Since the earliest days of the Republic, both legal scholars and titans of industry have had to grapple with the often competing priorities of federal power versus the hodgepodge of state regulators, ...both of which demand exacting adherence to often highly technical requirements. From Justice John Marshall striking down the State of Maryland's attempts to tax a federally chartered bank in McCullock v. Maryland, to Justice Antonin Scalia recognizing the State of New York's role of sovereign-as-law-enforcer in Cuomo v. Clearing House, the highest courts in the land have struggled to find a balance between upholding the powers of federal instrumentalities, and recognizing the legitimate police powers reserved to the states. In perhaps no other area of banking is this struggle for regulatory supremacy more apparent than in consumer lending, particularly residential mortgage lending. In this article, we explore the application of the evolving principles of federal preemption under the National Bank Act and regulations of the Office of the Comptroller of the Currency to state laws requiring mortgage loan servicers to provide certain notices following satisfaction of a mortgage on residential real estate. As the article discusses, while there may be notable arguments in favor of some role of the states in what would appear to be an area that is inherently local and intrastate in nature, i.e., the regulation of transfers of interests in land, in applying the delicate balance between federal and state authority, the more legally sound approach is that such attempts by states to regulate the federally granted loan servicing powers of federal instrumentalities, such as national banks, offends our traditional and widely accepted notions of preemption.
Background:
Limb strength is a central component of neurological assessment and monitoring in nursing practice, yet there is a lack of research examining the tools used by nurses or challenges nurses ...encounter when using these tools. The evidence base is lacking to inform effective practice and the underpinning educational approaches.
Aim:
To determine which tools are used by UK and Irish neuroscience nurses in the assessment of limb strength and the associated challenges and variations in practice.
Methods:
This study used an online self-reported survey design to ascertain which tools neuroscience nurses used and their experience of using these (n=160).
Findings:
Practices varied, with a dominance of two tools being used in practice: the Medical Research Council scale and the ‘normal power’ to ‘no movement’ scale found on the neurological observation chart. Most respondents used the same tool across all conditions.
Conclusion:
This study highlights variations in assessment practice and the absence of a sound evidence base behind choice of motor limb strength assessment tools used.
The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in impacting on human health remain ...poorly understood. We performed longitudinal metagenomic analysis of fecal viruses in healthy adults that reveal high temporal stability, individual specificity, and correlation with the bacterial microbiome. Using a database-independent approach that uses most of the sequencing data, we uncovered the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of viral genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella, and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.
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•The human gut virome is highly individual and stable for up to 1 year•A stable and predominant fraction of viruses constitutes a persistent personal virome•Persistent bacteriophages can be linked to highly predominant gut bacterial taxa•Virulent crAss-like and Microviridae bacteriophages predominate and persist in the gut
Shkoporov et al. demonstrate high individual specificity and temporal stability of the human gut virome. They describe a numerically prevalent and persisting fraction of the viral community, termed persistent personal virome (PPV). The PPV consists mainly of virulent bacteriophages predicted to target major taxonomic groups of gut bacteria.
Recent studies have demonstrated that the human gut is populated by complex, highly individual and stable communities of viruses, the majority of which are bacteriophages. While disease-specific ...alterations in the gut phageome have been observed in IBD, AIDS and acute malnutrition, the human gut phageome remains poorly characterised. One important obstacle in metagenomic studies of the human gut phageome is a high level of discrepancy between results obtained by different research groups. This is often due to the use of different protocols for enriching virus-like particles, nucleic acid purification and sequencing. The goal of the present study is to develop a relatively simple, reproducible and cost-efficient protocol for the extraction of viral nucleic acids from human faecal samples, suitable for high-throughput studies. We also analyse the effect of certain potential confounding factors, such as storage conditions, repeated freeze-thaw cycles, and operator bias on the resultant phageome profile. Additionally, spiking of faecal samples with an exogenous phage standard was employed to quantitatively analyse phageomes following metagenomic sequencing. Comparative analysis of phageome profiles to bacteriome profiles was also performed following 16S rRNA amplicon sequencing.
Faecal phageome profiles exhibit an overall greater individual specificity when compared to bacteriome profiles. The phageome and bacteriome both exhibited moderate change when stored at + 4 °C or room temperature. Phageome profiles were less impacted by multiple freeze-thaw cycles than bacteriome profiles, but there was a greater chance for operator effect in phageome processing. The successful spiking of faecal samples with exogenous bacteriophage demonstrated large variations in the total viral load between individual samples.
The faecal phageome sequencing protocol developed in this study provides a valuable additional view of the human gut microbiota that is complementary to 16S amplicon sequencing and/or metagenomic sequencing of total faecal DNA. The protocol was optimised for several confounding factors that are encountered while processing faecal samples, to reduce discrepancies observed within and between research groups studying the human gut phageome. Rapid storage, limited freeze-thaw cycling and spiking of faecal samples with an exogenous phage standard are recommended for optimum results.
In this section of the European Resuscitation Council Guidelines 2021, key information on the epidemiology and outcome of in and out of hospital cardiac arrest are presented. Key contributions from ...the European Registry of Cardiac Arrest (EuReCa) collaboration are highlighted. Recommendations are presented to enable health systems to develop registries as a platform for quality improvement and to inform health system planning and responses to cardiac arrest.
Surgery for epilepsy West, Siobhan; Nolan, Sarah J; Cotton, Jennifer ...
Cochrane database of systematic reviews,
07/2015
7
Journal Article
Peer reviewed
Focal epilepsies are caused by a malfunction of nerve cells localised in one part of one cerebral hemisphere. In studies, estimates of the number of individuals with focal epilepsy who do not become ...seizure-free despite optimal drug therapy vary according to the age of the participants and which focal epilepsies are included, but have been reported as at least 20% and in some studies up to 70%. If the epileptogenic zone can be located surgical resection offers the chance of a cure with a corresponding increase in quality of life.
The primary objective is to assess the overall outcome of epilepsy surgery according to evidence from randomised controlled trials.The secondary objectives are to assess the overall outcome of epilepsy surgery according to non-randomised evidence and to identify the factors that correlate to remission of seizures postoperatively.
We searched the Cochrane Epilepsy Group Specialised Register (June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 6), MEDLINE (Ovid) (2001 to 4 July 2013), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for relevant trials up to 4 July 2013.
Eligible studies were randomised controlled trials (RCTs), cohort studies or case series, with either a prospective and/or retrospective design, including at least 30 participants, a well-defined population (age, sex, seizure type/frequency, duration of epilepsy, aetiology, magnetic resonance imaging (MRI) diagnosis, surgical findings), an MRI performed in at least 90% of cases and an expected duration of follow-up of at least one year, and reporting an outcome relating to postoperative seizure control.
Three groups of two review authors independently screened all references for eligibility, assessed study quality and risk of bias, and extracted data. Outcomes were proportion of participants achieving a good outcome according to the presence or absence of each prognostic factor of interest. We intended to combine data with risk ratios (RR) and 95% confidence intervals.
We identified 177 studies (16,253 participants) investigating the outcome of surgery for epilepsy. Four studies were RCTs (including one that randomised participants to surgery or medical treatment). The risk of bias in the RCTs was unclear or high, limiting our confidence in the evidence that addressed the primary review objective. Most of the remaining 173 non-randomised studies had a retrospective design; they were of variable size, were conducted in a range of countries, recruited a wide demographic range of participants, used a wide range of surgical techniques and used different scales used to measure outcomes. We performed quality assessment using the Effective Public Health Practice Project (EPHPP) tool and determined that most studies provided moderate or weak evidence. For 29 studies reporting multivariate analyses we used the Quality in Prognostic Studies (QUIPS) tool and determined that very few studies were at low risk of bias across the domains.In terms of freedom from seizures, one RCT found surgery to be superior to medical treatment, two RCTs found no statistically significant difference between anterior temporal lobectomy (ATL) with or without corpus callosotomy or between 2.5 cm or 3.5 cm ATL resection, and one RCT found total hippocampectomy to be superior to partial hippocampectomy. We judged the evidence from the four RCTs to be of moderate to very low quality due to the lack of information reported about the randomised trial design and the restricted study populations.Of the 16,253 participants included in this review, 10,518 (65%) achieved a good outcome from surgery; this ranged across studies from 13.5% to 92.5%. Overall, we found the quality of data in relation to the recording of adverse events to be very poor.In total, 118 studies examined between one and eight prognostic factors in univariate analysis. We found the following prognostic factors to be associated with a better post-surgical seizure outcome: an abnormal pre-operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre-operative MRI and electroencephalography (EEG), history of febrile seizures, absence of focal cortical dysplasia/malformation of cortical development, presence of tumour, right-sided resection and presence of unilateral interictal spikes. We found no evidence that history of head injury, presence of encephalomalacia, presence of vascular malformation or presence of postoperative discharges were prognostic factors of outcome. We observed variability between studies for many of our analyses, likely due to the small study sizes with unbalanced group sizes, variation in the definition of seizure outcome, definition of the prognostic factor and the influence of the site of surgery, all of which we observed to be related to postoperative seizure outcome. Twenty-nine studies reported multivariable models of prognostic factors and the direction of association of factors with outcome was generally the same as found in the univariate analyses. However, due to the different multivariable analysis approaches and selective reporting of results, meaningful comparison of multivariate analysis with univariate meta-analysis is difficult.
The study design issues and limited information presented in the included studies mean that our results provide limited evidence to aid patient selection for surgery and prediction of likely surgical outcome. Future research should be of high quality, have a prospective design, be appropriately powered and focus on specific issues related to diagnostic tools, the site-specific surgical approach and other issues such as the extent of resection. Prognostic factors related to the outcome of surgery should be investigated via multivariable statistical regression modelling, where variables are selected for modelling according to clinical relevance and all numerical results of the prognostic models are fully reported. Protocols should include pre- and postoperative measures of speech and language function, cognition and social functioning along with a mental state assessment. Journal editors should not accept papers where adverse events from a medical intervention are not recorded. Improvements in the development of cancer care over the past three to four decades have been achieved by answering well-defined questions through the conduct of focused RCTs in a step-wise fashion. The same approach to surgery for epilepsy is required.
This seminar discusses the history and development of techniques for surgical intervention for people with refractory focal epilepsy. Published surgical success rates and prognostic factors ...associated with post‐operative seizure freedom from individual studies have been variable and contradictory. We present here the key findings of a Cochrane systematic review of all evidence published since the introduction of magnetic resonance imaging (MRI) to pre‐operative surgical assessment in 1984. Our findings show the usefulness of uncontrolled case series is now past. Future studies with a prospective controlled design should focus on specific research questions to help improve results and provide better‐informed advice.
Breast cancer brain metastases (BrMs) are defined by complex adaptations to both adjuvant treatment regimens and the brain microenvironment. Consequences of these alterations remain poorly ...understood, as does their potential for clinical targeting. We utilized genome-wide molecular profiling to identify therapeutic targets acquired in metastatic disease.
Gene expression profiling of 21 patient-matched primary breast tumors and their associated brain metastases was performed by TrueSeq RNA-sequencing to determine clinically actionable BrM target genes. Identified targets were functionally validated using small molecule inhibitors in a cohort of resected BrM ex vivo explants (n = 4) and in a patient-derived xenograft (PDX) model of BrM. All statistical tests were two-sided.
Considerable shifts in breast cancer cell-specific gene expression profiles were observed (1314 genes upregulated in BrM; 1702 genes downregulated in BrM; DESeq; fold change > 1.5, Padj < .05). Subsequent bioinformatic analysis for readily druggable targets revealed recurrent gains in RET expression and human epidermal growth factor receptor 2 (HER2) signaling. Small molecule inhibition of RET and HER2 in ex vivo patient BrM models (n = 4) resulted in statistically significantly reduced proliferation (P < .001 in four of four models). Furthermore, RET and HER2 inhibition in a PDX model of BrM led to a statistically significant antitumor response vs control (n = 4, % tumor growth inhibition mean difference; SD, anti-RET = 86.3% 1176; 258.3, P < .001; anti-HER2 = 91.2% 1114; 257.9, P < .01).
RNA-seq profiling of longitudinally collected specimens uncovered recurrent gene expression acquisitions in metastatic tumors, distinct from matched primary tumors. Critically, we identify aberrations in key oncogenic pathways and provide functional evidence for their suitability as therapeutic targets. Altogether, this study establishes recurrent, acquired vulnerabilities in BrM that warrant immediate clinical investigation and suggests paired specimen expression profiling as a compelling and underutilized strategy to identify targetable dependencies in advanced cancers.
Nursing in an age of multimorbidity O'Connor, Siobhan; Deaton, Christi; Nolan, Fiona ...
BMC nursing,
11/2018, Volume:
17, Issue:
1
Journal Article
Peer reviewed
Open access
A changing sociodemographic landscape has seen rising numbers of people with two or more long-term health conditions. Multimorbidity presents numerous challenges for patients and families and those ...who work in healthcare services. Therefore, the nursing profession needs to understand the issues involved in supporting people with multiple chronic conditions and how to prepare the future workforce to care for them.
A descriptive, exploratory study was used to examine the future of nursing in an age of multimorbidity. An hour-long Twitter chat was organised and run by the Florence Nightingale Foundation Chairs of Clinical Nursing Practice Research to discuss this important area of practice and identify what needs to be done to adequately upskill and prepare the nursing profession to care for individuals with more than one long-term illness. Questions were formulated in advance to provide some structure to the online discussion. Data were collected and analysed from the social media platform using NVivo and an analytics tool called Keyhole. Descriptive statistics were used to describe participants and thematic analysis aided the identification of key themes.
Twenty-four people, from a range of nursing backgrounds and organisations, took part in the social media discussion. Five themes encompassing coping with treatment burden, delivering holistic care, developing an evidence base, stimulating learning and redesigning health services were seen as key to ensuring nurses could care for people with multimorbidity and prevent others from developing chronic health conditions.
Multimorbidity is a pressing health issue in today's society. Changes in nursing research, education and practice are required to help the profession work collaboratively with patients, families and multidisciplinary teams to better manage and prevent chronic illness now and in the future.
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