Possible role of the cavernous sinus veins in cerebrospinal fluid absorption

The purpose of this investigation was to enhance our understanding of cerebrospinal fluid (CSF) absorption pathways. To achieve this, Microfil (a coloured silastic material) was infused into the subarachnoid space (cisterna magna) of sheep post mortem, and the relevant tissues examined macroscopically and microscopically. The Microfil was taken up by an extensive network of extracranial lymphatic vessels in the olfactory turbinates. In addition however, Microfil also passed consistently through the dura at the base of the brain. Microfil was noted in the spaces surrounding the venous network that comprises the cavernous sinus, in the adventitia of the internal carotid arteries and adjacent to the pituitary gland. Additionally, Microfil was observed within the endoneurial spaces of the trigeminal nerve and in lymphatic vessels emerging from the epineurium of the nerve. These results suggest several unconventional pathways by which CSF may be removed from the subarachnoid space. The movement of CSF to locations external to the cranium via these routes may lead to its absorption into veins and lymphatics outside of the skull. The physiological importance of these pathways requires further investigation

An Application of Rule-based Forecasting to a Situation Lacking Domain Knowledge

Rule-based forecasting (RBF) uses rules to combine forecasts from simple extrapolation methods. Weights for combining the rules use statistical and domain-based features of time series. RBF was originally developed, tested, and validated only on annual data. For the M3-Competition, three major modifications were made to RBF. First, due to the absence of much in the way of domain knowledge, we prepared the forecasts under the assumption that no domain knowledge was available. This removes what we believe is one of RBF\u27s primary advantages. We had to re-calibrate some of the rules relating to causal forces to allow for this lack of domain knowledge. Second, automatic identification procedures were used for six time-series features that had previously been identified using judgment. This was done to reduce cost and improve reliability. Third, we simplified the rule-base by removing one method from the four that were used in the original implementation. Although this resulted in some loss in accuracy, it reduced the number of rules in the rule-base from 99 to 64. This version of RBF still benefits from the use of prior findings on extrapolation, so we expected that it would be substantially more accurate than the random walk and somewhat more accurate than equal weights combining. Because most of the previous work on RBF was done using annual data, we especially expected it to perform well with annual data

Automatic Identification of Time-Series Features for Rule-based Forecasting

Rule-based forecasting (RBF) is an expert system that uses features of time series to select and weight extrapolation techniques. Thus, it is dependent upon the identification of features of the time series. Judgmental coding of these features is expensive and the reliability of the ratings is modest. We developed and automated heuristics to detect six features that had previously been judgmentally identified in RBF: outliers, level shifts, change in basic trend, unstable recent trend, unusual last observation, and functional form. These heuristics rely on simple statistics such as first differences and regression estimates. In general, there was agreement between automated and judgmental codings for all features other than functional form. Heuristic coding was more sensitive than judgment and consequently, identified more series with a certain feature than judgmental coding. We compared forecast accuracy using automated codings with that using judgmental codings across 122 series. Forecasts were produced for six horizons, resulting in a total of 732 forecasts. Accuracy for 30% of the 122 annual time series was similar to that reported for RBF. For the remaining series, there were as many that did better with automated feature detection as there were that did worse. In other words, the use of automated feature detection heuristics reduced the costs of using RBF without negatively affecting forecast accuracy

Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species

BACKGROUND: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. METHODS: Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans), yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. RESULTS: In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. CONCLUSIONS: The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example) may relate either directly or indirectly to a lymphatic CSF absorption deficit

Characterisation and mapping of a <i>Globodera pallida</i> resistance derived from the wild potato species <i>Solanum spegazzinii</i>

The potato cyst nematodes (PCN) Globodera pallida and Globodera rostochiensis are economically important potato pests in almost all regions where potato is grown. One important management strategy involves deployment through introgression breeding into modern cultivars of new sources of naturally occurring resistance from wild potato species. We describe a new source of resistance to G. pallida from wild potato germplasm. The diploid species Solanum spegazzinii Bitter accession CPC 7195 shows resistance to G. pallida pathotypes Pa1 and Pa2/3. A cross and first backcross of S. spegazzinii with Solanum tuberosum Group Phureja cultivar Mayan Gold were performed, and the level of resistance to G. pallida Pa2/3 was determined in progeny clones. Bulk-segregant analysis (BSA) using generic mapping enrichment sequencing (GenSeq) and genotyping-by-sequencing were performed to identify single-nucleotide polymorphisms (SNPs) that are genetically linked to the resistance, using S. tuberosum Group Phureja clone DM1-3 516 R44 as a reference genome. These SNPs were converted into allele-specific PCR assays, and the resistance was mapped to an interval of roughly 118 kb on chromosome VI. This newly identified resistance, which we call Gpa VIlspg, can be used in future efforts to produce modern cultivars with enhanced and broad-spectrum resistances to the major pests and pathogens of potato

Characterisation and mapping of a <i>Globodera pallida</i> resistance derived from the wild potato species <i>Solanum spegazzinii</i>

The potato cyst nematodes (PCN) Globodera pallida and Globodera rostochiensis are economically important potato pests in almost all regions where potato is grown. One important management strategy involves deployment through introgression breeding into modern cultivars of new sources of naturally occurring resistance from wild potato species. We describe a new source of resistance to G. pallida from wild potato germplasm. The diploid species Solanum spegazzinii Bitter accession CPC 7195 shows resistance to G. pallida pathotypes Pa1 and Pa2/3. A cross and first backcross of S. spegazzinii with Solanum tuberosum Group Phureja cultivar Mayan Gold were performed, and the level of resistance to G. pallida Pa2/3 was determined in progeny clones. Bulk-segregant analysis (BSA) using generic mapping enrichment sequencing (GenSeq) and genotyping-by-sequencing were performed to identify single-nucleotide polymorphisms (SNPs) that are genetically linked to the resistance, using S. tuberosum Group Phureja clone DM1-3 516 R44 as a reference genome. These SNPs were converted into allele-specific PCR assays, and the resistance was mapped to an interval of roughly 118 kb on chromosome VI. This newly identified resistance, which we call Gpa VIlspg, can be used in future efforts to produce modern cultivars with enhanced and broad-spectrum resistances to the major pests and pathogens of potato