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Appropriateness of transmission-based precautions after positive result for a non-SARS-CoV-2 virus was evaluated. Most patients (77.2%) lacked appropriate precautions within 3 hours of virus detection; 36.9% remained without appropriate precautions during their stay. With recent cessation of universal masking, adherence to infection control best practices is needed to optimize safety.
Compare outcomes of patients receiving high-dose oral beta-lactam versus standard oral therapy for Enterobacterales bacteremia from a urinary tract infection (UTI).
Design:
Retrospective, multicenter, observational cohort.
Setting:
Three Michigan community teaching hospitals.
Patients:
Adult patients admitted between February 1, 2020, and October 1, 2022, with gram-negative bacteremia from a urinary source were evaluated. Patients receiving active empiric intravenous (IV) antibiotics and transitioned to appropriately dosed oral cephalexin, amoxicillin, fluoroquinolone (FQ), or trimethoprim/sulfamethoxazole (TMP/SMX) were included. Patients receiving less than 72 hours of oral therapy, diagnosed with renal abscess, lobar nephronia, or expired during admission were excluded.
Methods:
Standard oral therapy was defined as FQ or TMP/SMX. The primary outcome compared the composite of recurrent bacteremia or mortality within 30 days of therapy between groups. Secondary outcomes compared recurrent UTI, emergency department or hospital readmission, and Clostridioides difficile within 30 days.
Results:
194 patients were included (beta-lactam, n = 75 vs standard therapy, n =119). Patients in both groups were treated for a median of 11 days, with 4 days IV and 7 days oral therapy. There was no difference in the primary outcome between groups (beta-lactam 1.3% vs standard therapy 1.7%, OR 1.27 [95% CI 0.11–14.2]). No patients experienced C. difficile in either group (p = 1.0). Infectious disease consultation was independently associated with standard therapy prescribing (OR 4.4 [95% CI 2.24–8.26]).
Conclusion:
High-dose oral beta-lactams were as safe and effective as oral FQ or TMP/SMX for the treatment of bacteremia from a urinary source. Most patients received 8–10 days of therapy in both groups.
We have demonstrated the effect of covering an N95 filtering facepiece respirator (FFR) with an overlying face mask. In total, 100 participants successfully completed quantitative fit testing wearing a 3M 1870+ FFR. Among them, 13 (13%; 95% CI, 7%–22%) failed subsequent fit testing when simultaneously wearing a Halyard 47117 procedural mask over the FFR.
MeerTime is a five-year Large Survey Project to time pulsars with MeerKAT, the 64-dish South African precursor to the Square Kilometre Array. The science goals for the programme include timing millisecond pulsar (MSPs) to high precision (
${<} 1 \unicode{x03BC} \mathrm{s}$
) to study the Galactic MSP population and to contribute to global efforts to detect nanohertz gravitational waves with the International Pulsar Timing Array (IPTA). In order to plan for the remainder of the programme and to use the allocated time most efficiently, we have conducted an initial census with the MeerKAT ‘L-band’ receiver of 189 MSPs visible to MeerKAT and here present their dispersion measures, polarisation profiles, polarisation fractions, rotation measures, flux density measurements, spectral indices, and timing potential. As all of these observations are taken with the same instrument (which uses coherent dedispersion, interferometric polarisation calibration techniques, and a uniform flux scale), they present an excellent resource for population studies. We used wideband pulse portraits as timing standards for each MSP and demonstrated that the MeerTime Pulsar Timing Array (MPTA) can already contribute significantly to the IPTA as it currently achieves better than
$1\,\unicode{x03BC}\mathrm{s}$
timing accuracy on 89 MSPs (observed with fortnightly cadence). By the conclusion of the initial five-year MeerTime programme in 2024 July, the MPTA will be extremely significant in global efforts to detect the gravitational wave background with a contribution to the detection statistic comparable to other long-standing timing programmes.
We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain (
${\sim}2.8\,\mbox{K Jy}^{-1}$
) low-system temperature (
${\sim}18\,\mbox{K at }20\,\mbox{cm}$
) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar
$\mbox{J}0737{-}3039\mbox{A}$
, pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR
$\mbox{J}0540{-}6919$
, and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR
$\mbox{J}2241{-}5236$
exhibits a jitter limit of
$<4\,\mbox{ns h}^{-1}$
whilst timing of PSR
$\mbox{J}1909{-}3744$
over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.
This comparative study investigated consumption patterns, comorbidity and treatment utilization of opioid addicts in six European cities (Athens, Essen, London, Padua, Stockholm, Zurich).
Subjects and methods
Data were collected by structured face-to-face interviews. The representative sample comprises 599 addicts (100 patients per centre, 99 in London) at the start of a treatment episode.
Results
Patients were dependent on opioids for about 10 years. Regional differences were significant regarding the patients’ drug consumption pattern and their method of heroin administration (up to a fourth of the patients in Essen, London and Zurich usually smoke heroin). Concomitant use of benzodiazepines, cannabis and alcohol was common in all regions with the German and English samples showing the highest level of polydrug use. The prevalence of major depression was high in all regions (50%). Stockholm and London patients worry most about their physical health. Differences in the amount of needle sharing and especially in the use of public health service were prominent between the sites. Opioid addiction was a long-term disorder associated with a high burden of comorbidity and social problems in all cities.
Conclusion
The results of the study show significant interregional differences of opioid addicts which might require different treatment strategies in European countries to handle the problem.
An evolution of the low-frequency pulse profile of PSR B2217+47 is observed during a six-year observing campaign with the LOFAR telescope at 150 MHz. The evolution is manifested as a new component in the profile trailing the main peak. The leading part of the profile, including a newly-observed weak component, is steady during the campaign. The transient component is not visible in simultaneous observations at 1500 MHz using the Lovell telescope, implying a chromatic effect. A variation in the dispersion measure of the source is detected in the same timespan. Precession of the pulsar and changes in the magnetosphere are investigated to explain the profile evolution. However, the listed properties favour a model based on turbulence in the interstellar medium (ISM). This interpretation is confirmed by a strong correlation between the intensity of the transient component and main peak in single pulses. Since PSR B2217+47 is the fourth brightest pulsar visible to LOFAR, we speculate that ISM-induced pulse profile evolution might be relatively common but subtle and that SKA-Low will detect many similar examples. In this scenario, similar studies of pulse profile evolution could be used in parallel with scintillation arcs to characterize the properties of the ISM.
New finds of the trilobites Cobboldites tichkaensis Geyer, 1988, Pseudocobboldia pulchra (Hupé, 1953), Protolenus (Protolenus) densigranulatus Geyer, 1990, Latoucheia (Latoucheia) tichkaensis Hupé, 1953, and Acanthomicmacca neltneri Hupé, 1953, from the basal Middle Cambrian near the peak of Tizi n'Tichka in the central High Atlas, Morocco, supplement the known morphology of these species; the trilobites Acanthomicmacca new species, Oreisator tichkaensis new genus and species, and “Parasolenopleura” sp. from that locality are new. Acanthomicmacca neltneri is the first species of the genus and family that is described and figured in detail in terms of morphologic plasticity and ontogeny; Oreisator tichkaensis is the first ptychopariacean trilobite formally described and based on material from Africa. Trilobites and other fossils from the locality suggest a strong affinity to other Mediterranean and to Avalonian faunas, which is well supported by helcionelloid and hyolith genera.
Shelly fossils from the basal Middle Cambrian, near the peak of Tizi n'Tichka in the central High Atlas, Morocco, include the new hyolithids Oboedalites peregrinus new species, Emarites decorissimus new genus and species, Patholites insolitus new genus and species, Rodentilites cricetus new genus and species, Slapylites afer new species, Tajinella mosei new genus and species, and Tizilites creber new genus and species. New orthothecid hyoliths are Gracilitheca destombesi new species, Contitheca chrosniaki new species, Sysoievia exilis new genus and species and an indeterminate species of Circotheca. The presence of Obeodalites, Slapylites, and Contitheca suggests a strong affinity to other Mediterranean and to Avalonian faunas. Their occurrence in Morocco extends their geographic ranges from Europe, and further reenforces their usefulness as indicators of Middle Cambrian age.
The prevalence of culture-bound syndromes such as eating disorders in the countries of Central and Eastern Europe is unclear and comparative epidemiological studies are lacking. Before the political changes in 1989 we therefore investigated eating disorders, eating attitudes and psychological health in two Eastern European countries and in one Western democracy. A total of 1225 female and male medical students in Hungary, the German Democratic Republic (GDR) and Austria were surveyed. The instruments included the Eating Disorder Inventory and the GHQ. The prevalence of eating disorders was calculated on the basis of simulated DSM-III-R diagnosis. In females, bulimia nervosa prevalence rates of 0·6% (95% CI 0·02, 3·46), 1% (0·2, 2·95) and 0% (0, 2·07) were calculated for Austria, Hungary and the GDR, respectively. For subclinical bulimia nervosa, the rate for Hungary (3·8%; 1·95, 6·72) was twice as high as for Austria (1·9%; 0·39, 5·5) and the GDR (1·7%; 0·36, 4·88). Hungarian subjects indicated more psychiatric ‘caseness’ than their GDR or Austrian counterparts. We conclude that eating disorders represented at least as common a problem in Eastern as Western Europe before the changes in political organization. This may be due to an identification process with Western values. A further increase of eating disorders in these countries induced by the recent changes may be possible.
The presence of antigenic carbohydrate epitopes shared by Biomphalaria glabrata as well as by the sporocysts and miracidia representing snail-pathogenic larval stages of Schistosoma mansoni was assayed by immunohistochemical staining of paraformaldehyde-fixed tissues. To this end, both polyclonal rabbit antiserum raised against soluble egg antigens (SEA) of S. mansoni and monoclonal antibodies recognizing the carbohydrate epitopes LDN [GalNAc(β1-4)GlcNAc(β1-)], F-LDN [Fuc(α1-3)GalNAc(β1-4)GlcNAc(β1-)], LDN-F [GalNAc(β1-4)[Fuc(α1-3)]GlcNAc(β1-)], LDN-DF [GalNAc(β1-4)[Fuc(α1-2)Fuc(α1-3)]GlcNAc(β1-)] and Lewis X [Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-)] were used. Intriguingly, anti-SEA serum as well as anti-F-LDN antibodies displayed significant binding in the foot region, anterior tissue and the hepatopancreas of uninfected snails, whereas the Lewis X epitope was only weakly detectable in the latter tissue. In contrast, increased binding of antibodies recognizing LDN, LDN-F and LDN-DF was observed in infected snail tissue, in particular in regions involved in sporocystogenesis, in addition to an enhanced binding of anti-SEA serum and antibodies reacting with F-LDN. A pronounced expression of most of these carbohydrate antigens was also observed at the surface of miracidia. Hence, the detection of shared carbohydrate determinants in uninfected snail tissue, sporocysts and miracidia may support the hypothesis of carbohydrate-based molecular mimicry as a survival strategy of S. mansoni.
By
Thomas M. Habermann, Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55901, USA,
Susan M. Geyer, Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55901, USA
Clinical trials are the backbone of the development and advancement of therapeutic interventions. The pace of development of new agents, the costs of data management, inclusion of quality-of-life assessments, symptom-control assessments and the evaluation of biologic correlates all present significant challenges for the future development of new therapeutic regimens. As these therapeutic regimens become increasingly targeted and our understanding of lymphoma deepens, the identification and assessment of relevant endpoints, be they clinical (e.g. physical examination, radiologic) or biologic (e.g. immunologic, genetic, metabolic etc.), also becomes increasingly complex. In turn, the more complex our endpoints and the more targeted our regimens, the more challenges are presented when designing and conducting clinical trials and analyzing and interpreting their results. While the field of clinical trial design is too broad and widely discussed to adequately give full discussion in this chapter, the reader is referred to more general references on this area. Given the complexity of issues when designing, monitoring, interpreting and analyzing data for a clinical trial, statistician input and collaboration is of paramount importance. This chapter focuses on the principles behind and details of clinical trials from the clinician perspective. As such, we discuss the fundamental considerations when designing trials as well as outline the types of trials typically conducted in clinical research.
BACKGROUND
The practice and science of clinical trials and research is in its relative infancy. Until 1750, the thinking was that of Galen, who attained an authority that remained unchallenged.
Background: Approximately 20 per cent of adult patients presenting to otolaryngology clinics have symptoms pertaining to the inner ear. These are investigated with magnetic resonance imaging (MRI) internal auditory meatus scans. This study analysed all findings from 736 sequential MRI internal auditory meatus scans performed on 731 patients over a one year period.
Methods: Six hundred and seventy-two patients were included for analysis. Of these, 419 (62.35 per cent) had normal MRI scans, 221 (32.90 per cent) had MRI findings thought to be unrelated to their presenting symptoms, 32 (4.76 per cent) had findings thought to be the cause of their symptoms, and eight (1.19 per cent) had the typical appearance of an VIIIth nerve schwannoma.
Conclusions: Magnetic resonance image scanning of the inner ears and auditory pathways yields a diagnosis of VIIIth nerve tumours of the order of 1 per cent, does not show other causes of inner-ear symptoms in a further 4 per cent, and shows incidental intra- and extracranial abnormalities in a further 33 per cent, most of which are not clinically significant.
The longevity of filarial nematodes is dependent on secreted immunomodulatory products. Previous investigation of one such product, ES-62, has suggested a critical role for post-translationally attached phosphorylcholine (PC) moieties. In order to further investigate this, ES-62 lacking PC was produced, using the Pichia pastoris recombinant gene expression system. Unlike parasite-derived ES-62, which is tetrameric the recombinant material was found to consist of a mixture of apparently stable tetramers, dimers and monomers. Nevertheless, the recombinant protein was considered to be an adequate PC-free ES-62 as it was recognized by existing antisera against the parasite-derived protein. However, subsequent to this, recognition of parasite-derived ES-62 by antibodies produced against the recombinant protein was found to be absent. In an attempt to explain this, recombinant ES-62 was subjected to structural analysis and was found to (i) contain 3 changes in amino acid composition; (ii) demonstrate significant alterations in glycosylation; (iii) show major differences in protein secondary structure. The effects of these alterations in relation to the observed change in immunogenicity were investigated and are discussed. The data presented clearly show that recognition by existing antibodies is insufficient proof that recombinant proteins can be used to mimic parasite-derived material in studies on nematode immunology and vaccination.
The developmental expression of the antigenic fucosylated glycan motifs Fucα1-3GalNAcβ1-4GlcNAc (F-LDN), Fucα1-3GalNAcβ1-4(Fucα1-3)GlcNAc (F-LDN-F), GalNAcβ1-4(Fucα1-3)GlcNAc (LDN-F), Galβ1-4(Fucα1-3)GlcNAc (Lewis X), and GalNAcβ1-4(Fucα1-2Fucα1-3)GlcNAc (LDN-DF) in Schistosoma mansoni cercariae, adult worms and eggs, was surveyed using previously defined anti-carbohydrate monoclonal antibodies (mAbs). Lewis X was found both on glycolipids and glycoproteins, yet with completely different expression patterns during the life-cycle: on glycolipids, Lewis X was mainly found in the cercarial stage, while protein-conjugated Lewis X was mainly present in the egg stage. Also protein-conjugated LDN-F and LDN-DF were most highly expressed in the egg-stage. On glycolipids LDN-DF was found in all three examined stages, whereas LDN-F containing glycolipids were restricted to adult worms and eggs. The motifs F-LDN and F-LDN-F were found both on glycoproteins and glycolipids of the cercarial and egg stage, while in the adult stage, they appeared to occur predominantly on glycolipids. Immunofluorescence assays (IFA) showed that these F-LDN and F-LDN-F containing glycolipids were localized in a yet undefined duct or excretory system of adult worms. Murine infection serum showed major reactivity with this adult worm duct-system, which could be fully inhibited by pre-incubation with keyhole limpet haemocyanin (KLH). Clearly, the use of defined mAbs provides a quick and convenient way to map expression profiles of carbohydrate epitopes.
The influence of low concentration (1 mol%) Mg doping on the structural, microstructural, surface morphological and dielectric properties of Ba1-xSrxTiO3 thin films has been measured and analyzed. The films were fabricated on MgO and Pt-Si substrates via the metalorganic solution deposition technique using carboxylate-alkoxide precursors and post deposition annealed at 800 °C (film/MgO substrates) and 750 °C (film/Pt-Si substrates). The structure, microstructure, surface morphology and film/substrate compositional quality were analyzed and correlated to the films dielectric and insulating properties. Dielectric properties of unpatterned films were measured at 10 GHz with a coupled/split dielectric resonator system and at 100 kHz using metal-insulator-metal capacitors. The Mg-doped BST films exhibited improved dielectric loss and insulating characteristics compared to the undoped Ba0.6Sr0.4TiO3 thin films. The improved dielectric properties, low leakage current, and good tunability of the low level Mgdoped BST thin films merit strong potential for utilization in microwave tunable devices.
The mechanical behavior of a thin film that is clamped to an elastically hard substrate can be compared to a bulk metal by studying the absorption of hydrogen. Since hydrogen is dissolved in interstitial sites and exerts force on neighboring metal atoms, the in-plane stresses increase with increasing hydrogen concentration. In the case of Nb-films covered with a thin Pd layer, stresses of several GPa were measured. Nb and Pd films prepared by evaporation were loaded with hydrogen. Out-of-plane strain and in-plane stresses during electrolytic loading with hydrogen were determined by performing x-ray diffraction and substrate curvature measurements. At low H-concentrations the developing stresses correspond to a clamped film expanding elastically out-of-plane only. Above a critical H-concentration the films deform plastically. In some cases the critical hydrogen concentration corresponds to the terminal H-solubility, above which the hydride precipitates by emission of extrinsic dislocation loops. For the remaining cases a critical stress is reached before passing the phase boundary, which leads to the formation of misfit dislocations at the interface between film and substrate. The concomitant slip lines were observed on the surface of a Gd (0001) film using Scanning Tunneling Microscopy. An additional surface pattern that can be correlated with emitted dislocation loops was observed.