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A series of eleven patients prescribed intramuscular clozapine at five UK sites is presented. Using routinely collected clinical data, we describe the use, efficacy and safety of this treatment modality.
We administered 188 doses of intramuscular clozapine to eight patients. The remaining three patients accepted oral medication. With the exception of minor injection site pain and nodules, side-effects were as expected with oral clozapine, and there were no serious untoward events. Nine patients were successfully established on oral clozapine with significant improvement in their clinical presentations.
Although a novel formulation in the UK, we have shown that intramuscular clozapine can be used safely and effectively when the oral route is initially refused.
Objectives: Essential tremor (ET) confers an increased risk for developing both amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal measures for detecting mild cognitive changes in individuals with this movement disorder have not been established. We sought to identify the cognitive domains and specific motor-free neuropsychological tests that are most sensitive to mild deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5, which is generally associated with a clinical diagnosis of MCI. Methods: A total of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological study underwent an extensive motor-free neuropsychological test battery and were assigned a CDR score. Logistic regression analyses were performed to identify the neuropsychological tests which best identified individuals with CDR of 0.5 (mild deficits in cognition) versus 0 (normal cognition). Results: In regression models, we identified five tests in the domains of Memory and Executive Function which best discriminated subjects with CDR of 0.5 versus 0 (86.9% model classification accuracy). These tests were the California Verbal Learning Test II Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching Fluency, and Color-Word Inhibition. Conclusions: Mild cognitive difficulty among ET subjects is best predicted by combined performance on five measures of memory and executive function. These results inform the nature of cognitive dysfunction in ET and the creation of a brief cognitive battery to assess patients with ET for cognitively driven dysfunction in life that could indicate the presence of MCI. (JINS, 2018, 24, 1084–1098)
In recent years, those involved in regulating, forming or advising faith communities have had much to contend with: the expansion of the vicarious liability doctrine, the status of ministers of religion and the decision in Shergill v Khaira, not to mention the General Data Protection Regulation. These issues share a common denominator: they require faith communities to give close consideration to the values which they seek to articulate and foster in the expression of their own autonomy and right of self-determination. That is, they serve as a prompt to reconnect with the intellectus and vinculo iuris of their own ecclesial norms. This article is intended to encourage such an exercise and to contribute to a discussion of the potential points of collaboration between the civil law and faith communities in securing dispute resolution by which ecclesial values may be accommodated.
Individuals with essential tremor (ET) exhibit a range of cognitive deficits generally conceptualized as “dysexecutive” or “fronto-subcortical,” and thought to reflect disrupted cortico-cerebellar networks. In light of emerging evidence that ET increases risk for Alzheimer’s disease (AD), it is critical to more closely examine the nature of specific cognitive deficits in ET, with particular attention to amnestic deficits that may signal early AD.
We performed a cross-sectional analysis of baseline data from 128 ET cases (age 80.4±9.5 years) enrolled in a longitudinal, clinical-pathological study. Cases underwent a comprehensive battery of motor-free neuropsychological tests and a functional assessment to inform clinical diagnoses of normal cognition (ET-NC), mild cognitive impairment (MCI) (ET-MCI), or dementia (ET-D). ET-MCI was subdivided into subtypes including: amnestic single-domain (a-MCI), amnestic multi-domain (a-MCI+), non-amnestic single-domain (na-MCI), or non-amnestic multi-domain (na-MCI+).
Ninety-one (71.1%) cases were ET-NC, 24 (18.8%) were ET-MCI, and 13 (10.2%) were ET-D. Within MCI, the a-MCI+ subtype was the most common (13/24; 54.2%) followed by a-MCI (4/24; 16.7%), na-MCI+ (4/24; 16.7%), and na-MCI (3/24; 12.5%). Cases with amnestic MCI demonstrated lower recognition memory Z-scores (−2.4±1.7) than non-amnestic groups (−0.9±1.2) (p=.042).
Amnestic MCI, defined by impaired memory recall but associated with lower memory storage scores, was the most frequent MCI subtype in our study. Such impairment has not been explicitly discussed in the context of ET and may be an early hallmark of AD. Results have implications for the prognosis of specific cognitive deficits in ET. (JINS, 2017, 23, 390–399)
Apart from their effector functions in allergic disorders, tissue-resident mast cells (MC) are gaining recognition as initiators of inflammatory events through their distinctive ability to secrete many bioactive molecules harbored in cytoplasmic granules. Activation triggers mediator release through a regulated exocytosis named degranulation. MC activation is still substantiated by measuring systemic levels of MC-restricted mediators. However, identifying the anatomical location of MC activation is valuable for disease diagnosis. We designed a computer-assisted morphometric method based on image analysis of methylene blue (MB)-stained normal mouse skin tissue sections that quantitates actual in situ MC activation status. We reasoned MC cytoplasm could be viewed as an object featuring unique relative mass values based on activation status. Integrated optical density and area (A) ratios were significantly different between intact and degranulated MC (p<0.001). The examination of fractal characteristics is of translational diagnostic/prognostic value in cancer and readily applied to quantify cytoskeleton morphology and vasculature. Fractal dimension (D), a measure of their comparative space filling capacity and structural density, also differed significantly between intact and degranulated MC (p<0.001). Morphometric analysis provides a reliable and reproducible method for in situ quantification of MC activation status.
To design better antimicrobial stewardship programs, detailed data on the primary drivers and patterns of antibiotic use are needed.
To characterize the indications for antibiotic therapy, agents used, duration, combinations, and microbiological justification in 6 acute-care US facilities with varied location, size, and type of antimicrobial stewardship programs.
DESIGN, PARTICIPANTS, AND SETTING
Retrospective medical chart review was performed on a random cross-sectional sample of 1,200 adult inpatients, hospitalized (>24 hrs) in 6 hospitals, and receiving at least 1 antibiotic dose on 4 index dates chosen at equal intervals through a 1-year study period (October 1, 2009–September 30, 2010).
Infectious disease specialists recorded patient demographic characteristics, comorbidities, microbiological and radiological testing, and agents used, dose, duration, and indication for antibiotic prescriptions.
On the index dates 4,119 (60.5%) of 6,812 inpatients were receiving antibiotics. The random sample of 1,200 case patients was receiving 2,527 antibiotics (average: 2.1 per patient); 540 (21.4%) were prophylactic and 1,987 (78.6%) were therapeutic, of which 372 (18.7%) were pathogen-directed at start. Of the 1,615 empirical starts, 382 (23.7%) were subsequently pathogen-directed and 1,231 (76.2%) remained empirical. Use was primarily for respiratory (27.6% of prescriptions) followed by gastrointestinal (13.1%) infections. Fluoroquinolones, vancomycin, and antipseudomonal penicillins together accounted for 47.1% of therapy-days.
Use of broad-spectrum empirical therapy was prevalent in 6 US acute care facilities and in most instances was not subsequently pathogen directed. Fluoroquinolones, vancomycin, and antipseudomonal penicillins were the most frequently used antibiotics, particularly for respiratory indications.
We present the results of an approximately 6 100 deg2 104–196 MHz radio sky survey performed with the Murchison Widefield Array during instrument commissioning between 2012 September and 2012 December: the MWACS. The data were taken as meridian drift scans with two different 32-antenna sub-arrays that were available during the commissioning period. The survey covers approximately 20.5 h < RA < 8.5 h, − 58° < Dec < −14°over three frequency bands centred on 119, 150 and 180 MHz, with image resolutions of 6–3 arcmin. The catalogue has 3 arcmin angular resolution and a typical noise level of 40 mJy beam− 1, with reduced sensitivity near the field boundaries and bright sources. We describe the data reduction strategy, based upon mosaicked snapshots, flux density calibration, and source-finding method. We present a catalogue of flux density and spectral index measurements for 14 110 sources, extracted from the mosaic, 1 247 of which are sub-components of complexes of sources.
During its 2012 session the Florida Legislature amended the text of the Florida Statutes which lists exemptions from the requirements of obtaining a Florida drivers’ license. Removed from the text of Florida Statute 322.04 was the line concerning nonresidents, both fellow Americans and international visitors, “who has in his or her immediate possession a valid noncommercial driver's license issued to the nonresident in his or her home state or country [emphasis added].” Inserted was a new line, “An International Driving Permit issued in his or her name in his or her country of residence and a valid license issued in that country.” International visitors were required to have in their possession not only a valid drivers’ license, but also an International Driving Permit (IDP) that translated into English the personal identification information of the driver. The change took effect January 1, 2013, but even before that date, Florida faced allegations that it was violating international law with this new requirement.
Significant new opportunities for astrophysics and cosmology have been identified at low radio frequencies. The Murchison Widefield Array is the first telescope in the southern hemisphere designed specifically to explore the low-frequency astronomical sky between 80 and 300 MHz with arcminute angular resolution and high survey efficiency. The telescope will enable new advances along four key science themes, including searching for redshifted 21-cm emission from the EoR in the early Universe; Galactic and extragalactic all-sky southern hemisphere surveys; time-domain astrophysics; and solar, heliospheric, and ionospheric science and space weather. The Murchison Widefield Array is located in Western Australia at the site of the planned Square Kilometre Array (SKA) low-band telescope and is the only low-frequency SKA precursor facility. In this paper, we review the performance properties of the Murchison Widefield Array and describe its primary scientific objectives.
Since the 1990s, the concept of ‘state-building’ has become the means by which intervenors have attempted to tackle ‘state failure/fragility’. The ‘ideal’ referred to when attempting to do this – both theoretically and in practice – has been that of the classic ‘nation-state’ as developed by Max Weber. To answer the question posed by the title above, the article first looks generally at the evolution of the current state-building paradigm and global governance discourse. Second, a background of historical attempts at state-building in Afghanistan is given. Third, an assessment is made of the international community's approach to Afghanistan since 2001. Finally, the appropriateness of replicating a Weberian state-building model onto more traditional societies such as Afghanistan – where modes of governance and authority are often informal, complex, and characterized by historical and charismatic sources of legitimacy – is addressed. Until now, such contexts have barely been acknowledged, still less understood, by intervenors. Today, however, some academics are beginning to outline an alternative response to state fragility, recognizing more traditional sources of legitimacy and a hybridity of political order.