Understanding and managing myeloma.

Multiple myeloma cannot be cured and treatment can be complex. This article outlines the pathophysiology of the condition, together with the diagnostic process and the available treatment options.

Understanding the role of activated sludge in oxygen transfer: Effects of sludge settleability, solids retention time, and nitrification reaction.

The current understanding on the oxygen transfer in activated sludge process is primarily developed based on two-phase systems, focusing only on oxygen transfer from air to water. However, this research demonstrates that activated sludge particles significantly impact oxygen transfer from air all the way to the microorganisms. Three bench-scale complete-mix activated sludge reactors, operated under the same influent loading and dissolved oxygen level but different solids retention times (SRTs), were used to develop oxygen transfer performance data as effects of different sludge property parameters. These reactors were also operated under batch modes to further validate the effect of nitrification reaction on oxygen transfer. Results indicate that high overall oxygen transfer efficiency (OTE) is associated with low mixed liquor viscosity, long SRT, and nitrification reaction. Further analyses suggest that low mixed liquor viscosity, which resulted from high sludge settleability or low settled volume of sludge, reduces the thickness of liquid films at all interfaces and the size of air bubbles. Long SRT results in high active nitrifier population and low specific extracellular polymeric substance (EPS). Nitrification reaction, which serves as the rate-limiting step for oxygen transfer, may increase the oxygen transfer driving force. High active nitrifier population also promotes direct air-sludge contact. All of these factors help facilitate oxygen transfer. This research provides a new approach to improve energy efficiency for wastewater treatment, which is to change the activated sludge property by adjusting treatment plant design and operational parameters. PRACTITIONER POINTS: High sludge settleability reduces viscosity therefore liquid film thickness. Long SRT increases active microorganism population and reduces specific EPS content. Nitrification reaction increases oxygen transfer driving force. Direct air-particle contact adds another pathway for oxygen transfer. Nitrification reaction is the rate-limiting step of the oxygen transfer process.

Implementation of long solids retention time activated sludge process for rural residential community.

Most rural communities in the United States are facing increasingly rigorous effluent criteria, especially ammonia, for their wastewater treatment facilities. A new baffled bioreactor (BBR) technology, which employs a preanoxic activated sludge process operated with a long solids retention time (SRT), was installed in a small community in Missouri to address the more stringent effluent limits. In a recent full-year normal operation cycle (2018), the average effluent concentrations of BOD5 , TSS, and ammonia-nitrogen were 3.2, 2.2, and 0.5 mg/L, respectively, with removal efficiencies of 96%, 85%, and 98%, respectively. All these parameters were significantly better than their respective permit limits. The long SRT afforded an enhanced factor of safety for the process, conferring the ability to nitrify at sustained ambient temperatures as low as -22°C. Long SRT also resulted in significant reductions in waste sludge production, resulting in dramatically reduced operational costs for sludge handling. Ultimately, the long SRT activated sludge process afforded the ability to meet stringent effluent quality standards including ammonia and the numerous unique challenges that are inherent to small flows. PRACTITIONER POINTS: Small community hydraulic and mass loadings are highly variable and difficult to quantify during facility design. A long SRT activated sludge process warrants superior performance and enhanced factor of safety. The long SRT process with preanoxic zones generated no excess sludge during the extended operation period, significantly simplifying plant operation. Long SRT process is well suited to accommodate wastewater variability associated with small communities while maintaining superior treatment quality.

Implementation of an early rule-out pathway for myocardial infarction using a high-sensitivity cardiac troponin T assay.

OBJECTIVES: Patients with suspected acute coronary syndrome and high-sensitivity cardiac troponin (hs-cTn) concentrations below the limit of detection at presentation are low risk. We aim to determine whether implementing this approach facilitates the safe early discharge of patients. METHODS: In a prospective single-centre cohort study, consecutive patients with suspected acute coronary syndrome were included before (standard care) and after (intervention) implementation of an early rule-out pathway. During standard care, myocardial infarction was ruled out if hs-cTnT concentrations were <99th centile (14 ng/L) at presentation and at 6-12 hours after symptom onset. In the intervention, patients were ruled out if hs-cTnT concentrations were <5 ng/L at presentation and symptoms present for ≥3 hours or were ≥5 ng/L and unchanged within the reference range at 3 hours. We compared duration of stay (efficacy) and all-cause death at 1 year (safety) before and after implementation. RESULTS: We included 10 315 consecutive patients (64±16 years, 46% women) with 6642 (64%) and 3673 (36%) in the standard care and intervention groups, respectively. Duration of stay was reduced from 534 (IQR, 220-2279) to 390 (IQR, 218-1910) min (p<0.001) after implementation. At 1 year, all-cause death occurred in 10.9% (721 of 6642) and 10.4% (381 of 3673) of patients in the standard care group (referent) and intervention group, respectively (adjusted OR 1.02, 95% CI 0.88 to 1.18). CONCLUSION: In patients with suspected acute coronary syndrome, implementing an early rule-out pathway using hs-cTnT concentrations <5 ng/L at presentation reduced the duration of stay in hospital without compromising safety.

Filamentous organisms degrade oxygen transfer efficiency by increasing mixed liquor apparent viscosity: Mechanistic understanding and experimental verification.

Recent findings have demonstrated that activated sludge morphology significantly impacts oxygen transfer efficiency (OTE) in the activated sludge process. In this study, we developed a mechanistic understanding of this impact. Mixed liquor samples collected from a domestic wastewater treatment plant (WWTP) were blended with a bulking activated sludge from a bench scale reactor (BSR) cultured on synthetic wastewater to manipulate various morphological parameters such as the settled sludge volume (SV), the sludge volume index (SVI), and the specific filament length (SFL). The filaments that were present in the blended sludges consisted largely of Type 0041 and Type 021N, which are commonly found in WWTPs that treat domestic wastewater. Variations in sludge morphology, as quantified by settled sludge volume after 30 min (SV30), SVI, and SFL, systematically affected the mixed liquor apparent viscosity (µapp), which consequently impacted OTE. An increase in the SFL from 9.61 × 106 µm g-1 to 6.88 × 107 µm g-1 resulted in a 41.4% increase in apparent viscosity and a 24.6% decrease in volumetric mass transfer coefficient (KLa). A new parameter, named the ultimate settleability (SVULT), was developed by curve fitting the SV versus time data and found to relate with µapp through an expanded form of the Einstein Equation for the viscosity. Therefore, SVULT is a corollary for the particle volume fraction that incorporates effects of both the sludge morphology and mass concentration on µapp. Theoretical derivation revealed that an increase in SVULT resulted in an increase in µapp, which reduced oxygen transfer by increasing the air bubble size and reducing refreshment of the liquid at the gas-liquid interface. The KLa was found to be inversely proportional to µapp0.75 through fitting the experimental data with the theoretical model. Using a variance-based global sensitivity analysis, three operating parameters that have the most impact on oxygen transfer were identified: the power input per unit volume, the superficial gas flowrate, and the µapp.

KBTBD13 is an actin-binding protein that modulates muscle kinetics.

The mechanisms that modulate the kinetics of muscle relaxation are critically important for muscle function. A prime example of the impact of impaired relaxation kinetics is nemaline myopathy caused by mutations in KBTBD13 (NEM6). In addition to weakness, NEM6 patients have slow muscle relaxation, compromising contractility and daily life activities. The role of KBTBD13 in muscle is unknown, and the pathomechanism underlying NEM6 is undetermined. A combination of transcranial magnetic stimulation-induced muscle relaxation, muscle fiber- and sarcomere-contractility assays, low-angle x-ray diffraction, and superresolution microscopy revealed that the impaired muscle-relaxation kinetics in NEM6 patients are caused by structural changes in the thin filament, a sarcomeric microstructure. Using homology modeling and binding and contractility assays with recombinant KBTBD13, Kbtbd13-knockout and Kbtbd13R408C-knockin mouse models, and a GFP-labeled Kbtbd13-transgenic zebrafish model, we discovered that KBTBD13 binds to actin - a major constituent of the thin filament - and that mutations in KBTBD13 cause structural changes impairing muscle-relaxation kinetics. We propose that this actin-based impaired relaxation is central to NEM6 pathology.

Assessing activated sludge morphology and oxygen transfer performance using image analysis.

The morphology of the microbial communities can have dramatic impacts on not only the treatment performance, but also the energy use performance of an activated sludge process. In this research, we developed and calibrated an image analysis technique to determine key morphological parameters such as the floc diameter and the specific filament length (SFL) and discovered that the SFL has significant impacts on sludge floc size, the specific extracellular polymeric substances production, the settleability, mixed liquor viscosity, and oxygen transfer efficiency. When the SFL increased from 2.5 × 109 µm g-1 to 6.0 × 1010 µm g-1, the apparent viscosity normalized by the mixed liquor suspended solids concentration increased by 67%, and the oxygen transfer efficiency decreased by 29%. A long solids retention time (SRT) of 40 day reduced SFL, improved sludge settling performance, and improved oxygen transfer efficiency as compared to shorter SRTs of 10 and 20 day. The findings underscore the need to assess microbial morphology when quantifying the treatment performance and energy performance of activated sludge processes.

Activated sludge morphology significantly impacts oxygen transfer at the air-liquid boundary.

Oxygen transfer is a key process determining the energy use of a biological wastewater treatment process. In this research, we investigated the effect of sludge morphology, especially the role of filamentous microorganisms, on oxygen transfer using bench-scale complete-mix activated sludge reactors with solids retention times (SRTs) of 10-, 20-, and 40-days, respectively. Results indicated 5%-10% reduced aeration need in the 40-day SRT reactor, compared with 10- and 20-day SRT reactors to maintain the same dissolved oxygen level, due to the improvement in sludge settleability and oxygen transfer efficiency (OTE). Filamentous microorganisms adversely impacted OTE via an increase in apparent viscosity of the mixed liquor, which resulted in an increase in the air bubble size and liquid film thickness and, therefore, limited oxygen transfer at the air-liquid boundary. A statistical analysis also confirmed that the mixed liquor viscosity is a statistically significant parameter links to OTE. PRACTITIONER POINTS: Filamentous organisms reduce oxygen transfer via increasing mixed liquor viscosity, which increases air bubble size and liquid film thickness at the air-liquid boundary. Increasing solids retention time reduces filament density. As a result, very long solids retention time promotes oxygen transfer.

Exploring the non-viral infectious causes of cancer.

This article discusses the contribution made by non-viral infections to the global burden of cancer and describes the bacterial, protozoan and fungal organisms that are believed to cause cancer, either directly or indirectly.

Preventing cervical cancer by vaccinating against HPV.

There was widespread media interest in a report on the successful results from a trial of a vaccine against virus strains responsible for cervical cancer. This article examines the background to the report, considers the actual outcomes and comments on the significance and likely impact of the vaccine.

Laboratory diagnosis and investigation of anaemia.

Anaemia is one of the most common conditions encountered in clinical practice. This article outlines the methods used to investigate anaemia and discusses the significance of laboratory diagnosis in treating this condition.

Myeloma: its diagnosis and treatment.

There are 2,500 new cases of myeloma in the UK every year. This article describes the epidemiology of the disease and its clinical features, and outlines the treatments available and the likely prognosis.

Pathophysiology of anaemia.

Anaemia is a common condition in which all forms can be defined on the basis of physiological mechanisms. There are three broad categories: decreased/defective red blood cell production; increased loss/destruction of red blood cells; and a mixture where both mechanisms operate simultaneously.

Anaemia: causes and treatment.

Anaemia is a common pathological condition and it is important that all nurses are aware of its signs and symptoms. It can be detected by screening and, in most instances, readily and cheaply treated. Identifying the underlying cause of the anaemia is vital, as this will ensure that the patient receives appropriate treatment, which can have a significant impact on quality of life.

Revised advice on use of imatinib for chronic myeloid leukaemia.

NICE guidance that imatinib be available to all patients newly diagnosed with chronic myeloid leukaemia has been welcomed by clinicians and patient groups. The drug is expected to transform the management of CML.

Genetic knock-down of HDAC3 does not modify disease-related phenotypes in a mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by an expansion of a CAG/polyglutamine repeat for which there are no disease modifying treatments. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression and has been recapitulated across multiple HD models. Altered histone acetylation has been proposed to underlie this transcriptional dysregulation and histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA), have been shown to improve polyglutamine-dependent phenotypes in numerous HD models. However potent pan-HDAC inhibitors such as SAHA display toxic side-effects. To better understand the mechanism underlying this potential therapeutic benefit and to dissociate the beneficial and toxic effects of SAHA, we set out to identify the specific HDAC(s) involved in this process. For this purpose, we are exploring the effect of the genetic reduction of specific HDACs on HD-related phenotypes in the R6/2 mouse model of HD. The study presented here focuses on HDAC3, which, as a class I HDAC, is one of the preferred targets of SAHA and is directly involved in histone deacetylation. To evaluate a potential benefit of Hdac3 genetic reduction in R6/2, we generated a mouse carrying a critical deletion in the Hdac3 gene. We confirmed that the complete knock-out of Hdac3 is embryonic lethal. To test the effects of HDAC3 inhibition, we used Hdac3(+/-) heterozygotes to reduce nuclear HDAC3 levels in R6/2 mice. We found that Hdac3 knock-down does not ameliorate physiological or behavioural phenotypes and has no effect on molecular changes including dysregulated transcripts. We conclude that HDAC3 should not be considered as the major mediator of the beneficial effect induced by SAHA and other HDAC inhibitors in HD.