechanism of Human Papillomavirus Binding to Human Spermatozoa and Fertilizing Ability of Infected Spermatozoa

Human papillomaviruses (HPVs) are agents of the most common sexually transmitted diseases in females and males. Precise data about the presence, mechanism of infection and clinical significance of HPV in the male reproductive tract and especially in sperm are not available. Here we show that HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm exposed to HPV L1 capsid protein are capable to penetrate the oocyte and transfer the virus into oocytes, in which viral genes are then activated and transcribed. These data show that sperm might function as vectors for HPV transfer into the oocytes, and open new perspectives on the role of HPV infection in males and are particularly intriguing in relation to assisted reproduction techniques