Determination of fluidized bed granulation end point using near-infrared spectroscopy and phenomenological analysis

Simultaneous real-time monitoring of particle size and moisture content by near-infrared spectroscopy through a window into the bed of a fluidized bed granulator is used to determine the granulation end point. The moisture content and particle size determined by the near-infrared monitor correlates well with off-line moisture content and particle size measurements. The measured particle size is modeled using a population balance approach, and the moisture content is shown to follow accepted models during drying. Given a known formulation, with predefined parameters for peak moisture content, final moisture content, and final granule size, the near-infrared monitoring system can be used to control a fluidized bed granulation by determining when binder addition should be stopped and when drying of the granules is complete.     

Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia

Introduction

De-escalation therapy is a strategy currently used for the management of nosocomial pneumonia. In this study, we evaluated clinical outcomes and risk factors related to de-escalation therapy in patients with intensive care unit (ICU)-acquired pneumonia.

Methods

This was a retrospective observational cohort study of ICU patients who developed pneumonia more than 48 hours after admission to the ICU at Samsung Medical Center from September 2004 to December 2007.

Results

The 137 patients comprised 44 (32.1%) who received de-escalation therapy and 93 in the non-de-escalation group. The de-escalation group showed a lower pneumonia-related mortality rate than the non-de-escalation group by day 14 (2.3% vs. 10.8%, respectively; P = 0.08) and by day 30 (2.3% vs. 14%, respectively; P = 0.03) after the diagnosis of pneumonia. The variables independently associated with ICU-acquired pneumonia-related mortality included the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the modified Clinical Pulmonary Infection Score (CPIS) after 5 days with pneumonia. The non-de-escalation group had significantly higher APACHE II score and modified CPIS after 5 days with ICU-acquired pneumonia compared to the de-escalation group. Among all patients, 20.4% (28 of 137) had negative cultures for pathogens, and 42.9% (12 of 28) received de-escalation therapy. The latter 12 patients received de-escalation therapy and survived 30 days after the diagnosis of pneumonia.

Conclusions

Patients in the de-escalation group showed a significantly lower mortality rate compared to patients in the non-de-escalation group. De-escalation therapy can be safely provided to patients with ICU-acquired pneumonia if they are clinically stable by day 5, even in those whose respiratory specimen cultures yield no specific pathogens.     

Estimated blood pressure trajectories and hypertension patterns among pregnant women living with HIV,Haiti, 2007–2017

Hypertension in pregnancy is a key driver of mortality and morbidity among Haitian women. HIV infection and treatment may worsen hypertension and increase cardiovascular disease risk. The authors examined blood pressure and hypertension patterns among 1965 women (2306 pregnancies ending in live births) in a prevention of maternal‐to‐child transmission (PMTCT) program in Port‐au‐Prince, Haiti, between 2007 and 2017. Hypertension was defined as blood pressure ≥140/90 mm Hg on two consecutive visits. Latent class analysis assessed trajectories of mean arterial pressure (MAP) and multinomial ordinal logistic regression examined factors associated with higher trajectories. Between 2007–2009 and 2013–2016, hypertension at PMTCT entry increased from 1.3% to 3.8% (p = .005), while incidence at any time during PMTCT follow‐up increased from 5.0 to 16.1 per 100 person‐years (p < .001). Hypertension detected ≤20 weeks and > 20 weeks of gestation (possible gestational hypertension) increased from 1.1% to 3.5% (p = .003) and from 2.3% to 6.9% (p < .001), respectively. Five MAP trajectories ranged from low‐stable to high‐increasing. In multivariable analysis controlling for history of antiretroviral therapy, age, parity, and weight, program entry in more recent years was associated with greater odds of higher MAP trajectory (adjusted odds ratio for 2013–2016 vs. 2007–2009 = 3.1, 95% confidence interval: 1.7–5.6). The increasing prevalence and incidence of hypertension highlight a need for screening and management prior to PMTCT entry and during follow‐up. In a population with limited access to chronic disease care, and where many deliveries occur outside of a clinical setting, the period of PMTCT follow‐up represents an opportunity to diagnose and initiate management of preexisting and pregnancy‐related hypertension.     

EAACI Biologicals Guidelines—dupilumab for children and adults with moderate-to-severe atopic dermatitis

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed.     

Lack of shared lymphocyte-stimulating determinants between H-2I and HLA-D/DR using mouse primed lymphocyte typing cells

A number of anti-H-2 alloantisera containing antibody reactive with I region gene products (Ia) of the major histocompatibility complex cross-react with determinants expressed by human peripheral blood B lymphocytes. Such data have led to the conclusion that Ia and DR antigens share cross-reacting determinants. We have attempted to generate mouse primed T lymphocyte populations specific for defined I region gene product determinants which concomitantly recognize DR determinants on human peripheral blood leukocytes in primed lymphocyte typing (PLT) analysis. Mouse PLT cells were generated in primary MLC using strain combinations identical to those in which positive mouse/human cross-reacting antisera have been obtained. The resulting PLT cells exhibited strong, yet specific, secondary MLC responses against mouse cells expressing the Ia determinants used as the primary stimulus. In contrast, when examined on panels of human peripheral blood leukocytes, no reactivity was detected. This lack of cross-reactivity suggests that mouse T cells primed toward Ia determinants do not regularly recognize cross-reacting determinants of DR or D-associated antigens expressed on human PBLs. Consequently, mPLT cells are not a useful reagent in defining HLA-D region polymorphism.     

Magnetically-labeled sensitized splenocytes to identify glioma by MRI: a preliminary study.

This study investigated the feasibility of imaging the migration and incorporation of magnetically-labeled sensitized splenocytes in an experimental 9L glioma brain tumor model. Splenocytes collected from tumor-bearing (sensitized splenocytes) or control (nonsensitized splenocytes) host rats were analyzed to determine the population of different cells, labeled with ferumoxides-protamine sulfate (FePro) and injected intravenously to recipient rats (N=4, for each group) bearing intracranial 9L tumors. Day 3 postinjection of splenocytes multiecho T2*-weighted and three-dimensional (3D) gradient echo MRI were obtained using a 7 Tesla MR system. R2* (1/T2*) maps were created from the T2*-weighted images. Signal intensities (SIs) and R2* values in the tumors and contralateral brain were determined by hand drawn regions of interest (ROIs). Brain sections were stained for the evidence of administered cells. Both 3D and T2*-weighted MRI showed low signal intensity areas in and around the tumors in rats that received labeled sensitized splenocytes. Prussian blue (PB), CD45- and CD8-positive cells were present in areas at the corresponding sites of low signal intensities seen on MRI. Rats that received labeled nonsensitized splenocytes did not show low signal intensity areas or PB positive cells in or around the implanted tumors. In conclusion, the immunogenic reaction can be exploited to delineate recurrent glioma using MRI following systemically delivered magnetically labeled sensitized splenocytes or T-cells.     

Energetics of B-to-Z transition in DNA.

Analysis by two-dimensional gel electrophoresis of topoisomers of plasmids containing d(pCpG)n . d(pCpG)n inserts, in which n ranges between 8 and 21, shows that the B-to-Z transition within the alternating C-G is readily induced by negative supercoiling and is highly cooperative. The free energy parameters for the transition in dilute aqueous buffers have been evaluated from a statistical mechanical analysis of the data, and these parameters allow prediction of the superhelicities of plasmids at which the transition occurs in alternating C-G inserts over a wide range of lengths. In agreement with the crystal structures, the helical handedness of the B structure in solution and that of the Z structure are shown to be opposite to each other. Furthermore, it is found that the B form of the alternating C-G sequence in solution has a helical periodicity of 10.5 +/- 0.1 base pairs per turn, and the Z form has a helical periodicity of 11.6 +/- 0.3 base pairs per turn. There also appears to be a significant unwinding of the right-handed DNA duplex at each of the B/Z junctions.