Exploring multiple stressor effects with Ecopath, Ecosim, and Ecospace: Research designs, modeling techniques, and future directions.

Understanding the cumulative effects of multiple stressors is a research priority in environmental science. Ecological models are a key component of tackling this challenge because they can simulate interactions between the components of an ecosystem. Here, we ask, how has the popular modeling platform Ecopath with Ecosim (EwE) been used to model human impacts related to climate change, land and sea use, pollution, and invasive species? We conducted a literature review encompassing 166 studies covering stressors other than fishing mostly in aquatic ecosystems. The most modeled stressors were physical climate change (60 studies), species introductions (22), habitat loss (21), and eutrophication (20), using a range of modeling techniques. Despite this comprehensive coverage, we identified four gaps that must be filled to harness the potential of EwE for studying multiple stressor effects. First, only 12% of studies investigated three or more stressors, with most studies focusing on single stressors. Furthermore, many studies modeled only one of many pathways through which each stressor is known to affect ecosystems. Second, various methods have been applied to define environmental response functions representing the effects of single stressors on species groups. These functions can have a large effect on the simulated ecological changes, but best practices for deriving them are yet to emerge. Third, human dimensions of environmental change - except for fisheries - were rarely considered. Fourth, only 3% of studies used statistical research designs that allow attribution of simulated ecosystem changes to stressors' direct effects and interactions, such as factorial (computational) experiments. None made full use of the statistical possibilities that arise when simulations can be repeated many times with controlled changes to the inputs. We argue that all four gaps are feasibly filled by integrating ecological modeling with advances in other subfields of environmental science and in computational statistics.

Forensic genetic genealogy using microarrays for the identification of human remains: The need for good quality samples - A pilot study.

The successful application of forensic genetic genealogy (FGG) to identify Jane and John Doe cases in the United States has raised the prospect of using the technique in Australia to assist in the reconciliation of unidentified human remains (UHRs) with long term missing persons. A study was conducted to explore the feasibility of FGG using whole genome array (WGA) data from both pristine control samples as well as compromised casework samples, with the view to explore how DNA quantity and quality impacted on the ability to generate search results when compared to a genetic genealogy database, such as GEDmatch. From this study, several insights were gained as to the impact DNA quantity and degradation had on the percentage of SNPs genotyped and heterozygote/homozygote ratio - which are critical for successful matching outcomes. It was noted in this study (using a control sample) that successful matching occurred when genotyping errors were 5% or less. Two UHR cases were matched to kits on GEDmatch PRO, which provided investigative leads for identification purposes. The effectiveness of the FGG approach to match casework samples (as well as volunteer samples used in the study) is indicative of the usage of 'direct-to-consumer' (DTC) genetic testing by Australians. Given the (often) limited availability of casework samples, findings from this study will assist Australian agencies considering the use of FGG, to determine if WGA is a suitable method for their application.

Imaging Characteristics of Wingless Pathway Subgroup Medulloblastomas: Results from the German HIT/SIOP-Trial Cohort.

BACKGROUND AND PURPOSE: In addition to the 4 histopathologically defined entities of medulloblastoma, 4 distinct genetically defined subgroups have been included in the World Health Organization classification of 2016. The smallest subgroup is the medulloblastoma with activated wingless pathway. The goal of this study was to identify a typical MR imaging morphology in a larger number of pediatric patients with wingless pathway medulloblastoma. MATERIALS AND METHODS: From January 2001 to October 2017, of 75 patients with histologically confirmed and molecularly subgrouped wingless pathway medulloblastomas recruited to the German Pediatric Brain Tumor (HIT) trials, 38 patients (median age, 12.8 ± 4.6 years at diagnosis; 24 [63.2%] female) had preoperative imaging that passed the entry criteria for this study. Images were rated by the local standardized imaging criteria of the National Reference Center of Neuroradiology. Additionally, a modified laterality score was used to determine tumor localization and extension. RESULTS: Twenty-eight of 38 (73.7%) were primary midline tumors but with a lateral tendency in 39.3%. One extensively eccentric midline tumor was rated by the laterality score as in an off-midline position. Five tumors were found in the cerebellopontine angle; 3, in the deep white matter; and 2, in a cerebellar hemisphere. Leptomeningeal dissemination was rare (11.5%). In 60.5%, intratumoral blood-degradation products were found, and 26.3% showed cysts with blood contents. CONCLUSIONS: According to our observations, wingless pathway medulloblastomas are not preferentially off-midline tumors as postulated in previous studies with smaller wingless pathway medulloblastoma cohorts. Dense intratumoral blood-degradation products and cysts with blood contents are frequently found and might help to differentiate wingless pathway medulloblastoma from other medulloblastoma subtypes.

Anti-IFNAR treatment does not reverse neuropsychiatric disease in MRL/lpr lupus mice.

OBJECTIVE: Many systemic lupus erythematosus patients display a type I interferon (IFN) signature, and IFNα levels positively correlate with disease severity. Previous studies blocking the type I IFN pathway systemically in lupus models showed some beneficial effects. However, its effects on neuropsychiatric manifestations have yet to be carefully assessed, even though IFNα has been associated with induction of depression. Our aim was to investigate whether disrupting the type I IFN pathway would attenuate the development of murine neuropsychiatric lupus. METHODS: Female MRL/lpr mice were administered an antitype I IFN receptor (IFNAR) antibody or a control antibody intraperitoneally three times weekly for 12 weeks starting at age 4-5 weeks. Behavior was assessed during and at the end of the treatment schedule. RESULTS: No significant differences were seen between the anti-IFNAR- and control-treated mice when assessing for depression-like behavior or cognitive dysfunction, although anti-IFNAR antibody-treated mice displayed significant decreases in levels of IFN-stimulated genes. Anti-IFNAR treatment also did not significantly improve brain histology, cellular infiltration, or blood-brain barrier integrity. CONCLUSIONS: Surprisingly, our results showed no improvement in neuropsychiatric disease and suggest that the role of IFNAR signaling in the pathogenesis of neuropsychiatric lupus continues to need to be carefully assessed.

ADHD patients fail to maintain task goals in face of subliminally and consciously induced cognitive conflicts.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) patients have been reported to display deficits in action control processes. While it is known that subliminally and consciously induced conflicts interact and conjointly modulate action control in healthy subjects, this has never been investigated for ADHD. METHOD: We investigated the (potential) interaction of subliminally and consciously triggered response conflicts in children with ADHD and matched healthy controls using neuropsychological methods (event-related potentials; ERPs) to identify the involved cognitive sub-processes. RESULTS: Unlike healthy controls, ADHD patients showed no interaction of subliminally and consciously triggered response conflicts. Instead, they only showed additive effects as their behavioural performance (accuracy) was equally impaired by each conflict and they showed no signs of task-goal shielding even in cases of low conflict load. Of note, this difference between ADHD and controls was not rooted in early bottom-up attentional stimulus processing as reflected by the P1 and N1 ERPs. Instead, ADHD showed either no or reversed modulations of conflict-related processes and response selection as reflected by the N2 and P3 ERPs. CONCLUSION: There are fundamental differences in the architecture of cognitive control which might be of use for future diagnostic procedures. Unlike healthy controls, ADHD patients do not seem to be endowed with a threshold which allows them to maintain high behavioural performance in the face of low conflict load. ADHD patients seem to lack sufficient top-down attentional resources to maintain correct response selection in the face of conflicts by shielding the response selection process from response tendencies evoked by any kind of distractor.

Predictors of Impaired Postpartum Renal Function in Women after Preeclampsia: Results of a Prospective Single Center Study.

Objective. The purpose of this prospective study was to investigate the predictive value of single prepartum findings combined with serum biomarkers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor) indicating severity of preeclampsia (PE) for occurrence and extent of impaired postpartum kidney function. Study Design. In this prospective, single center study 44 PE patients were compared to 39 healthy controls (similar in age and gestational age with singleton pregnancy) evaluated at time of delivery and at 6 months and 12 months postpartum. p values below 0.05 are considered statistically significant. Results. The majority of the PE patients had persistence of proteinuria (>120 mg/L after delivery) 6 months (p = 0.02) and 12 months postpartum (p < 0.0001) compared to controls. Also reduced GFR (glomerular filtration rate) persisted up to 6 months postpartum in PE patients compared to controls (p < 0.001). Prepartum sFlt-1 levels indeed correlated with impaired renal function parameters. Conclusion. A significant proportion of our PE patients had lower GFR levels and persistent proteinuria up to 12 months postpartum. Prepartum sFlt-1 is a trend-setting marker for impaired renal function postpartum, but it is not sufficient enough to predict renal impairment after PE. An evaluation of 24-month follow-up data is scheduled.

[Symptomatic calcification of the lateral collateral knee ligament]. / Symptomatische Verkalkung des lateralen Kniegelenkkollateralligaments.

We describe a case of symptomatic calcification of the lateral collateral knee ligament in a 53-year-old female patient. The calcification became extremely painful and increased in size and it was decided to resect the calcification operatively because of pain progression. After operative resection of the deposits the patient is currently free of complaints and relapse-free after 4.5 years. In the literature four cases of calcification of the medial collateral ligament are described which were also successfully treated by operative resection.

Personal carbon monoxide exposures among firefighters at prescribed forest burns in the Southeastern United States.

Exposure to combustion products from wildland fires causes respiratory irritation and decreased lung function among firefighters. The authors evaluated carbon monoxide (CO) exposures of a group of wildland firefighters who conducted prescribed burns in the southeastern United States of America. A total of 149 person-days of samples were collected using data logging CO monitors. A questionnaire was administered to collect data on job tasks and self-reported smoke exposure. Overall, the highest exposures were seen amongst firefighters assigned to holding and mop-up tasks (geometric mean [GM]: 2.6 ppm), whereas the lowest were associated with lighting and jobs such as burn boss (GM: 1.6 and 0.3 ppm, respectively). The self-reported smoke exposure showed a significant linear trend with increasing CO exposure. The numbers of acres burned or burn duration, however, were not good predictors of exposure.

Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model.

Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer's disease (AD). We utilized several mammalian cellular models to determine whether LAT regulates mammalian target of rapamycin (mTOR) and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of Aß42 and α-synuclein. We conclude that LAT possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and behavior might warranty the further study of LAT as a potentially viable lead compound that might yield more consistent clinical benefit following the optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive activities.

Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain.

Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated with enhanced cognition, neuroprotection and neurogenesis in laboratory animals, and has entered phase II clinical trials for both Alzheimer's disease and Huntington's disease (HD). Based on recent indications that latrepirdine protects cells against cytotoxicity associated with expression of aggregatable neurodegeneration-related proteins, including Aß42 and γ-synuclein, we sought to determine whether latrepirdine offers protection to Saccharomyces cerevisiae. We utilized separate and parallel expression in yeast of several neurodegeneration-related proteins, including α-synuclein (α-syn), the amyotrophic lateral sclerosis-associated genes TDP43 and FUS, and the HD-associated protein huntingtin with a 103 copy-polyglutamine expansion (HTT gene; htt-103Q). Latrepirdine effects on α-syn clearance and toxicity were also measured following treatment of SH-SY5Y cells or chronic treatment of wild-type mice. Latrepirdine only protected yeast against the cytotoxicity associated with α-syn, and this appeared to occur via induction of autophagy. We further report that latrepirdine stimulated the degradation of α-syn in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers of autophagic activity. Ongoing experiments will determine the utility of latrepirdine to abrogate α-syn accumulation in transgenic mouse models of α-syn neuropathology. We propose that latrepirdine may represent a novel scaffold for discovery of robust pro-autophagic/anti-neurodegeneration compounds, which might yield clinical benefit for synucleinopathies including Parkinson's disease, Lewy body dementia, rapid eye movement (REM) sleep disorder and/or multiple system atrophy, following optimization of its pro-autophagic and pro-neurogenic activities.

The importance of Guthrie cards and other medical samples for the direct matching of disaster victims using DNA profiling.

The identification of disaster victims through the use of DNA analysis is an integral part of any Disaster Victim Identification (DVI) response, regardless of the scale and nature of the disaster. As part of the DVI response to the 2009 Victorian Bushfires Disaster, DNA analysis was performed to assist in the identification of victims through kinship (familial matching to relatives) or direct (self source sample) matching of DNA profiles. Although most of the DNA identifications achieved were to reference samples from relatives, there were a number of DNA identifications (12) made through direct matching. Guthrie cards, which have been collected in Australia over the past 30 years, were used to provide direct reference samples. Of the 236 ante-mortem (AM) samples received, 21 were Guthrie cards and one was a biopsy specimen; all yielding complete DNA profiles when genotyped. This publication describes the use of such Biobanks and medical specimens as a sample source for the recovery of good quality DNA for comparisons to post-mortem (PM) samples.

Examples of kinship analysis where Profiler Plus™ was not discriminatory enough for the identification of victims using DNA identification.

The identification of the victims of the 2009 Victorian bushfires disaster, as in other mass disasters, relied on a number of scientific disciplines - including DNA analysis. As part of the DVI response, DNA analysis was performed to assist in the identification of victims through kinship (familial matching to relatives) or direct (self source of sample) matching of DNA profiles. The majority of the DNA identifications made (82%) were achieved through kinship matching of familial reference samples to post mortem (PM) samples obtained from the victims. Although each location affected by the bushfires could be treated as a mini-disaster (having a small closed-set of victims), with many such sites spread over vast areas, DNA analysis requires that the short tandem repeat (STR) system used be able to afford enough discrimination between all the DVI cases to assign a match. This publication highlights that although a 9-loci multiplex was sufficient for a DVI of this nature, there were instances that brought to light the short comings of using a 9-loci multiplex for kinship matching--particularly where multiple family members are victims. Moreso it serves to reinforce the recommendation that a minimum of 12 autosomal STR markers (plus Amelogenin) be used for DNA identification of victims which relies heavily on kinship matching.

Mutualism variation in the nodulation response to nitrate.

The evolution of mutualisms under novel selective pressures will play a key role in ecosystem responses to environmental change. Because fixed nitrogen is traded in plant­rhizobium mutualisms, increasing N availability in the soil is predicted to alter coevolution of these interactions. Legumes typically decrease the number of associations (nodules) with rhizobia in response to nitrate, but the evolutionary dynamics of this response remain unknown. We grew plant and rhizobium genotype combinations in three N environments to assess the coevolutionary potential of the nodule nitrate response in natural communities of plants and rhizobia. We found evidence for coevolutionary genetic variation for nodulation in response to nitrate (G × G × E interaction), suggesting that the mutualism response to N deposition will depend on the combination of partner genotypes. Thus, the nitrate response is not a fixed mechanism in plant­rhizobium symbioses, but instead is potentially subject to natural selection and dynamic coevolution.

Biological monitoring of smoke exposure among wildland firefighters: a pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particular matter, and levoglucosan.

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service-Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM(2.5)) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701+/-95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n=9). PM(2.5) and CO exposures were not significantly correlated, and LG and PM(2.5) exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.

Are women from high-risk ethnic minority groups more likely to decline antenatal HIV screening?

Eight new cases of human immunodeficiency virus (HIV) were diagnosed in the antenatal population of Milton Keynes within the first two years of our 'opt-out' antenatal testing scheme; the majority (6/8) occurred in women of black African origin. Since it is suggested that individuals from high-risk groups are more likely to decline HIV testing, we were concerned that women from this high-risk ethnic group might not be accepting testing. Such a situation would increase the risk of undiagnosed HIV-positive women delivering at Milton Keynes and undermine the potential benefits of the screening programme. Retrospective review of pregnant women delivering in our area over six months was performed. Hospital obstetric and microbiology databases were analysed for results of HIV screening and ethnic origin of patients. A total of 1586 women delivered during the study period. Among the black African women 13/158 (8.2%) declined screening, compared with 120/1214 (9.8%) and 15/153 (9.8%) of white and Asian women, respectively. The high uptake of testing across all groups suggests that the policy of offering and recommending HIV screening to all women is being appropriately implemented. Black African women were more likely to have undergone screening than white or Asian women, although the differences were not statistically significant.

Impact of the acid flow rate on dentin erosion.

OBJECTIVE: The study aimed to evaluate the erosive effects of acids flowing with different velocities and duration on dentin previously pre-treated with distilled water or human saliva. METHODS: Bovine dentin surfaces were submitted to a 10 min demineralisation with hydrochloric or citric acid (pH 2.3, 37 degrees C) in an artificial mouth at flow rates of 3, 2.25, 1.5, 0.75 or 0.15 ml/min or in 30 ml of the respective acid without movement (each subgroup n=16 specimens). Prior to the demineralisation, half of the specimens of each group were either pre-treated with distilled water or human saliva for 120 min. After 2, 5 and 10 min demineralisation, profilometric traces of dentin loss were performed perpendicular to the direction of acid flow at three sites (A-C) with intervals of 500 microm. The first profile (A) was taken in a distance of 1.5 mm from the acid starting to flow over the sample. Thus, median dentin loss at each site was calculated and statistically analysed by five-way ANOVA. RESULTS: Dentin loss increased with increasing acid flow rate and demineralisation time and was higher for demineralisation with citric acid compared to hydrochloric acid. For given flow rates of 0.15 to 3 ml/min, measurement of dentin loss yielded highest values for site A and decreasing values for sites B and C. For all groups, no significant differences of dentin loss were observed between specimens pre-treated with distilled water or human saliva. CONCLUSION: Under the conditions of this study, both duration of demineralisation and acid flow rate but not pre-treatment with distilled water or saliva influence the extent of dentin erosion.

Storm-related carbon monoxide poisoning: lessons learned from recent epidemics.

Over the past 15 years, a number of epidemics of carbon monoxide (CO) poisoning related to various storms have been reported. While the geographical location of these outbreaks and the types of storms involved has been diverse, review of the events reveals a number of common factors and themes. This paper summarizes the details of 9 published reports describing CO poisoning associated with 11 different storms. When common patterns were examined, five "lessons to be learned" from the experience were derived. They are (1) loss of electrical power can lead indirectly to carbon monoxide poisoning, (2) campaigns to educate the public about risks for CO exposure should be timed regionally to coincide with the peak risk for typical storms, (3) significant opportunities exist for prevention of generator-related CO poisoning, (4) there is a window of time for effective communications regarding the dangers of CO poisoning even after a storm strikes, and (5) the major sources of CO responsible for poisonings can be related to the type of storm and are predictable. It is hoped that each of these lessons are used to develop public programs designed to prevent storm-associated CO poisoning in the future.

Human cytomegalovirus persists in myeloid progenitors and is passed to the myeloid progeny in a latent form.

CD34+ progenitor cells can harbour latent human cytomegalovirus (HCMV); however, the mechanisms of HCMV latency remain unclear. We have investigated the effects of the haematopoietic lineage restriction on the establishment and spread of the latent HCMV to progeny cells. In vitro-infected and latently-infected haematopoietic progenitor cells derived from HCMV seropositive donors were studied. The presence of HCMV DNA in bone marrow progenitor (BMP) cells was determined by single colony polymerase chain reaction and fluorescent in situ hybridization (FISH). The presence of CMV DNA was found to be restricted to myeloid progenitors and the percentage of HCMV-infected cells was lower in naturally-infected cells than in in vitro-infected cells. Erythroid differentiation resulted in an abortive infection with persistence of the viral nucleic acids in red cell precursors. In BMP cells from HCMV seronegative donors, HCMV DNA was localized in the nucleus. Bone marrow progenitors in the presence of granulocyte-macrophage colony stimulating factor (GMCSF) maintained HCMV DNA for extended periods of time. No viral production could be detected throughout the culture but the comparison of the numbers of latently-infected cells prior to and after the culture suggests that proliferation of haematopoietic progenitor cells may lead to the expansion of latently-infected cells.