Loss Events Research Articles

Neuroprotective effect of chlorogenic acid on Parkinson's disease like symptoms through boosting the autophagy in zebrafish

Parkinson’s disease (PD) is characterized by both motor and non-motor symptoms, including hypokinesia, postural instability, dopaminergic (DA) neurons loss, and α-synuclein (α-syn) accumulation. A growing number of patients show negative responses towards the current therapies. Thus, preventative or disease-modifying treatment agents are worth to further research. In recent years, compounds extracted from natural sources become promising candidates to treat PD. Chlorogenic acid (CGA) is a phenolic compound appearing in coffee, honeysuckle, and eucommia that showed their potential as antioxidants and neuroprotectors. In this study, we investigated the anti-PD activity of CGA by testing its effect on 1-methyl-4-phenyl-1-1,2,3,6-tetrahydropyridine (MPTP) zebrafish model of PD. It was shown that CGA relieved MPTP-induced PD-like symptoms including DA neurons and blood vessel loss, locomotion reduction, and apoptosis events in brain. Moreover, CGA modulated the expression of PD- and autophagy-related genes (α-syn, lc3b, p62, atg5, atg7, and ulk1b), showing its ability to promote the autophagy which was interrupted in the PD pathology. The unblocked effect of CGA on autophagy was further verified in 6-hydroxydopamine (6-OHDA)-modeled SHSY5Y cells. Our findings indicated that CGA might relieve PD by boosting the autophagy in neuronal cells that makes CGA a potential candidate for anti-PD treatment.

Seasonal and interannual variability of the pelagic ecosystem and of the organic carbon budget in the Rhodes Gyre (eastern Mediterranean): influence of winter mixing

Abstract. The Rhodes Gyre is a cyclonic persistent feature of the general circulation of the Levantine Basin in the eastern Mediterranean Sea. Although it is located in the most oligotrophic basin of the Mediterranean Sea, it is a relatively high primary production area due to strong winter nutrient supply associated with the formation of Levantine Intermediate Water. In this study, a 3D coupled hydrodynamic–biogeochemical model (SYMPHONIE/Eco3M-S) was used to characterize the seasonal and interannual variability of the Rhodes Gyre's ecosystem and to estimate an annual organic carbon budget over the 2013–2020 period. Comparisons of model outputs with satellite data and compiled in situ data from cruises and Biogeochemical-Argo floats revealed the ability of the model to reconstruct the main seasonal and spatial biogeochemical dynamics of the Levantine Basin. The model results indicated that during the winter mixing period, phytoplankton first progressively grow sustained by nutrient supply. Then, short episodes of convection driven by heat loss and wind events, favoring nutrient injections, organic carbon export, and inducing light limitation on primary production, alternate with short episodes of phytoplankton growth. The estimate of the annual organic carbon budget indicated that the Rhodes Gyre is an autotrophic area, with a positive net community production in the upper layer (0–150 m) amounting to 31.2 ± 6.9 gCm-2yr-1. Net community production in the upper layer is almost balanced over the 7-year period by physical transfers, (1) via downward export (16.8 ± 6.2 gCm-2yr-1) and (2) through lateral transport towards the surrounding regions (14.1 ± 2.1 gCm-2yr-1). The intermediate layer (150–400 m) also appears to be a source of organic carbon for the surrounding Levantine Sea (7.5 ± 2.8 gCm-2yr-1) mostly through the subduction of Levantine Intermediate Water following winter mixing. The Rhodes Gyre shows high interannual variability with enhanced primary production, net community production, and exports during years marked by intense heat losses and deep mixed layers. However, annual primary production appears to be only partially driven by winter vertical mixing. Based on our results, we can speculate that future increase of temperature and stratification could strongly impact the carbon fluxes in this region.

Research on safety characteristics of heat pipe reactor with semiconductor thermoelectric conversion system

The heat pipe reactor exhibits notable characteristics of inherent safety and a compact configuration, rendering it a favored choice for space and ocean reactor designs. This study focuses on investigating the safety characteristics of the SAIRS-C space heat pipe reactor by employing a self-developed TAPIRS-D code under three selected typical accidents. The obtained results demonstrate that the heat pipe reactor exhibits inherent safety features, enabling it to sustain normal operation even in the event of partial heat pipe failure(2 out of 60 heat pipes fail) and partial heat sink loss(cooling rate decreasing from 100% to 10% in 10 s). The reactivity-insertion accident(0.358$ is introduced into the core) is found to exert the most significant influence on the heat pipe reactor. However, the crucial parameters of the reactor during the accident, such as fuel temperature, remain within the established safety limits. The outcomes of this research not only contribute to a comprehensive understanding of safety characteristics of heat pipe reactor, but also provide a crucial guidance for further design enhancements.

The market reaction to operational risk events in the energy sector

AbstractDespite the growing importance of operational risk, little is known about the impact of operational losses on the stock prices of energy firms. We fill this void by examining the market reaction of energy firms to a unique international sample of 452 operational loss events announced between 1996 and 2021, constructed using the SAS OpRisk Global Data database. Our results reveal negative and significant abnormal returns following the announcement of operational losses, while further analysis shows that results vary with event and/or announcing firm characteristics. Our evidence can help inform multiple stakeholders in the energy industry in the pricing, asset allocation, and risk management functions, as well as help regulators design effective mechanisms to mitigate the impact of operational losses on the economy and society.

Cardiovascular Autonomic Neuropathy and Risk of Kidney Function Decline in Type 1 and Type 2 Diabetes: Findings From the PERL and ACCORD Cohorts.

Previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among persons with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N=469) and with type 2 diabetes (T2D) from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (N=7,973). Baseline CAN was ascertained using ECG-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss ≥-5 ml/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed effect, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 (95%CI [-1.93, -0.37], P= 4.0x10-3) ml/min/1.73m2/year in PERL and 0.34 (95%CI [-0.49, -0.19], P= 6.3x10-6) ml/min/1.73m2/year in ACCORD. This translated in 2.11 (95% CI [1.23-3.63], P=6.9x10-3) and 1.39 (95% CI [1.20-1.61], P=1.1x10-5) odds ratios of rapid kidney function decline in PERL and ACCORD, respectively. Baseline CAN was also associated with a greater risk of ≥40% GFR loss events during follow-up (HR=2.60, 95%CI [1.15-5.45], p=0.02 in PERL and HR=1.54, 95%CI [1.28-1.84], P=3.8×10-6 in ACCORD). These associations remained significant after adjustment for potential confounders, including baseline GFR and albuminuria. Our findings indicate that CAN is a strong, independent predictor of rapid kidney function decline in both T1D and T2D. Further studies of the link between these two complications may help develop new therapies to prevent kidney function decline in patients with diabetes.

Adapting Betelgeuse’s Dimming Event to A High School Level Astronomy Exercise

This article outlines the process of designing a problem for Astronomy Olympiad at high-school level, based on a recent curious astrophysical event. Betelgeuse, one of the brightest star in the night sky and a supernova candidate, started dimming in October 2019 and reached a record minimum magnitude in February 2020. This extraordinary event piqued curiosity in professional astronomers, amateur astronomers as well as mass media. The problem presented here, tries to build a quantitative model of the event for the students, based on just high school physics. This problem included three models viz., a stellar pulsation model, an exoplanet transit model and a mass loss event model. The students were asked to calculate few physical quantities or parameters to deduce the most suitable model. The entire process of problem design including constraints involved, alternative approaches explored and discarded and the final draft is laid out. It is hoped that this discussion will serve as a guiding light to fellow problem designers and question setters.

Genome-Wide Identification, Expansion, Evolution, and Expression Analysis Reveals ABCB Genes Important for Secondary Cell Wall Development in Moso Bamboo (Phyllostachys edulis)

The ATP-binding cassette subfamily B (ABCB) is an important transporter family, and many members are well known for their auxin transport function. However, reports on the function of the ABCB genes during Moso bamboo development are few. In this study, we identified and characterized 37 PhABCB genes in Moso bamboo and classified them into five subgroups, Ⅰ–Ⅴ. We further observed gene family expansion and gene loss events during the evolution of the PhABCB gene family. It was found that the expansion of the PhABCB family was mainly attributed to the whole-genome duplication and DNA-transposed duplication models. Gene co-expression analysis and quantitative real-time PCR revealed that several PhABCB genes may be involved in the development of the secondary cell wall (SCW) during the rapid growth of Moso bamboo. Through examining their expression in different parts of the bamboo internode where the cell walls exhibited different developmental stages, the roles of eight candidate PhABCBs in the SCW development were further characterized. Of the eight PhABCB genes, PhABCB7, PhABCB11, PhABCB14, and PhABCB21 may be involved in the SCW biogenesis in Moso bamboo. This study provides the basis for discovering the potential role of PhABCB genes in Moso bamboo cell wall development; further studies are needed to elucidate how these PhABCBs function in SCW development by regulating the polar transport of auxin.

A multidrug-resistant Salmonella enterica Typhimurium DT104 complex lineage circulating among humans and cattle in the USA lost the ability to produce pertussis-like toxin ArtAB.

Salmonella enterica subsp. enterica serotype Typhimurium definitive type 104 (DT104) can infect both humans and animals and is often multidrug-resistant (MDR). Previous studies have indicated that, unlike most S. Typhimurium, the overwhelming majority of DT104 strains produce pertussis-like toxin ArtAB via prophage-encoded genes artAB. However, DT104 that lack artAB have been described on occasion. Here, we identify an MDR DT104 complex lineage circulating among humans and cattle in the USA, which lacks artAB (i.e. the ‘U.S. artAB-negative major clade’; n=42 genomes). Unlike most other bovine- and human-associated DT104 complex strains from the USA (n=230 total genomes), which harbour artAB on prophage Gifsy-1 (n=177), members of the U.S. artAB-negative major clade lack Gifsy-1, as well as anti-inflammatory effector gogB. The U.S. artAB-negative major clade encompasses human- and cattle-associated strains isolated from ≥11 USA states over a 20-year period. The clade was predicted to have lost artAB, Gifsy-1 and gogB circa 1985–1987 (95 % highest posterior density interval 1979.0–1992.1). When compared to DT104 genomes from other regions of the world (n=752 total genomes), several additional, sporadic artAB, Gifsy-1 and/or gogB loss events among clades encompassing five or fewer genomes were observed. Using phenotypic assays that simulate conditions encountered during human and/or bovine digestion, members of the U.S. artAB-negative major clade did not differ from closely related Gifsy-1/artAB/gogB-harbouring U.S. DT104 complex strains (ANOVA raw P>0.05); thus, future research is needed to elucidate the roles that artAB, gogB and Gifsy-1 play in DT104 virulence in humans and animals.

Parameter Estimation and Species Tree Rooting Using ALE and GeneRax.

ALE and GeneRax are tools for probabilistic gene tree-species tree reconciliation. Based on a common underlying statistical model of how gene trees evolve along species trees, these methods rely on gene vs. species tree discordance to infer gene duplication, transfer, and loss events, map gene family origins, and root species trees. Published analyses have used these methods to root species trees of Archaea, Bacteria, and several eukaryotic groups, as well as to infer ancestral gene repertoires. However, it was recently suggested that reconciliation-based estimates of duplication and transfer events using the ALE/GeneRax model were unreliable, with potential implications for species tree rooting. Here, we assess these criticisms and find that the methods are accurate when applied to simulated data and in generally good agreement with alternative methodological approaches on empirical data. In particular, ALE recovers variation in gene duplication and transfer frequencies across lineages that is consistent with the known biology of studied clades. In plants and opisthokonts, ALE recovers the consensus species tree root; in Bacteria-where there is less certainty about the root position-ALE agrees with alternative approaches on the most likely root region. Overall, ALE and related approaches are promising tools for studying genome evolution.

Management of patients with chronic mesenteric ischemia across three consecutive eras

BackgroundEndovascular intervention (EI) is the most commonly used modality for chronic mesenteric ischemia (CMI). Since the inception of this technique, numerous publications have reported the associated clinical outcomes. However, no publication has reported the comparative outcomes over a period of time in which both the stent platform and adjunctive medical therapy have evolved. This study aims to assess the impact of the concomitant evolution of both the endovascular approach and optimal guideline-directed medical therapy (GDMT) on CMI outcomes over three consecutive time eras. MethodsA retrospective review at a quaternary center from January 2003 to August 2020 was performed to identify patients who underwent EIs for CMI. The patients were divided into three groups based on the date of intervention: early (2003-2009), mid (2010-2014), and late (2015-2020). At least one angioplasty/stent was performed for the superior mesenteric artery (SMA) and/or celiac artery. The patients' short- and mid-term outcomes were compared between the groups. Univariable and multivariable Cox proportional hazard models were also conducted to evaluate the clinical predictors for primary patency loss in SMA only subgroup. ResultsA total of 278 patients were included (early, 74; mid, 95; late, 109). The overall mean age was 71 years, and 70% were females. High technical success (early, 98.6%; mid, 100%; late, 100%; P = .27) and immediate resolution of symptoms (early, 86.3%; mid, 93.7%; late, 90.8%; P = .27) were noted over the three eras. In both the celiac artery and SMA cohorts, the use of bare metal stents (BMS) declined over time (early, 99.0%; mid, 90.3%; late, 65.5%; P < .001) with a proportionate increase in covered stents (CS) (early, 0.99%; mid, 9.7%; late, 28.9%; P < .001). The use of postoperative antiplatelet and statins has increased over time (early, 89.2%; mid, 97.9%; late, 99.1%; P = .003) and (early, 47%; mid, 68%; late, 81%; P = .001), respectively. In the SMA stent-only cohort, no significant differences were noted in primary patency rates between BMS and CS (hazard ratio, 0.95; 95% confidence interval, 0.26-2.87; P = .94). High-intensity preoperative statins were associated with fewer primary patency loss events compared to none/low- or moderate-intensity statins (hazard ratio, 0.30; 95% confidence interval, 0.11-0.72; P = .014). ConclusionsConsistent outcomes were observed for CMI EIs across three consecutive eras. In the SMA stent-only cohort, no statistically significant difference in early primary patency was noted for CS and BMS, making the use of CS at additional cost controversial and possibly not cost effective. Notably, the preoperative high-intensity statins were associated with improved SMA primary patency. These findings demonstrate the importance of guideline-directed medical therapy as an essential adjunct to EI in the treatment of CMI.

Terrorism Definiens in Terrorism Insurance

The terrorism insurance market is a constantly growing industry as a result of the rise in terrorism and associated violence around the world. This trend has captured the attention of the Indian insurance sector as well. More and more people, companies, and organizations are getting insurance to protect themselves in case a terrorist attack occurs in the future. However, what exactly is terrorism insurance? Is it given under the Unlawful Activities (Prevention) Amendment Act, 2008 or any other related and applicable national or state legislation formulated? Terrorism insurance offers coverage for damages resulting from the aforementioned terrorist acts or guarantees to hold the insurer harmless in the event of such losses. The Indian Market Terrorism Risk Insurance Pool, which is managed by the Insurance Regulatory and Development Authority, is now used by general insurers to offer property insurance. As foreign re-insurers withdrew their terrorist coverage following the 9/11 attacks in the United States of America, general insurers took the initiative to create the pool in April 2002. The cost of terrorism insurance, according to insurers, has decreased recently because there haven’t been any significant losses in the pool. The pool’s capacity has increased to 4,500 crore. But, the recent terrorist attacks in Paris and London as well as the ongoing enemy infiltration over our borders have stoked panic, leading to a rise in terrorism insurance in India. Despite the pool taking advantage of this fear, there is no legal framework in place to control it. While the United States and other nations have laws covering similar matters, this research study examines whether India also needs such legislation

Impact of deoxygenation and warming on global marine species in the 21st century

Abstract. Ocean temperature and dissolved oxygen shape marine habitats in an interplay with species' physiological characteristics. Therefore, the observed and projected warming and deoxygenation of the world's oceans in the 21st century may strongly affect species' habitats. Here, we implement an extended version of the Aerobic Growth Index (AGI), which quantifies whether a viable population of a species can be sustained in a particular location. We assess the impact of projected deoxygenation and warming on the contemporary habitat of 47 representative marine species covering the epipelagic, mesopelagic, and demersal realms. AGI is calculated for these species for the historical period and into the 21st century using bias-corrected environmental data from six comprehensive Earth system models. While habitat viability decreases nearly everywhere with global warming, the impact of this decrease is strongly species dependent. Most species lose less than 5 % of their contemporary habitat volume at 2 ∘C of global warming relative to preindustrial levels, although some individual species are projected to incur losses 2–3 times greater than that. We find that the in-habitat spatiotemporal variability of O2 and temperature (and hence AGI) provides a quantifiable measure of a species' vulnerability to change. In the event of potential large habitat losses (over 5 %), species vulnerability is the most important indicator. Vulnerability is more critical than changes in habitat viability, temperature, or pO2 levels. Loss of contemporary habitat is for most epipelagic species driven by the warming of ocean water and is therefore elevated with increased levels of global warming. In the mesopelagic and demersal realms, habitat loss is also affected by pO2 decrease for some species. Our analysis is constrained by the uncertainties involved in species-specific critical thresholds, which we quantify; by data limitations on 3D species distributions; and by high uncertainty in model O2 projections in equatorial regions. A focus on these topics in future research will strengthen our confidence in assessing climate-change-driven losses of contemporary habitats across the global oceans.

Retained chromosomal integrity following CRISPR-Cas9-based mutational correction in human embryos

Human germline gene correction by targeted nucleases holds great promise for reducing mutation transmission. However, recent studies have reported concerning observations in CRISPR-Cas9-targeted human embryos, including mosaicism and loss of heterozygosity (LOH). The latter has been associated with either gene conversion or (partial) chromosome loss events. In this study, we aimed to correct a heterozygous basepair substitution in PLCZ1, related to infertility. In 36% of the targeted embryos that originated from mutant sperm, only wild-type alleles were observed. By performing genome-wide double-digest restriction site-associated DNA sequencing, integrity of the targeted chromosome (i.e., no deletions larger than 3 Mb or chromosome loss) was confirmed in all seven targetedGENType-analyzed embryos (mutant editing and absence of mutation), while short-range LOH events (shorter than 10 Mb) were clearly observed by single-nucleotide polymorphism assessment in two of these embryos. These results fuel the currently ongoing discussion on double-strand break repair in early human embryos, making a case for the occurrence of gene conversion events or partial template-based homology-directed repair.

Identification of acyl-CoA-binding protein gene in Triticeae species reveals that TaACBP4A-1 and TaACBP4A-2 positively regulate powdery mildew resistance in wheat

Plant acyl-CoA-binding proteins (ACBPs), which contain the conserved ACB domain, participate in multiple biological processes, however, there are few reports on wheat ACBPs. In this study, the ACBP genes from nine different species were identified comprehensively. The expression patterns of TaACBP genes in multiple tissues and under various biotic stresses were determined by qRT-PCR. The function of selected TaACBP genes was studied by virus-induced gene silencing. A total of 67 ACBPs were identified from five monocotyledonous and four dicotyledonous species and divided into four classes. Tandem duplication analysis of the ACBPs suggested that tandem duplication events occurred in Triticum dicoccoides, but there was no tandem duplication event in wheat ACBP genes. Evolutionary analysis suggested that the TdACBPs may have experienced gene introgression during tetraploid evolution, while TaACBP gene loss events occurred during hexaploid wheat evolution. The expression pattern showed that all the TaACBP genes were expressed, and most of them were responsive to induction by Blumeria graminis f. sp. tritici or Fusarium graminearum. Silencing of TaACBP4A-1 and TaACBP4A-2 increased powdery mildew susceptibility in the common wheat BainongAK58. Furthermore, TaACBP4A-1, which belonged to class III, physically interacted with autophagy-related ubiquitin-like protein TaATG8g in yeast cells. This study provided a valuable reference for further investigations into the functional and molecular mechanisms of the ACBP gene family.

Coping Strategies to Improve Financial Well-Being During the COVID-19 Pandemic in an Emerging Economy

This article examines the influence of financial self-efficacy, financial behavior, financial stress, and financial stressor events on the financial well-being (FWB) of Malaysians during the COVID-19 pandemic. The article then analyzes the moderating effects of three types of coping strategies (self-coping, borrowing, and government aid) on the relationship between financial stress and financial stressor events (income loss, creditor, and legal action stressor events) and FWB. Analyses from a sample of 738 Malaysian working adults indicated that financial self-efficacy and financial behavior were positively related to FWB, while financial stress and financial stressor events were negatively related to FWB. Self-coping and borrowing reduced the negative effect of financial stress on FWB, while the government aid coping strategy reduced the impact of income loss and legal action stressor events on FWB. The study contributes to the literature by examining coping strategies and financial stressor events by three distinct categories in the context of an emerging market.

Legal Protection and Liability for Multimodal Transport Operators in The Transport of Dangerous and Toxic Goods

Legal protection protects human rights that harm other people, and every human being is provided with this protection in order they can savor all of their legal right. In other words, legal protection is various legal remedies that must be provided by law enforcement officials to provide a sense of security, both physically and mentally as well as interference from various threats originating from any party. In contrast, transportation law can be interpreted as the overall legal norms and principles governing relationships and consequences of transportation law. This research shows that a form of legal protection for transportation service users can be provided in the form of preventive and repressive legal protection. The responsibility given to service users is in the form of compensation or compensation in the event of damage or loss of goods in the transportation process. There are two approaches used by researchers in this thesis, namely the Legislative Approach and the Conceptual Approach. In this legislative approach, the approach in legal research that provides an analytical point of view of problem-solving legal research is seen from the aspects of the legal concepts that lie behind it or even can be seen from the values contained in the normalization of regulation with the concepts used. Most of these approaches are used to understand the concepts related to normalization in legislation, whether they are in accordance with the spirit contained in the underlying legal concepts.

Problems of recovery of lost profits in the organization of freight rail transportation

The interests of clients of the railway industry and Russian Railways in matters of recovery and compensation for “lost profits” and “lost opportunities” are not considered and regulated in laws and by-laws regarding railway transportation. Claim work is based on compensation for real damage both from users of railway transport services and from the Russian Railways holding.An algorithm for the formation, submission and resolution of claims in the provision of rail transportation services is considered. The functionality of the personal account for the clients of JSC “Russian Railways” of the project “Electronic Claimant” was analyzed. The importance of developing a basic formula that takes into account the factors affecting the amount of lost profits is indicated. The existing scheme for conducting recourse work to recover losses of Russian Railways JSC is given and a scheme for conducting claim work to compensate for lost profits of Russian Railways JSC on the basis of a unified automated system of act and claim work is presented. It is proposed as a basis for further elaboration of this issue, a mechanism for rebilling in the event of final losses from a failed transportation for clients of the Russian Railways holding. The expediency of applying a possible replacement transaction when the company finds another counterparty is also considered. The application of these measures will make it possible to create equal competitive conditions in the market for all customers and the Russian Railways holding.

Genomes of fungi and relatives reveal delayed loss of ancestral gene families and evolution of key fungal traits

Fungi are ecologically important heterotrophs that have radiated into most niches on Earth and fulfil key ecological services. Despite intense interest in their origins, major genomic trends of their evolutionary route from a unicellular opisthokont ancestor to derived multicellular fungi remain poorly known. Here we provide a highly resolved genome-wide catalogue of gene family changes across fungal evolution inferred from the genomes of 123 fungi and relatives. We show that a dominant trend in early fungal evolution has been the gradual shedding of protist genes and the punctuated emergence of innovation by two main gene duplication events. We find that the gene content of non-Dikarya fungi resembles that of unicellular opisthokonts in many respects, owing to the conservation of protist genes in their genomes. The most rapidly duplicating gene groups included extracellular proteins and transcription factors, as well as ones linked to the coordination of nutrient uptake with growth, highlighting the transition to a sessile osmotrophic feeding strategy and subsequent lifestyle evolution as important elements of early fungal history. These results suggest that the genomes of pre-fungal ancestors evolved into the typical filamentous fungal genome by a combination of gradual gene loss, turnover and several large duplication events rather than by abrupt changes. Consequently, the taxonomically defined Fungi represents a genomically non-uniform assemblage of species.

The impact of asymmetry of information and different ambiguity reactions on insurance demand

We extend the model of ex-ante asymmetric information in the insurance market of Stiglitz (1977) by incorporating consumers’ reactions to uncertainty. Specifically, we assume that some agents are able to assign a precise probability measure to the event of loss (Savage, 1954), whilst others are not. The behavior of the latter group complies either with proba-bilistic sophistication or ambiguity aversion as modeled by maxmin expected utility (Gilboa and Schmeidler, 1989). When the former class exhibits sufficient pessimism, these two types are virtually indistinguishable when exposed to rare hazards. Thus, pooling constitutes as an optimal solution to the problem of the monopolist.

A mouse model of repeated traumatic brain injury-induced hearing impairment: Early cochlear neurodegeneration in the absence of hair cell loss

PurposeTraumatic Brain Injury (TBI) is a major cause of death and disability worldwide. Mounting evidence suggests that even mild TBI injuries, which comprise >75% of all TBIs, can cause chronic post-concussive neurological symptoms, especially when experienced repetitively (rTBI). The most common post-concussive symptoms include auditory dysfunction in the form of hearing loss, tinnitus, or impaired auditory processing, which can occur even in the absence of direct damage to the auditory system at the time of injury. The mechanism by which indirect damage causes loss of auditory function is poorly understood, and treatment is currently limited to symptom management rather than preventative care. We reasoned that secondary injury mechanisms, such as inflammation, may lead to damage of the inner ear and parts of the brain used for hearing after rTBI. Herein, we established a model of indirect damage to the auditory system induced by rTBI and characterized the pathology of hearing loss. MethodsWe established a mouse model of rTBI in order to determine a timeline of auditory pathology following multiple mild injuries. Mice were subject to controlled cortical impact at the skull midline once every 48 h, for a total of 5 hits. Auditory function was assessed via the auditory brainstem response (ABR) at various timepoints post injury. Brain and cochleae were collected to establish a timeline of cellular pathology. ResultsWe observed increased ABR thresholds and decreased (ABR) P1 amplitudes in rTBI vs sham animals at 14 days post-impact (dpi). This effect persisted for up to 60 days (dpi). Auditory temporal processing was impaired beginning at 30 dpi. Spiral ganglion degeneration was evident at 14 dpi. No loss of hair cells was detected at this time, suggesting that neuronal loss is one of the earliest notable events in hearing loss caused by this type of rTBI. ConclusionsWe conclude that rTBI results in chronic auditory dysfunction via damage to the spiral ganglion which occurs in the absence of any reduction in hair cell number. This suggests early neuronal damage that may be caused by systemic mechanisms similar to those leading to the spread of neuronal death in the brain following TBI. This TBI-hearing loss model provides an important first step towards identifying therapeutic targets to attenuate damage to the auditory system following head injury.