A Raid on the Inarticulate: The Problem of Language in the Poetry of W.S. Merwin

In this paper, I hope to examine Merwin\u27s ultimately successful quest for such a language and such a myth. Beginning with a brief description of his early work, in which the problem of language becomes a seemingly insuperable barrier to an understanding of the world, I wish to demonstrate his gradual evolution of a poetic voice which is both contemporary and universal. Of course, a study of this length will inevitably be marred by a certain amount of over-generalization and simplification. Merwin\u27s struggle with language has been a long and arduous one, and he has explored many byways on the journey which we will simply not be able to investigate. However, I trust that this summary of the major stages of Merwin\u27s poetic development, with a special concentration on the poems which mark its fruition, will provide a cogent introduction to his response to the unique poetic problems of his time, as well as offer some insights as to the achievement of his work

A Raid on the Inarticulate: The Problem of Language in the Poetry of W.S. Merwin

In this paper, I hope to examine Merwin\u27s ultimately successful quest for such a language and such a myth. Beginning with a brief description of his early work, in which the problem of language becomes a seemingly insuperable barrier to an understanding of the world, I wish to demonstrate his gradual evolution of a poetic voice which is both contemporary and universal. Of course, a study of this length will inevitably be marred by a certain amount of over-generalization and simplification. Merwin\u27s struggle with language has been a long and arduous one, and he has explored many byways on the journey which we will simply not be able to investigate. However, I trust that this summary of the major stages of Merwin\u27s poetic development, with a special concentration on the poems which mark its fruition, will provide a cogent introduction to his response to the unique poetic problems of his time, as well as offer some insights as to the achievement of his work

Examining variations in prescribing safety in UK general practice: cross sectional study using the Clinical Practice Research Datalink

Study question: What is the prevalence of different types of potentially hazardous prescribing in general practice in the United Kingdom, and what is the variation between practices? Methods: A cross sectional study included all adult patients potentially at risk of a prescribing or monitoring error defined by a combination of diagnoses and prescriptions in 526 general practices contributing to the Clinical Practice Research Datalink (CPRD) up to 1 April 2013. Primary outcomes were the prevalence of potentially hazardous prescriptions of anticoagulants, anti-platelets, NSAIDs, β blockers, glitazones, metformin, digoxin, antipsychotics, combined hormonal contraceptives, and oestrogens and monitoring by blood test less frequently than recommended for patients with repeated prescriptions of angiotensin converting enzyme inhibitors and loop diuretics, amiodarone, methotrexate, lithium, or warfarin. Study answer and limitations: 49 927 of 949 552 patients at risk triggered at least one prescribing indicator (5.26%, 95% confidence interval 5.21% to 5.30%) and 21 501 of 182 721 (11.8%, 11.6% to 11.9%) triggered at least one monitoring indicator. The prevalence of different types of potentially hazardous prescribing ranged from almost zero to 10.2%, and for inadequate monitoring ranged from 10.4% to 41.9%. Older patients and those prescribed multiple repeat medications had significantly higher risks of triggering a prescribing indicator whereas younger patients with fewer repeat prescriptions had significantly higher risk of triggering a monitoring indicator. There was high variation between practices for some indicators. Though prescribing safety indicators describe prescribing patterns that can increase the risk of harm to the patient and should generally be avoided, there will always be exceptions where the indicator is clinically justified. Furthermore there is the possibility that some information is not captured by CPRD for some practices—for example, INR results in patients receiving warfarin. What this study adds: The high prevalence for certain indicators emphasises existing prescribing risks and the need for their appropriate consideration within primary care, particularly for older patients and those taking multiple medications. The high variation between practices indicates potential for improvement through targeted practice level intervention. Funding, competing interests, data sharing: National Institute for Health Research through the Greater Manchester Primary Care Patient Safety Translational Research Centre (grant No GMPSTRC-2012-1). Data from CPRD cannot be shared because of licensing restrictions

Antipsychotic prescribing to patients diagnosed with dementia without a diagnosis of psychosis in the context of national guidance and drug safety warnings: longitudinal study in UK general practice

Introduction: Policy interventions to address inappropriate prescribing of antipsychotic drugs to older people diagnosed with dementia are commonplace. In the UK, warnings were issued by the Medicines Healthcare products Regulatory Agency in 2004, 2009 and 2012 and the National Institute for Health and Care Excellence guidance was published in 2006. It is important to evaluate the impact of such interventions. Methods: We analysed routinely collected primary-care data from 111,346 patients attending one of 689 general practices contributing to the Clinical Practice Research Datalink to describe the temporal changes in the prescribing of antipsychotic drugs to patients aged 65 years or over diagnosed with dementia without a concomitant psychosis diagnosis from 2001 to 2014 using an interrupted time series and a before-and-after design. Logistic regression methods were used to quantify the impact of patient and practice level variables on prescribing prevalence. Results: Prescribing of first-generation antipsychotic drugs reduced from 8.9% in 2001 to 1.4% in 2014 (prevalence ratio 2014/2001 adjusted for age, sex and clustering within practices (0.14, 95% confidence interval 0.12–0.16), whereas there was little change for second-generation antipsychotic drugs (1.01, confidence interval 0.94–1.17). Between 2004 and 2012, several policy interventions coincided with a pattern of ups and downs, whereas the 2006 National Institute for Health and Care Excellence guidance was followed by a gradual longer term reduction. Since 2013, the decreasing trend in second-generation antipsychotic drug prescribing has plateaued largely driven by the increasing prescribing of risperidone. Conclusions: Increased surveillance and evaluation of drug safety warnings and guidance are needed to improve the impact of future interventions

Primary care medication safety surveillance with integrated primary and secondary care electronic health records: a cross-sectional study

Introduction: The extent of preventable medication-related hospital admissions and medication-related issues in primary care is significant enough to justify developing decision support systems for medication safety surveillance. The prerequisite for such systems is defining a relevant set of medication safety-related indicators and understanding the influence of both patient and general practice characteristics on medication prescribing and monitoring. Objective: The aim of the study was to investigate the feasibility of linked primary and secondary care electronic health record data for surveillance of medication safety, examining not only prescribing but also monitoring, and associations with patient- and general practice-level characteristics. Methods: A cross-sectional study was conducted using linked records of patients served by one hospital and over 50 general practices in Salford, UK. Statistical analysis consisted of mixed-effects logistic models, relating prescribing safety indicators to potential determinants. Results: The overall prevalence (proportion of patients with at least one medication safety hazard) was 5.45 % for prescribing indicators and 7.65 % for monitoring indicators. Older patients and those on multiple medications were at higher risk of prescribing hazards, but at lower risk of missed monitoring. The odds of missed monitoring among all patients were 25 % less for males, 50 % less for patients in practices that provide general practitioner training, and threefold higher in practices serving the most deprived compared with the least deprived areas. Practices with more prescribing hazards did not tend to show more monitoring issues. Conclusions:Systematic collection, collation, and analysis of linked primary and secondary care records produce plausible and useful information about medication safety for a health system. Medication safety surveillance systems should pay close attention to patient age and polypharmacy with respect to both prescribing and monitoring failures; treat prescribing and monitoring as different statistical processes, rather than a combined measure of prescribing safety; and audit the socio-economic equity of missed monitoring

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.Peer reviewe

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy