Developing financial markets

Central banks have an interest in well-functioning money markets, foreign exchange markets, and secondary markets for government securities. Efficient financial markets support both the monetary stability and financial stability goals of the central bank; and more broadly should benefit economic development. Well-functioning money markets support the transmission of an interest-rate based monetary policy and can provide information to the central bank. Liquid foreign exchange markets can help to stabilise the exchange rate and reduce transaction costs in cross-border trade and transfers. The development of these markets will support the later introduction of related financial markets such as repo and derivatives, which should in turn lead to improved risk management and financial stability, thereby enhancing economic welfare. Liquidity and price stability in short-term interest rate markets can support market-making, and thus liquidity in the securities markets. This in turn should reduce the cost of issuance for the government and other fixed-interest issuers. Indeed the secondary market for government securities may act as a catalyst for wider fixed income securities markets development: its yield curve is the benchmark for the pricing of the private sector credit. The advancement of these markets should be accompanied by the development of the appropriate market infrastructure such as robust payment and settlement systems and supportive legal framework. Many developing economies are characterised by illiquidity in these core markets, and in most cases a surplus of central bank money, in the form of excess commercial bank balances with the central bank. This handbook will look at what the central bank, and the Ministry of Finance as issuer of government securities, could do (and in some cases should not do) in support of the development of these markets.Developing financial markets

Monetary Operations

Monetary operations refer to the implementation of monetary policy – ensuring that a central bank’s policy decision has the intended impact on financial markets, and on the economy more generally. For operational purposes the day-to-day tactical target is usually to achieve a particular level of interest rates or the exchange rate; and the most efficient instruments are those which best complement the workings of a market system. This Handbook examines the various different instruments: open market operations; standing facilities; and both required reserves (which have some of the characteristics of direct controls), and voluntary or contractual reserves. Open market operations are undertaken at the initiative of the central bank, whereas standing facilities are used at the initiative of the commercial banks. Participation in both is voluntary at the level of individual banks, whereas in most countries reserve requirements are an administrative imposition on all banks - albeit one which, through averaging, allows them a degree of day-to-day flexibility. Monetary instruments are not only used to implement monetary policy; they are also used for liquidity management. This is an essential part of the central bank’s operations, in order to prevent the short-term uncertainty and price volatility which day-to-day swings in market liquidity would otherwise cause. The Handbook therefore also considers liquidity forecasting and management issues.Monetary Operations

Cardiopulmonary phenotype associated with human PHD2 mutation.

Oxygen-dependent regulation of the erythropoietin gene is mediated by the hypoxia-inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a family of oxygen-dependent prolyl hydroxylase domain (PHD) proteins, promoting its association with the von Hippel-Lindau (VHL) ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is scarce, the PHD enzymes are inactivated, leading to HIF accumulation and upregulation not only of erythropoietin expression, but also the expression of hundreds of other genes, including those coordinating cardiovascular and ventilatory adaptation to hypoxia. Nevertheless, despite the identification of over 50 mutations in the PHD-HIF-VHL pathway in patients with previously unexplained congenital erythrocytosis, there are very few reports of associated cardiopulmonary abnormalities. We now report exaggerated pulmonary vascular and ventilatory responses to acute hypoxia in a 35-year-old man with erythrocytosis secondary to heterozygous mutation in PHD2, the most abundant of the PHD isoforms. We compare this phenotype with that reported in patients with the archetypal disorder of cellular oxygen sensing, Chuvash polycythemia, and discuss the possible clinical implications of our findings, particularly in the light of the emerging role for small molecule PHD inhibitors in clinical practice

Diagnosis and surgical removal of brain abscesses in a juvenile alpaca

Case Description—A 1-month-old female alpaca was examined because of progressive clinical signs consistent with an intracranial lesion.<p></p> Clinical Findings—Clinical signs included signs of depression, lethargy, tetraparesis, and neck weakness. Two large isointense intracranial masses could be seen on T1-weighted magnetic resonance images. On T2-weighted images, the masses contained concentric rings of hypointense and hyperintense material.<p></p> Treatment and Outcome—2 abscesses were removed via a craniotomy that incorporated removal of the sagittal crest and surrounding skull and transection of the sagittal sinus. The bony deficit was replaced with polypropylene mesh. The alpaca recovered within 2 weeks and was fully integrated into the herd within 1 month after surgery.<p></p> Clinical Relevance—Findings indicated that surgical removal is a feasible means of successfully treating intracranial abscesses in juvenile alpacas

Delivering word retrieval therapies for people with aphasia in a virtual communication environment

Background: Delivering therapy remotely, via digital technology, can enhance provision for people with aphasia. EVA Park is a multi-user virtual island that can be used for such delivery. The first EVA Park study showed that daily language stimulation delivered via the platform improved functional communication and was positively received by users (Marshall et al, 2016; Amaya et al, 2018). This paper reports two single case studies, evaluating its capacity to deliver targeted language interventions. The first employed therapy for noun retrieval, using cued picture naming and modified Sematic Feature Analysis. The second employed modified Verb Network Strengthening Treatment (VNeST). Aims: This study aimed to determine if treatment delivery was feasible in EVA Park, as assessed by participant compliance, treatment fidelity and participants’ views. It explored the impact of the therapies on treated and untreated word production, connected speech and functional communication. Methods & Procedures: Two participants with aphasia each received 20 sessions of individual therapy in EVA Park, delivered over 5 weeks. Feasibility was assessed by measuring compliance with the therapy regime, recording and checking the fidelity of 20% of treatment sessions, and using post therapy interviews to explore participant views. Treatment outcomes were evaluated via repeated measures single case designs, in which assessments were administered twice before therapy, immediately post therapy and five weeks later. Outcome measures included Object Picture Naming (study 1), Sentence Elicitation Pictures (study 2), Naming 84 items from the Object and Action Naming Battery (study 2), Narrative Production (Study 2), the Northwestern Assessment of Verb and Sentences: Argument Structure Production Test (Study 2) and Communication Activities of Daily Living – 2 (Study 1 & 2). Outcomes & Results: Feasibility results were excellent. Both participants were fully compliant with the therapy regime. There was at least 90% fidelity with the treatment protocols and participant views were positive. Outcomes varied across the studies. The noun therapy significantly improved the naming of treated words, with good maintenance. Lexical gains were less evident on the Sentence Elicitation Pictures used in the VNeST study. Neither study demonstrated generalisation to untreated words, connected speech or functional communication. Conclusions: Two treatment approaches, designed for face to face delivery, could be delivered remotely in EVA Park. Outcomes for the noun treatment were comparable to previous evaluations. Comparisons with previous research were more challenging for VNeST, owing to differences in methodology. Further evaluations of other treatment approaches are warranted

Malignant pleural mesothelioma:An update on investigation, diagnosis and treatment

Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised

Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains.

BACKGROUND: Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series. METHODS: We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic variants were assessed using the American College of Medical Genetics criteria for pathogenicity. Individuals with two or more variants within a relevant disease gene panel were defined as 'oligogenic'. RESULTS: The majority of oligogenic variant combinations consisted of a highly penetrant allele or known risk factor in combination with another rare but likely benign allele. The presence of oligogenic variants did not influence the age of onset or disease severity. After controlling for the single known major risk allele, the frequency of oligogenic variants was no different between cases and controls. CONCLUSIONS: A priori, individuals with AD, PD-DLB and FTD-ALS are more likely to harbour a known genetic risk factor, and it is the burden of these variants in combination with rare benign alleles that is likely to be responsible for some oligogenic associations. Controlling for this bias is essential in studies investigating a potential role for oligogenic variation in neurodegenerative diseases

LA CASA DEL TURISMO EN SANTA CATALINA [Material gráfico]

FOTO PSOTAL DE PUERTO DE LA LUZ, CASA TURISMOCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Human hypoxic pulmonary vasoconstriction is unaltered by 8 h of preceding isocapnic hyperoxia

Exposure to sustained hypoxia of 8 h duration increases the sensitivity of the pulmonary vasculature to acute hypoxia, but it is not known whether exposure to sustained hyperoxia affects human pulmonary vascular control. We hypothesized that exposure to 8 h of hyperoxia would diminish the hypoxic pulmonary vasoconstriction (HPV) that occurs in response to a brief exposure to hypoxia. Eleven healthy volunteers were studied in a crossover protocol with randomization of order. Each volunteer was exposed to acute isocapnic hypoxia (end-tidal PO2 = 50 mmHg for 10 min) before and after 8 h of hyperoxia (end-tidal PO2 = 420 mmHg) or euoxia (end-tidal PO2 = 100 mmHg). After at least three days, each volunteer returned and was exposed to the other condition. Systolic pulmonary artery pressure (an index of HPV) and cardiac output were measured using Doppler echocardiography. Eight hours of hyperoxia had no effect on HPV or the response of cardiac output to acute hypoxia

Characteristics and pathways of long-stay patients in high and medium secure settings in England : a secondary publication from a large mixed-methods study

Background: Many patients experience extended stays within forensic care, but the characteristics of long-stay patients are poorly understood. Aims: To describe the characteristics of long-stay patients in high and medium secure settings in England. Method: Detailed file reviews provided clinical, offending and risk data for a large representative sample of 401 forensic patients from 2 of the 3 high secure settings and from 23 of the 57 medium secure settings in England on 1 April 2013. The threshold for long-stay status was defined as 5 years in medium secure care or 10 years in high secure care, or 15 years in a combination of high and medium secure settings. Results: 22% of patients in high security and 18% in medium security met the definition for ‘long-stay’, with 20% staying longer than 20 years. Of the long-stay sample, 58% were violent offenders (22% both sexual and violent), 27% had been convicted for violent or sexual offences whilst in an institutional setting, and 26% had committed a serious assault on staff in the last 5 years. The most prevalent diagnosis was schizophrenia (60%) followed by personality disorder (47%, predominantly antisocial and borderline types); 16% were categorised as having an intellectual disability. Overall, 7% of the long-stay sample had never been convicted of any offence, and 16.5% had no index offence prompting admission. Although some significant differences were found between the high and medium secure samples, there were more similarities than contrasts between these two levels of security. The treatment pathways of these long-stay patients involved multiple moves between settings. An unsuccessful referral to a setting of lower security was recorded over the last 5 years for 33% of the sample. Conclusions: Long-stay patients accounted for one fifth of the forensic inpatient population in England in this representative sample. A significant proportion of this group remain unsettled. High levels of personality pathology and the risk of assaults on staff and others within the care setting are likely to impact on treatment and management. Further research into the treatment pathways of longer stay patients is warranted to understand the complex trajectories of this group