Analysis of current state, gaps, and opportunities for technologies in the Malaysian oil palm estates and palm oil mills towards net-zero emissions.

Malaysia is the second largest producer and exporter of palm oil. Though several works have explored achieving emissions reduction in the palm oil sector, there existing gaps in analysing pathways for achieving net-zero emissions. Moreover, there are limited studies that evaluate the potential of palm oil biomass utilisation pathways based on emissions reduction capabilities, the cost of emissions reduction, and the technology readiness for implementation. Therefore, this study analysed decarbonisation pathways for the upstream and midstream segments of the palm oil sector in Malaysia, encompassing oil palm plantations and palm oil mills. Various sources of greenhouse gas emissions in oil palm plantations and palm oil mills were identified and estimates of emissions were determined as theoretical emissions. The current emissions were established based on the current best practice in the plantation and mill. Several biomass conversion technologies for the recovery of palm-based by-products and conversion into value-added products to decarbonise the palm oil sector and evaluated strategies to attain net-zero status are considered. In this work, the analysis considered both the existing technologies that are adopted by plantations and mills as well as the emerging technologies that have scope for implementation. With the proposed approach, the current emissions level for crude palm oil (CPO) production in Malaysia is estimated as 1121.49 kg CO2-eq/t CPO. In current industry practice, empty fruit bunch (EFB) is underutilised as mills are typically located at rural areas with lack of suitable transportation. Besides, the lack of accessibility to the grid also limits the potential of converting EFB into electricity as supply for national grid. This work examined various pathways for EFB utilisation under different scenarios evaluating their contribution potential towards net-zero target in an energy self-sustained CPO production. As shown in the results, converting EFB to briquettes and pellets are able to achieve the net-zero objective. Furthermore, EFB-biochar and EFB-syngas pathways also exhibit the potential to accomplish the net-zero target. Note that this work also assessed the technologies' readiness levels, identified challenges in implementation, and proposed several recommendations.

IFN-γ is essential for alveolar macrophage-driven pulmonary inflammation in macrophage activation syndrome.

Macrophage activation syndrome (MAS) is a life-threatening cytokine storm complicating systemic juvenile idiopathic arthritis (SJIA) driven by IFN-γ. SJIA and MAS are also associated with an unexplained emerging inflammatory lung disease (SJIA-LD), with our recent work supporting pulmonary activation of IFN-γ pathways pathologically linking SJIA-LD and MAS. Our objective was to mechanistically define the potentially novel observation of pulmonary inflammation in the TLR9 mouse model of MAS. In acute MAS, lungs exhibit mild but diffuse CD4-predominant, perivascular interstitial inflammation with elevated IFN-γ, IFN-induced chemokines, and alveolar macrophage (AMϕ) expression of IFN-γ-induced genes. Single-cell RNA sequencing confirmed IFN-driven transcriptional changes across lung cell types with myeloid expansion and detection of MAS-specific macrophage populations. Systemic MAS resolution was associated with increased AMϕ and interstitial lymphocytic infiltration. AMϕ transcriptomic analysis confirmed IFN-γ-induced proinflammatory polarization during acute MAS, which switches toward an antiinflammatory phenotype after systemic MAS resolution. Interestingly, recurrent MAS led to increased alveolar inflammation and lung injury, and it reset AMϕ polarization toward a proinflammatory state. Furthermore, in mice bearing macrophages insensitive to IFN-γ, both systemic features of MAS and pulmonary inflammation were attenuated. These findings demonstrate that experimental MAS induces IFN-γ-driven pulmonary inflammation replicating key features of SJIA-LD and provides a model system for testing potentially novel treatments directed toward SJIA-LD.

Safety and health risk assessment methodology of dermal and inhalation exposure to formulated products ingredients.

Consumers are commonly exposed to numerous chemical ingredients found in various formulated products especially household and personal care products. Therefore, identification of hazardous ingredients contained in those products should be performed at the early stages of product design to reduce the high cost of redesigning the products at the final stage. Thus, a systematic safety and health risk assessment methodology is required for the product formulation design. In this work, a two-step index-based methodology is presented to estimate the severity of the hazards and the magnitude of risks. In Tier 1 assessment, potential hazards of the ingredients were identified by following the Product Ingredient Safety Index (PISI). The basic toxicology information of ingredients was required for this assessment. In Tier 2 assessment, the extent of risks of the ingredients via dermal and inhalation exposure routes were evaluated. At this stage, the concentration of ingredients and the amount of exposure were considered. The value of Margin of Exposure (MOE) was used as an indicator in the development of Product Ingredient Exposure Index (PIEI). To demonstrate the proposed methodology, a case study on the evaluation of potential hazards and the risks from ingredients used in personal care product formulations were performed.

When not to start antibiotics: avoiding antibiotic overuse in the intensive care unit.

BACKGROUND: Most intensive care unit (ICU) patients receive broad-spectrum antibiotics. While lifesaving in some, in others these treatments may be unnecessary and place patients at risk of antibiotic-associated harms. OBJECTIVES: To review the literature exploring how we diagnose infection in patients in the ICU and address the safety and utility of a 'watchful waiting' approach to antibiotic initiation with selected patients in the ICU. SOURCES: A semi-structured search of PubMed and Cochrane Library databases for articles published in English during the past 15 years was conducted. CONTENT: Distinguishing infection from non-infectious mimics in ICU patients is uniquely challenging. At present, we do not have access to a rapid point-of-care test that reliably differentiates between individuals who need antibiotics and those who do not. A small number of studies have attempted to compare early aggressive versus conservative antimicrobial strategies in the ICU. However, this body of literature is small and not robust enough to guide practice. IMPLICATIONS: This issue will not likely be resolved until there are diagnostic tests that rapidly and reliably identify the presence or absence of infection in the ICU population. In the meantime, prospective trials that identify clinical situations wherein it is safe to delay or withhold antibiotic initiation in the ICU until the presence of an infection is proven are warranted.

Design, optimisation and reliability allocation for energy systems based on equipment function and operating capacity.

Designers of energy systems often face challenges in balancing the trade-off between cost and reliability. In literature, several papers have presented mathematical models for optimizing the reliability and cost of energy systems. However, the previous models only addressed reliability implicitly, i.e., based on availability and maintenance planning. Others focused on allocation of reliability based on individual equipment requirements via non-linear models that require high computational effort. This work proposes a novel mixed-integer linear programming (MILP) model that combines the use of both input-output (I-O) modelling and linearized parallel system reliability expressions. The proposed MILP model can optimize the design and reliability of energy systems based on equipment function and operating capacity. The model allocates equipment with sufficient reliability to meet system functional requirements and determines the required capacity. A simple pedagogical example is presented in this work to illustrate the features of proposed MILP model. The MILP model is then applied to a polygeneration case study consisting of two scenarios. In the first scenario, the polygeneration system was optimized based on specified reliability requirements. The technologies chosen for Scenario 1 were the CHP module, reverse osmosis unit and vapour compression chiller. The total annualized cost (TAC) for Scenario 1 was 53.3 US$ million/year. In the second scenario, the minimum reliability level for heat production was increased. The corresponding results indicated that an additional auxiliary boiler must be operated to meet the new requirements. The resulting TAC for the Scenario 2 was 5.3% higher than in the first scenario.

Emergency nurses' knowledge and understanding of their role in recognising and responding to patients with sepsis: A qualitative study.

AIM: Sepsis is a significant and time-sensitive clinical concern for patients who present to Emergency Departments (EDs). Existing guidelines do not define nurses' roles in managing sepsis. This study explored ED nurses' experiences and perceptions around recognising and responding to patients with sepsis, and their awareness of sepsis screening and prognostic tools. The knowledge and insights gained from this study may be used to inform local and international ED policies, and enrich nursing educational packages that may be used to improve quality of patient care and patient outcomes. METHODS: Qualitative design incorporating semi-structured interviews with 14 ED nurses was undertaken. Thematic and consensus-based content analyses were used to explore transcripts. FINDINGS: Six key themes were identified; (1) contribution of the organisation, (2) appreciation of knowledge, (3) appreciation of clinical urgency, (4) appreciation of importance of staff supervision, (5) awareness of the importance of staff experience, and (6) awareness of the need to seek advice. CONCLUSION: ED nurses' identified deficits in their capacity to recognise and respond to patients with sepsis, despite their vital role within the multidisciplinary team that cares for patients with sepsis. The knowledge and insights gained from this study can be used to inform ED policies, to enrich context-specific educational packages that aim to improve quality of patient care and outcomes and identify areas for further research. Development and implementation of a nurse-inclusive sepsis pathway may address many deficits identified in this study.

Experimental validation of robot-assisted cardiovascular catheterization: model-based versus model-free control.

PURPOSE: In cardiac electrophysiology, a long and flexible catheter is delivered to a cardiac chamber for the treatment of arrhythmias. Although several robot-assisted platforms have been commercialized, the disorientation in tele-operation is still not well solved. We propose a validation platform for robot-assisted cardiac EP catheterization, integrating a customized MR Safe robot, a standard clinically used EP catheter, and a human-robot interface. Both model-based and model-free control methods are implemented in the platform for quantitative evaluation and comparison. METHODS: The model-based and model-free control methods were validated by subject test (ten participants), in which the subjects have to perform a simulated radiofrequency ablation task using both methods. A virtual endoscopic view of the catheter is also provided to enhance hand-to-eye coordination. Assessment indices for targeting accuracy and efficiency were acquired for the evaluation. RESULTS: (1) Accuracy: The average distance measured from catheter tip to the closest lesion target during ablation of model-free method was 19.1% shorter than that of model-based control. (2) Efficiency: The model-free control reduced the total missed targets by 35.8% and the maximum continuously missed targets by 46.2%, both indices corresponded to a low p value ([Formula: see text]). CONCLUSION: The model-free method performed better in terms of both accuracy and efficiency, indicating the model-free control could adapt to soft interaction with environment, as compared with the model-based control that does not consider contacts.

Nonparametric Online Learning Control for Soft Continuum Robot: An Enabling Technique for Effective Endoscopic Navigation.

Bioinspired robotic structures comprising soft actuation units have attracted increasing research interest. Taking advantage of its inherent compliance, soft robots can assure safe interaction with external environments, provided that precise and effective manipulation could be achieved. Endoscopy is a typical application. However, previous model-based control approaches often require simplified geometric assumptions on the soft manipulator, but which could be very inaccurate in the presence of unmodeled external interaction forces. In this study, we propose a generic control framework based on nonparametric and online, as well as local, training to learn the inverse model directly, without prior knowledge of the robot's structural parameters. Detailed experimental evaluation was conducted on a soft robot prototype with control redundancy, performing trajectory tracking in dynamically constrained environments. Advanced element formulation of finite element analysis is employed to initialize the control policy, hence eliminating the need for random exploration in the robot's workspace. The proposed control framework enabled a soft fluid-driven continuum robot to follow a 3D trajectory precisely, even under dynamic external disturbance. Such enhanced control accuracy and adaptability would facilitate effective endoscopic navigation in complex and changing environments.

Cost awareness among healthcare professionals at a South African hospital: A cross-sectional survey.

BACKGROUND: Financial cost is a recognised cause of lack of access to adequate healthcare in South Africa (SA). Data describing the SA healthcare professional (HCP)'s awareness of costs are scant. Their increased awareness of healthcare costs may improve efficacy and reduce wasteful expenditure. OBJECTIVE: To assess SA HCP's knowledge of healthcare costs, identify factors that influence cost awareness, and to determine if surveyed HCPs received training related to cost management during their studies or at any stage during their practice. METHODS: This cross-sectional survey was conducted by means of a standardised questionnaire. HCPs working at a major tertiary academic hospital were asked to answer an anonymous standardised questionnaire aimed at determining their awareness of the costs of commonly requested hospital items and tests. Cost accuracy was determined by assessing the log deviation of the estimated cost from true cost, with values >0 and <0 representing overestimates and underestimates, respectively. Cost estimations were considered correct if the absolute value of the log deviation was <0.2. Participants' attitudes towards the potential impact of the availability of cost information on their practice were assessed. RESULTS: The overall cost estimation of accuracy was low (mean 0.60; standard deviation 1.99) and differed widely between items. Cheaper items were more likely to be overestimated and expensive items to be underestimated. The majority of participants indicated that cost awareness education was not part of their training or practice (84.5%) and that they would like cost information to be made readily available (92.2%). Eighty-four percent of participants were of the opinion that cost information would not negatively affect patient care. CONCLUSION: The use of percentage deviation from true cost as a method of assessing cost awareness creates a bias towards overestimation, which is more relevant for cheap items, as larger overestimates are more common for these items. We propose the use of log deviation of the estimated cost from the true cost as a method of assessing cost estimation accuracy. HCPs have a limited understanding of the costs of disposables, tests and drugs commonly used in their practice and would prefer that cost information be made readily available to them. Attention should be paid to improving cost awareness among HCPs working at SA hospitals.

Avatar - a multi-sensory system for real time body position monitoring.

Virtual reality and computer assisted physical rehabilitation applications require an unobtrusive and inexpensive real time monitoring systems. Existing systems are usually complex and expensive and based on infrared monitoring. In this paper we propose Avatar, a hybrid system consisting of off-the-shelf components and sensors. Absolute positioning of a few reference points is determined using infrared diode on subject's body and a set of Wii Remotes as optical sensors. Individual body segments are monitored by intelligent inertial sensor nodes iSense. A network of inertial nodes is controlled by a master node that serves as a gateway for communication with a capture device. Each sensor features a 3D accelerometer and a 2 axis gyroscope. Avatar system is used for control of avatars in Virtual Reality applications, but could be used in a variety of augmented reality, gaming, and computer assisted physical rehabilitation applications.

Analysing the relationship between voter turnout and health in Ireland.

Health issues are an integral part of the political agenda in Ireland. Yet no study to date has examined the impact of health concerns on political outcomes. This study investigates the relationship between health, both physical and psychological, and perceptions of the health service, and voter turnout in Ireland using the European Social Survey in 2005, (n = 2286, RR 59.7%). The results show that individuals with poor subjective health are significantly less likely to vote in a General Election. Dissatisfaction with the health service is also associated with a lower probability of voting. However these effects interact: those with poor health and who are dissatisfied with the health service are more likely to vote. Psychological well-being has no effect on voter turnout. The health effects identified in this study are large and further work is needed in this area to identify the causal mechanisms underlying this relationship.

Distinct transcriptional control and action of fibroblast growth factor receptor 4 in differentiating skeletal muscle cells.

Although FGF signaling promotes myoblast proliferation and represses myogenic differentiation, one of the FGF receptors (FGFR), FGFR4, is expressed mainly in mature skeletal muscle. Disruption of FGFR4 signaling interrupts chick limb muscle formation. To determine the developmental regulation of FGFR4 expression, we compared the transcriptional control and action of FGFR4 in myoblasts and myotubes. We identified higher FGFR4 expression in differentiated myotubes than precursor myoblasts. FGFR4 promoter activity was localized within a region 115 bp upstream of the transcription start site. Overlapping fragments of this promoter displayed a distinct difference when compared by electromobility shift assay (EMSA) using nuclear extracts from myoblasts and myotubes. While fragments B (-95/-56) and C (-65/-26) formed specific complexes in both cell types, these complexes were consistently more intense in myotubes than myoblasts. These complexes were efficiently competed by an Sp-type oligonucleotide and were supershifted by Sp1 and by Sp3 antibodies. Deletions of the Sp-binding sites in fragment B (-95/-56) confirmed their critical contribution to promoter activity. Moreover, Sp1 expression correlated with FGFR4-expression in myotubes. To determine whether FGFR4 expression regulates myoblast differentiation, we infected a soluble dominant-negative FGFR4-containing adenovirus into these cells. This significantly impeded Erk1/2 phosphorylation and differentiation of myoblasts into MHC-expressing myotubes. Our findings point to distinct transcriptional regulation and action for FGFR4 in differentiating skeletal muscle cells.

Overexpression of the endoplasmic reticulum 60 protein ER-60 downregulates apoB100 secretion by inducing its intracellular degradation via a nonproteasomal pathway: evidence for an ER-60-mediated and pCMB-sensitive intracellular degradative pathway.

Co- and posttranslational regulation of apolipoprotein B (apoB) has been postulated to involve degradation by both proteasomal and nonproteasomal pathways; however, nonproteasomal mechanisms of apoB degradation are currently unknown. We have previously demonstrated an intracellular association of newly synthesized apoB with endoplasmic reticulum (ER)-60, an ER-localized protein, possessing both proteolytic and chaperone activities. In the present paper, adenoviral expression vectors containing rat ER-60 cDNA were used to achieve dose- and time-dependent overexpression of ER-60 to investigate its role in apoB100 turnover. Overexpressed ER-60 accumulated in the microsomal lumen of HepG2 cells and was associated with apoB100 in dense lipoprotein particles. Overexpression of ER-60 in HepG2 cells significantly reduced both intracellular and secreted apoB100, with no effect on the secretion of a control protein, albumin. Similar results were obtained in McA-RH7777 rat hepatoma cells. ER-60-stimulated apoB100 degradation and inhibition of apoB100 secretion were sensitive to the protease inhibitor, p-chloromercuribenzoate (pCMB), in a dose-dependent manner but were unaffected by the proteasomal or lysosomal protease inhibitors, N-acetyl-leucinyl-leucinyl-nor-leucinal, E64, and leupeptin. Interestingly, enhanced expression of ER-60 induced apoB100 fragmentation in permeabilized HepG2 cells and resulted in detection of a unique 50 kDa degradation intermediate, a process that could be inhibited by pCMB. Intracellular stability and secretion of apoB100 in primary hamster hepatocytes were also found to be sensitive to pCMB. When taken together, the data suggest an important role for ER-60 in promoting apoB100 degradation via a pCMB-sensitive process in the ER. ER-60 may act directly as a protease or may be involved indirectly as a chaperone/protein factor targeting apoB100 to this nonproteasomal and pCMB-sensitive degradative pathway.

Expression of human hepatic lipase in the rabbit model preferentially enhances the clearance of triglyceride-enriched versus native high-density lipoprotein apolipoprotein A-I.

BACKGROUND: We have shown previously that triglyceride (TG) enrichment of HDL, as occurs in hypertriglyceridemic states, contributes to HDL lowering in humans by enhancing the clearance of HDL apolipoprotein (apo) A-I from the circulation. In the New Zealand White rabbit, an animal naturally deficient in hepatic lipase (HL), we demonstrated that TG enrichment of HDL per se is not sufficient to enhance HDL clearance in the absence of ex vivo lipolysis by HL. Here, we examined in the rabbit the interaction between in vivo HL lipolytic action and HDL TG enrichment on the subsequent metabolic clearance of HDL apoA-I. METHODS AND RESULTS: The clearance of HDL, TG-enriched with human VLDL (12% mass TG), was compared with a simultaneously injected native rabbit HDL tracer (8% TG) 5 to 7 days after injection of recombinant (r) adenovirus expressing either the human HL or lacZ transgene (n=6 animals each). In rHL-Adv rabbits, HL activity levels were 2- to 7-fold higher (versus rlacZ-Adv controls; P<0.01), and there were significant (P<0.05) reductions in HDL TG (-18%), cholesterol (-21%), cholesteryl ester (-24%), and phospholipid (-14%). Moreover, the clearance of TG-enriched versus native HDL was significantly greater (by 50%; 0.122+/-0.022 versus 0.081+/-0.015 pools/h; P<0.01) in rHL-Adv rabbits but not in controls. CONCLUSIONS: These studies have shown that TG enrichment of HDL in the presence but not in the absence of in vivo expression of moderate levels of lipolytically active HL results in enhanced HDL clearance, demonstrating the important interaction between TG enrichment and HL action in the pathogenesis of HDL lowering in hypertriglyceridemic states.

Therapeutic monitoring of sirolimus: its contribution to optimal prescription.

It is now common practice to measure immunosuppressive drugs in blood as a guide to therapy. The immunosuppressive drug sirolimus, recently approved for use following kidney transplantation, was developed in the context of this clinical approach. Throughout the early clinical studies, validated analytical techniques based on chromatographic techniques were used to measure the drug. After a brief period in which an immunoassay was available, routine measurements are again being performed by chromatographic assays. In this article the use of blood concentration measurements in the assessment of the early and pivotal clinical trials of the drug is documented. Then, the rationale for the routine monitoring of the drug in clinical practice, a regulatory requirement in some countries, is set out. It is concluded that the development of this compound has benefited from experience gained during the pharmacokinetic assessment of other immunosuppressive drugs. The pharmacokinetic data accumulated on sirolimus have been a key element in formulating guidelines on dosing with this drug, both when used in combination with cyclosporine and when used after cyclosporine withdrawal.

Pax-6 activates endogenous proglucagon gene expression in the rodent gastrointestinal epithelium.

The proglucagon gene encodes pancreatic glucagon and the glucagon-like peptides, which exert diverse effects on nutrient absorption and assimilation. The therapeutic potential of glucagon-like peptide-1 (GLP-1) has fostered interest in development of cellular engineering approaches to augment endogenous intestinal-derived GLP-1 for the treatment of type 2 diabetes. We have used adenovirus technology to examine the potential roles of the transcription factors Cdx-2/3 and Pax-6 as activators of endogenous proglucagon gene expression in enteroendocrine cell lines and in nontransformed rat intestinal cells. Adenoviral-expressed Cdx-2/3 and Pax-6 activated proglucagon promoter-luciferase activity in baby hamster kidney (BHK) fibroblasts, HEK 293 cells, and enteroendocrine cell lines. Pax-6, but not Cdx-2/3, induced expression of the endogenous proglucagon gene in enteroendocrine cell lines, but not in heterologous fibroblasts. Furthermore, transduction of primary rat intestinal cell cultures in vitro, or the rat colonic epithelium in vivo, with Ad-Pax-6 activated endogenous proglucagon gene expression. These data demonstrate that Pax-6, but not Cdx-2/3, is capable of activating the endogenous proglucagon gene in both immortalized enteroendocrine cells and the nontransformed intestinal epithelium in vivo.

Lack of effects of nose-only inhalation exposure on testicular toxicity in male rats.

Reductions in testicular mass, sperm motility, and mating frequency have been attributed to the stresses caused by confinement of Sprague-Dawley male rats in nose-only inhalation exposure tubes. Testicular changes, including an increase in testicular atrophy, have been detected at an increased incidence in male rats used in inhalation studies as compared with rats of the same age and strain used in oral toxicity studies. This study was designed to determine whether nose-only exposure of male rats caused testicular toxicity under conditions of cooling of the exposure room and appropriate acclimation to the exposure tubes. In order to acclimate the rats to the nose-only inhalation exposure apparatus, all male rats were placed in the exposure tubes for at least four successively increasing time intervals (15, 30, 45, and 60 min) on 4 separate days, with a rest period of approximately 48 h between the first and second acclimation. Twenty male rats were exposed nose-only to filtered air for approximately 2 h per day for 28 days before cohabitation and continuing throughout a 14-day cohabitation period. To reduce thermal stress, the exposure room temperature was maintained at 64 to 70 degrees F. Twenty control rats were housed in the same room as the exposed rats but were not placed in exposure tubes. End points monitored were body weight, testicular weight, sperm count, sperm motility, and histopathology of the testes, epididymides, prostate, and seminal vesicles. The control rats gained weight more rapidly than the exposed rats. All the rats in both groups mated successfully, and testicular weights, normalized to body weight, were similar for both groups. More importantly, there were no microscopic changes that could be considered an adverse effect on the reproductive tissues in the male rats placed in exposure tubes. Thus, nose-only exposure for up to 2 h per day for a total of 42 days did not cause adverse effects on the reproductive organs, fertility, or reproductive performance of male rats under the conditions of this study.

Developmental toxicity study of mangafodipir trisodium injection (MnDPDP) in New Zealand white rabbits.

Mangafodipir trisodium injection (MnDPDP) is an intravenously administered manganese chelate undergoing clinical evaluation for magnetic resonance imaging contrast enhancement of the hepatobiliary system. The anticipated single clinical dose for adults is 5 micromol/kg body wt. MnDPDP, as well as the inorganic salt, MnCl2, was previously shown to induce a specific syndrome of skeletal abnormalities in rats. The syndrome malformations included angulated or irregularly shaped clavicle, femur, fibula, humerus, ilium, radius, scapula, tibia, and/or ulna. The objective of the present study was to assess the developmental toxicity of MnDPDP in a second mammalian species, the New Zealand White rabbit. MnDPDP was intravenously administered daily to groups of rabbits (22 per group) on Days 6 through 18 of pregnancy at doses of 0 (saline), 5, 20, 40, and 60 micromol/kg MnDPDP. Fetuses were examined on Day 29 of pregnancy for external, visceral, and skeletal abnormalities. Treatment with MnDPDP did not result in overt symptoms of maternal toxicity, and there were no significant effects on maternal body weight gains or feed consumption. The maternal no-observed-adverse-effect level (NOAEL), therefore, was 60 micromol/kg MnDPDP. Treatment with MnDPDP resulted in a significant increase in postimplantation loss at 60 micromol/kg, but there was no significant increase in external, visceral, or skeletal abnormalities at any dose. The developmental NOAEL for MnDPDP, therefore, was 40 micromol/kg. These results indicate that the developmental toxicity profile of MnDPDP differs considerably in the rat and rabbit. In the rat, this compound induces specific skeletal abnormalities, whereas in the rabbit, embryo/fetal toxicity is the most sensitive developmental endpoint with no evidence for the induction of specific skeletal abnormalities.