Quality Improvement Initiative to Reduce Nighttime Noise in a Transplantation and Cellular Therapy Unit

Sleep is an essential biologic function vital for physiologic rest, healing, and emotional well-being. Sleep disruption is commonly seen in patients and caregivers with lengthy hospital stays such as patients undergoing hematopoietic stem cell transplantation and cellular therapy (TCT). Sleep disruption can lead to increased stress and fatigue, affecting caregivers’ ability to support their loved one. The global aim of our quality improvement initiative was to improve sleep quality in TCT patients and caregivers. The smart aim of our project was to decrease nighttime hallway noise from 47 dB to 43 dB and decrease the number of overnight noise peaks greater than 60 dB from 865 to 432 in 6 months. Through a cross-sectional quantitative and qualitative evaluation of sleep we had previously identified poor sleep quality, and with a cross-sectional focus group analysis of patients, caregivers, and medical staff we identified the factors associated with poor sleep. Hallway noise was a major factor. A simplified failure mode analysis identified 4 main key drivers; unobtrusive nighttime cleaning process, nighttime awareness maintenance system, quiet nighttime nursing system, and reliable nighttime awareness system. Several plan-do-study-act interventions took place and were adopted. From January to June 2018 the overnight mean decibel level decreased from 47 dB to 44 dB (6% reduction). Overnight noise spikes above 60 dB decreased from a mean of 865 spikes to a mean of 463 spikes (46% reduction). With a quality improvement initiative, we identified the causes of hallway nighttime hospital unit noise that negatively impact sleep and through a team-based approach performed interventions that successfully mitigated these factors.     

Relationship between fibronectin and lymphoid cells in buccal mucosa, labial salivary glands and palatine tonsil

The distribution of fibronectin in human buccal mucosa and labial salivary glands and its relationship to lymphoid cells was studied using an immunoperoxidase technique and monoclonal and polyclonal antibodies. In all specimens fibronectin was associated with basement membranes of epithelia, vascular endothelium and perineural sheaths. In histologically normal areas of buccal mucosa fibronectin was distributed as a sparse network in the superficial lamina propria. A more extensive network of fibronectin was found within the lamina propria of mucosal specimens infiltrated with T lymphocytes, whereas fibronectin was absent in areas occupied by B lymphocytes. A similar relationship between lymphocyte type and the presence of a fibronectin network was found in labial glands and palatine tonsil. Fibronectin was not detected within oral, salivary gland, tonsillar crypt or capsular epithelium.     

Tropical countries may be willing to pay more to protect their forests

Inadequate funding from developed countries has hampered international efforts to conserve biodiversity in tropical forests. We present two complementary research approaches that reveal a significant increase in public demand for conservation within tropical developing countries as those countries reach upper-middle-income (UMI) status. We highlight UMI tropical countries because they contain nearly four-fifths of tropical primary forests, which are rich in biodiversity and stored carbon. The first approach is a set of statistical analyses of various cross-country conservation indicators, which suggests that protective government policies have lagged behind the increase in public demand in these countries. The second approach is a case study from Malaysia, which reveals in a more integrated fashion the linkages from rising household income to increased household willingness to pay for conservation, nongovernmental organization activity, and delayed government action. Our findings suggest that domestic funding in UMI tropical countries can play a larger role in (i) closing the funding gap for tropical forest conservation, and (ii) paying for supplementary conservation actions linked to international payments for reduced greenhouse gas emissions from deforestation and forest degradation in tropical countries.Primary forests—“forests of native species in which there are no clearly visible signs of past or present human activity” (ref. 1, p. 11)—are globally significant repositories of biodiversity (2) and carbon (3). The global area of these forests is declining at an annual percentage rate that is nearly triple the rate for total global forest area (ref. 1, tables 2.4 and 3.3). Virtually all of the loss is occurring in tropical countries (SI Text, section 1). Logging is the main cause of the loss (ref. 1, p. 27), but hunting threatens biodiversity even in primary forests with intact tree cover (4, 5).Protecting primary tropical forests is a core mission of several international institutions created since the early 1990s, including the Convention on Biological Diversity (CBD), the Global Environment Facility (GEF), and the UN Collaborative Program on Reducing Emissions from Deforestation and Forest Degradation in Developing Countries (REDD). However, the CBD failed to achieve its goal of significantly reducing biodiversity loss by 2010 (6); international funding for biodiversity protection through the GEF and other mechanisms is below commitments made at the 1992 Earth Summit (7) and the amounts required to achieve the CBD’s 2020 protection targets (8); and REDD has not advanced beyond a readiness phase (www.un-redd.org). Relying on international mechanisms to fund protection of primary tropical forests does not look like a winning strategy.Here, we argue that economic development during the past 20–25 y has raised public demand for forest protection within tropical countries, but the level of protection supplied by tropical country governments has not kept pace. We focus on the dynamics of conservation and development within relatively wealthier developing countries: The group that is classified by the World Bank as upper-middle income (UMI). As we will show, the majority of primary forest area in tropical countries is found in these countries. We hypothesize that public willingness to pay (WTP) to protect forests has reached a relatively high level in UMI countries, leading to greater support for local conservation nongovernmental organizations (NGOs) and prompting governments to boost forest protection efforts—but not as much as the public would like. This gap between domestic demand and domestic supply of forest protection has two important implications: Domestic funding might be sufficient to cover the costs of additional protection in some, and perhaps many, tropical countries; and international funding might be able to leverage more domestic funding than it currently does.Although many cross-country studies in the environmental Kuznets curve (EKC) literature have investigated the effect of rising national income on deforestation (9), none has considered the effect on primary forests. This gap matters because deforestation, unlike primary forest loss, results mainly from agricultural conversion, not logging (1, 10). A few cross-country studies have considered the effect of national income on creation of protected areas (11–16), but with mixed findings on the significance of the effect. A second and larger group of studies has used surveys to measure WTP for biodiversity conservation by domestic populations within particular countries. Most of these studies have failed to detect a significant income effect (P < 0.05) (17, 18). Metaanalyses of these studies estimate income effects that are generally positive (protection increases with income) but not necessarily statistically significant (17, 18).We extended this prior work by coupling two research approaches: a broad-brush statistical analysis of the association between a standard measure of economic development, i.e., per capita gross national income (GNI), and a large set of cross-country conservation indicators (CIs); and a focused investigation of forest protection in a particular UMI country, Malaysia. The statistical analysis spanned 12 indicators from 10 diverse sources (Materials and Methods and SI Text, section 1). The indicators pertained to public environmental preferences, conservation NGOs, and government action (conservation spending, protected area establishment). These indicators relate more directly to our hypothesis about domestic demand and domestic supply of forest protection than do the deforestation rates analyzed by EKC studies. We limited the samples to countries classified as tropical by the UN Food and Agriculture Organization Forestry Department (ref. 19, data table 2) and paid special attention to differences between tropical countries in the UMI group and ones in lower income groups.The Malaysian case study allowed us to examine more closely the linkages from rising household income to increased household WTP, NGO engagement, and government protective action, and thereby uncover reasons for the underprovision of forest protection relative to household preferences. The case concerned Belum–Temengor, a 300,000-ha forested region in the state of Perak (Fig. 1). This region contains the largest area of primary forest in Peninsular Malaysia outside a national park. Our research included a population-representative survey of 1,261 rural and urban households in the Malaysian state of Selangor and the federal territory of Kuala Lumpur during 2010 (Materials and Methods). We used choice experiments (20, 21) to estimate household WTP to protect Belum–Temengor against logging and poaching (SI Text, section 2). Information from the case study enabled us to compare the public’s aggregate WTP for protection to current protection expenditures and to discuss why there is a gap between the two.Open in a separate windowFig. 1.Locations of Belum–Temengor (site of forest protection plans in choice experiments) and Selangor and Kuala Lumpur (site of household survey; the black dot is Kuala Lumpur) within Peninsular Malaysia (light gray). Lines show Malaysian state boundaries. Sources: base map, GADM database (www.gadm.org); Belum–Temengor boundaries, Forest Research Institute Malaysia.     

Anti-stigma training and positive changes in mental illness stigma outcomes in medical students in ten countries: a mediation analysis on pathways via empathy development and anxiety reduction

Purpose

Studies of mental illness stigma reduction interventions have been criticised for failing to evaluate behavioural outcomes and mechanisms of action. This project evaluates training for medical students entitled ‘Responding to Experienced and Anticipated Discrimination’ (READ), developed to focus on skills in addition to attitudes and knowledge. We aimed to (i) evaluate the effectiveness of READ with respect to knowledge, attitudes, and clinical communication skills in responding to mental illness-related discrimination, and (ii) investigate whether its potential effectiveness was mediated via empathy or/and intergroup anxiety.

Methods

This is an international multisite non-randomised pre- vs post-controlled study. Eligible medical students were currently undertaking their rotational training in psychiatry. Thirteen sites across ten countries (n = 570) were included in the final analysis.

Results

READ was associated with positive changes in knowledge (mean difference 1.35; 95% CI 0.87 to 1.82), attitudes (mean difference − 2.50; 95% CI − 3.54 to − 1.46), skills (odds ratio 2.98; 95% CI 1.90 to 4.67), and simulated patient perceived empathy (mean difference 3.05; 95% CI 1.90 to 4.21). The associations of READ with knowledge, attitudes, and communication skills but not with simulated patient perceived empathy were partly mediated through student reported empathy and intergroup anxiety.

Conclusion

This is the first study to identify mediating effects of reduced intergroup anxiety and increased empathy in an evaluation of anti-stigma training that includes behavioural measures in the form of communication skills and perceived empathy. It shows the importance of both mediators for all of knowledge, skills, and attitudes, and hence of targeting both in future interventions.

     

Postprandial substrate deposition in human forearm and adipose tissues in vivo

1. Substrate movements in forearm muscle and subcutaneous adipose tissue were studied, by measurement of arteriovenous differences and blood flow, in seven normal subjects after an overnight fast and then for 6 h after ingestion of a mixed meal. Overall substrate balances were examined in terms of the flux of gram-atoms of carbon. 2. As found previously, the forearm was approximately in carbon balance (import equal to export) after the overnight fast, whereas adipose tissue was a net exporter of carbon, mainly in the form of non-esterified fatty acids. 3. After the meal, arterialized plasma concentrations of glucose and lactate rose sharply (peak at 60 min), whereas those of non-esterified fatty acids and glycerol fell (nadir at 60-120 min). Plasma triacylglycerol concentrations rose slowly to peak at 240 min;much of this rise was accounted for by a rise in the chylomicron fraction. 4. Both tissues took up glucose at an increased rate after the meal. Release of non-esterified fatty acids and glycerol from adipose tissue was suppressed. Clearance of triacylglycerol by both tissues increased after the meal, but was more marked in adipose tissue, where the fractional extraction of chylomicron-triacylglycerol reached 44% at 240 min. 5. The forearm rapidly became a considerable net importer of carbon, and remained so until 6 h after the meal when it was again in approximate carbon balance. Glucose uptake dominated the forearm carbon balance. Adipose tissue was a net importer of carbon from 30 min until 5 h after the meal and then reverted to net export. Clearance of triacylglycerol carbon made the largest contribution to this positive balance, but towards the end of the study this was increasingly counterbalanced by simultaneous non-esterified fatty acid release.     

Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog.

We determined human and canine plasma clearance of atrial natriuretic factor (ANF) by lung, liver, and kidney from arteriovenous differences in plasma ANF and measured organ plasma flow. Human subjects had lower plasma ANF concentrations in the pulmonary vein or the pulmonary capillary wedge position when compared with the pulmonary artery, and both sites yielded pulmonary ANF extraction ratios of 24%. Canine lung ANF extraction was 19 +/- 3% and pulmonary ANF clearance was 328 +/- 78 ml/min per m2 vs. 357 +/- 53 ml/min per m2 in man. Hepatic plasma ANF clearance was 216 +/- 26 ml/min with an extraction ratio of 30 +/- 3% in humans and 199 +/- 89 ml/min and 36 +/- 6% in the dog. Renal plasma ANF clearance in human subjects was 78 +/- 12 ml/min per kidney and correlated well with each kidney's creatinine clearance (r = 0.58, P less than 0.05). The mean renal ANF extraction ratio was 35 +/- 4% in human subjects and 42 +/- 6% in the dog. These data quantitate the specific organ ANF clearances by lung, liver, and kidney in human subjects and in dogs and provide a rationale for elevated plasma ANF levels in cirrhosis, renal failure, and diseases accompanied by reduced perfusion of these organs. These findings support the conclusion that plasma ANF concentrations are dependent upon both the stimuli for ANF secretion as well as the specific organ clearances of ANF.     

Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist

The preclinical pharmacology and pharmacokinetic properties of (2R)-6-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)chromane-2-carboxamide (AZD3783), a potent 5-hydroxytryptamine 1B (5-HT(1B)) receptor antagonist, were characterized as part of translational pharmacokinetic/pharmacodynamic hypothesis testing in human clinical trials. The affinity of AZD3783 to the 5-HT(1B) receptor was measured in vitro by using membrane preparations containing recombinant human or guinea pig 5-HT(1B) receptors and in native guinea pig brain tissue. In vivo antagonist potency of AZD3783 for the 5HT(1B) receptor was investigated by measuring the blockade of 5-HT(1B) agonist-induced guinea pig hypothermia. The anxiolytic-like potency was assessed using the suppression of separation-induced vocalization in guinea pig pups. The affinity of AZD3783 for human and guinea pig 5-HT(1B) receptor (K(i), 12.5 and 11.1 nM, respectively) was similar to unbound plasma EC(50) values for guinea pig receptor occupancy (11 nM) and reduction of agonist-induced hypothermia (18 nM) in guinea pig. Active doses of AZD3783 in the hypothermia assay were similar to doses that reduced separation-induced vocalization in guinea pig pups. AZD3783 demonstrated favorable pharmacokinetic properties. The predicted pharmacokinetic parameters (total plasma clearance, 6.5 ml/min/kg; steady-state volume of distribution, 6.4 l/kg) were within 2-fold of the values observed in healthy male volunteers after a single 20-mg oral dose. This investigation presents a direct link between AZD3783 in vitro affinity and in vivo receptor occupancy to preclinical disease model efficacy. Together with predicted human pharmacokinetic properties, we have provided a model for the quantitative translational pharmacology of AZD3783 that increases confidence in the optimal human receptor occupancy required for antidepressant and anxiolytic effects in patients.     

Secretion of Calcitonin in Hypocalcemic States in Man

The control of calcitonin secretion in humans has been studied extensively only in patients with medullary thyroid carcinoma since the peripheral concentration of the hormone in normal subjects is too low for accurate measurement by existing assay procedures. However, we have recently found that the concentrations of calcitonin in the peripheral plasma of hypocalcemic subjects during provocative tests of hormone secretion were high enough to be measured by radioimmunoassay. Accordingly, the effect of calcium and pentagastrin infusions on plasma calcitonin was studied in nine patients with pseudohypoparathyroidism, seven patients with idiopathic hypoparathyroidism, and six patients with hypocalcemia not due to parathyroid disease. The infusion of calcium in these hypocalcemic subjects resulted in increases in plasma calcitonin to levels that could be readily detected by our radioimmunoassay. Pentagastrin infusion also caused an increase of plasma calcitonin in some subjects, but calcium was approximately 10 times more effective than gastrin in its stimulatory effect on hormone secretion. These results demonstrate that in humans as well as other mammals the secretion of calcitonin by parafollicular cells that are not involved by medullary thyroid carcinoma is directly related to plasma calcium and that gastrin can also stimulate hormone secretion. The results are consistent with the thesis that the secretion of calcitonin by normal human subjects does occur but at peripheral concentrations of the hormone below the detection limits of most existing immunoassays; hypocalcemia leads to increased stores of hormone that can be related by the appropriate stimuli.     

Surprisingly uneven distribution of the T cell receptor V beta repertoire in wild mice

We have examined TCR V beta expression in a collection of wild mice. Many of the mice were homozygous for a large deletion at the V beta locus, and many animals also suppressed expression of several V betas using self superantigens. Expression of V beta 8.2 was unexpectedly suppressed by a self superantigen in some wild mice, which was due to the presence in these animals of a variant V beta 8.2 gene. The amino acid changes in this gene product suggest contact sites between V beta and the superantigen. Although all V betas are expressed within each wild mouse population, individual mice have a limited and variable V beta repertoire. The independent origin of multiple V beta deletions and the presence of polymorphic self superantigens suggest that this variation may be maintained by balancing selection.