It is often suggested that during development the brain barriers are immature. This argument stems from teleological interpretations and experimental observations of the high protein concentrations in fetal cerebrospinal fluid (CSF) and decreases in apparent permeability of passive markers during development. We argue that the developmental blood–CSF barrier restricts the passage of lipid‐insoluble molecules by the same mechanism as in the adult (tight junctions) rendering the paracellular pathway an unlikely route of entry. Instead, we suggest that both protein and passive (...) markers are transferred across the epithelium through a transcellular route. We propose that changes in volume of distribution can largely explain the decrease in apparent permeability for passive markers and that developmentally regulated cellular transfer explains changes in CSF protein concentrations. The blood–CSF tight junctions are functionally mature from very early in development, and it appears that transfer from blood into embryonic brain occurs predominately via CSF rather than the vasculature. BioEssays 30:237–248, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Immunological mechanisms and therapy approaches in psychotic syndromes were recently supported by the discovery of autoantibody-associated limbic and non-limbic encephalitis. However, how clinical diagnostic procedures in psychiatry should be adapted to these new insights is still unclear. In this study, we analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and their association with cerebral MRI (cMRI) and electroencephalographic (EEG) findings. From 2006 until 2013, we acquired 180 CSF samples from psychotic patients. Between 2006 and 2009, CSF examinations were only performed (...) in cases in which organic brain disease was suspected. Since then, this procedure has been integrated into our routine diagnostic workup. CSF basic diagnostics were supplemented by measuring antineuronal antibodies against intracellular synaptic antigens, antibodies against intracellular onconeural antigens, antibodies against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs and EEGs were conducted. We found white cell counts elevated in 3.4% of the cases, albumin quotient elevated in 21.8%, and protein concentration elevated in 42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the cases. Antibodies measured against neuronal cell surface antigens were positive in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study was the high prevalence of CSF and autoantibody abnormalities in 54.4% of psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal findings. Our results are discussed with regard to the concept of immunological encephalopathy. Future studies should analyze the efficacy of immunomodulatory therapies. (shrink)

Immunity against SARS‐CoV‐2 that is acquired by convalescent COVID‐19 patients is examined in reference to (A) the Th17 cell generation system in psoriatic epidermis and (B) a recently discovered phenomenon in which Th17 cells are converted into tissue‐resident memory T (TRM) cells with Th1 phenotype. Neutrophils that are attracted to the site of infection secrete IL‐17A, which stimulates lung epithelial cells to express CCL20. Natural Th17 (nTh17) cells are recruited to the infection site by CCL20 and expand in the presence (...) of IL‐23. These nTh17 cells are converted to TRM cells upon encounter with SARS‐CoV‐2 and continue to exist as ex‐Th17 cells, which exert Th1‐like immunity during a memory response. G‐CSF can induce nTh17 cell accumulation at the infection site because it promotes neutrophil egress from the bone marrow. Hence, G‐CSF may be effective against COVID‐19. Administration of G‐CSF to patients infected with SARS‐CoV‐2 is worth a clinical trial. (shrink)

Mouse pre‐implantation development appears to be under the control of paracrine and autocrine growth factors. The epithelium of the oviduct and the uterus together, with the population of macrophages and lymphocytes present in the reproductive tract from the onset of pregnancy, are thought to be the major sources of paracrine growth factors targeted to the developing embryos. Some of the growth factors are synthesized by both uterine epithelial cells and activated lympho‐hematopoietic cells, suggesting a partial overlap of the regulatory signals (...) used by the reproductive and lympho‐hematopoietic systems. Such growth factors may be the long sought‐after mediators of the synchrony between the pre‐implantation embryo and the sex‐steroid hormone‐induced changes in the uterus. (shrink)

A unique feature of the vertebrate brain is the ventricular system, a series of connected cavities which are filled with cerebrospinal fluid (CSF) and surrounded by neuroepithelium. While CSF is critical for both adult brain function and embryonic brain development, neither development nor function of the brain ventricular system is fully understood. In this review, we discuss the mystery of why vertebrate brains have ventricles, and whence they originate. The brain ventricular system develops from the lumen of the neural tube, (...) as the neuroepithelium undergoes morphogenesis. The molecular mechanisms underlying this ontogeny are described. We discuss possible functions of both adult and embryonic brain ventricles, as well as major brain defects that are associated with CSF and brain ventricular abnormalities. We conclude that vertebrates have taken advantage of their neural tube to form the essential brain ventricular system. (shrink)

Recently, there has been much research into conceptual engineering in connection with feminist inquiry and activism, most notably involving gender issues, but also sexism and misogyny. Our paper contributes to this research by explicating, in a principled manner, a series of other concepts important for feminist research and activism, to wit, feminist political identity terms. More specifically, we show how the popular Conceptual Spaces Framework (CSF) can be used to identify and regiment concepts that are central to feminist research, focusing (...) especially on feminism in France. According to the CSF, concepts can be represented geometrically, as regions in similarity spaces. A particular strength of the CSF framework is its empirically-focused methodology, which allows researchers to infer the boundaries of concepts from empirical data, thus eliminating the need to strongly rely on intuitions about meanings. This is shown to be especially valuable for the explication of concepts relating to feminist political identity, given that the intuitions of feminist scholars and activists about what would appear to be core concepts in the area tend to be poorly aligned or even conflicting. We report the results from an empirical categorization study conducted among French feminists and show how they support the view that the CSF can contribute to both the conceptual engineering project and our understanding of the structure of social reality. (shrink)

The catch 22 situation in psychiatry is that for precise diagnostic categories/criteria, we need precise investigative tests, and for precise investigative tests, we need precise diagnostic criteria/categories; and precision in both diagnostics and investigative tests is nonexistent at present. The effort to establish clarity often results in a fresh maze of evidence. In finding the way forward, it is tempting to abandon the scientific method, but that is not possible, since we deal with real human psychopathology, not just concepts to (...) speculate over. Search for clear-cut definitions/diagnostic criteria in psychiatry must be relentless. There is a greater need to be ruthless and blunt in this, rather than being accommodative of diverse opinions. Investigative tests - psychological, serum, CSF, or neuroimaging - are only corroborative at present; they need to become definitive. Medicalisation appears most prominent in psychiatry; so, diagnostic proliferation and fuzziness appear inevitable. And yet, the established diagnostic entities need to forward greater and conclusive precision. Also, the need for clarity and precision must outweigh pandering to and mollifying diverse interests, moreso in the upcoming revision of diagnostic manuals. This is specially because the DSM-5, being an Association manual, may need to accommodate powerful member lobbies; and ICD-11 may similarly need to cater to diverse country lobbies. Finding precise biological correlates of psychiatric phenomena, whether through neuroimaging, molecular neurobiology and/or neurogenomics, is the right way forward. It is in the 1.5-kg structure in the cranium that all secrets of psychiatric conditions lie. Social forces, behavioural modification, psychosocial restructuring, study of intrapsychic processes, and philosophical insights are not to be discounted, but they are supplementary to the primary goal - studying and deciphering those brain processes that result in psychiatric malfunction. Experimental breakthroughs, both in psychiatric aetiology and therapeutics, will come mainly from biology and its adjunct, psychopharmacology; while supplementary and complementary breakthroughs will come from the psychosocial, cognitive and behavioural approaches; the support base will come from phenomenology, epidemiology, nosology and diagnostics; while insights and leads can hopefully come from many fields, especially the psychosocial, the behavioural, the cognitive and the philosophical. Major energies must now be marshalled towards finding biomarkers and deciphering the precise phenotype-genotype-endophenotype axis of psychiatric disorders. Energies also need to be focussed on unravelling those critical processes in the brain that tip the scale towards psychiatric disorders. At how those critical processes are set into motion by forces de novo, in utero, in the genes and their expression, by the environment's psychopathological social forces - stress, peer pressure, poverty, deprivation, alienation, malnutrition, discrimination of various types (caste, gender, race, etc.), mass conflicts (war, terror attacks, etc.), disasters (natural and man-made), religious/ideological fascism - or social institutions like marriage, family, work place, political governance, etc. Ultimately, we must decipher how the brain goes into malfunction when such varied forces impinge on it, which precise cortical areas and neuronal cellular and molecular processes are involved in such malfunction and its manifestation, as also which of these are involved when malfunction ceases and health is restored, and the psychosocial processes and institutions which aid such health restoration, as also those which promote well-being and help in primary prevention. Emphasis on the brain and its intimate neurological and molecular mechanisms will not impinge on, or nullify, importance of the 'mind,' wherein subtle and gross brain functions in the form of behaviour, thought and emotions in all their ramifications will continue to be the focus of psychological, cognitive, sociological, psychopharmacological, behavioural and philosophical research. Progress in brain research must move in tandem with progress in 'mind' research. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Down the Medical Rabbit HoleAnonymous ThreeEditors’ Note: This woman’s child was treated for an astrocytoma at 8–years–old. The surgery included tumor resection and placement of a ventricular peritoneal shunt, which manages the flow, drainage and pressure of cerebral spinal fluid (CSF ) throughout the brain and spinal column.Am I aliveWhat’s this pain I feelAching insideMaking me kneelDown to the groundSubmissiveLike I’ve been sentTo Hell–AnonymousI am making a time capsule (...) of words. If I don’t write these words now, how will I remember? It is for her. She will need these words to know who she is.They took her at the lowest point, when she was barfing and admitting she needed to be in the emergency room (ER). And they stripped her of the ability to use her words to defend herself.“There’s really no reason for you to be here. The x–ray of your shunt tubing looks fine. The CT of your head looks fine. You should think about going home.” I start to speak, but she is speaking so I wait to hear what she will say.“I was worried since my side hurts so bad that maybe it was my appendix and I didn’t want it to burst and then have the infection go up my shunt, I know someone that that happened to, and then my head was exploding and I threw–up.”“That’s when we have to come in to the ER “ I say. “We’ve done this before. We wait until the last possible moment before coming. You’ve seen us here for almost 12 hours now, but we waited more than 24 hours before coming and she was just like this the whole time.”“One of the only things we can see that might be wrong is that we think she might be constipated.”“I try to stay on top of it, ”My 20-year-old says. “I’ve been taking more pain killers lately because my head is always killing me and I push myself to make it to class. But I take stuff to make it easier for me so I don’t get constipated. Last Wednesday during class my head was exploding and I had to vomit. I don’t think my shunt is broken. But...”I interrupt, which is my job, because they are not hearing her, still she gives me hated looks, “She spends two days in bed laying basically flat so she can spend one day or even a few hours vertical the next day. This has been progressing for a while. Last May she had surgery for a CSF leak in her spine. But the headaches are different this time.”“We really think you should consider going home, the tests we’ve done look good.”This is the part that always happens, the part where I say you go into the twilight zone or down Alice’s rabbit hole. In May I had to demand that she have the right to sit up, pain free in the hospital for two hours before leaving. And that is how they admitted her, Mother wants her to sit upright.Here we are again 15 days before Christmas back in the ER—they, meaning the white coats, disbelieving us.She broke then, like a piece of a falling statue, an arm or a leg or part of a shoulder busting off. “I can’t go on like this, my head is exploding and I push myself so hard just to walk across campus [End Page 18] and when I’m sitting in class I know I shouldn’t be there, it’s just so hard. I had a surgery in April last year to replace my shunt and I never really bounced back, and then they found the cyst in my back and the leak and after that surgery I just couldn’t get any energy and my head still hurt.”They don’t know that she never tells anyone any of this.“I know you don’t see anything on her scans,” I say. They always look fine... (shrink)

Once hematopoiesis is established in the bone marrow, a continuous egress of hematopoietic stem cells (HSCs) to the periphery occurs at a low frequency. It has been proposed that this phenomenon is part of a regenerative homeostatic mechanism that ensures the maintenance of hematopoiesis through the life of the individual. The administration of certain cytotoxic drugs or cytokines can enhance the mobilization of hematopoietic progenitors to the periphery. During the past 15 years, granulocyte‐colony stimulating factor (G‐CSF) has been used as (...) a standard cytokine for mobilization protocols in experimental models and in humans. Despite extensive efforts by multiple groups, a definitive mechanism explaining its role in mobilization has not been provided. In a recent paper, Katayama et al.,1 through a series of clever associations supported by well‐defined experimental systems, proposed that signals through the sympathetic nervous system modify the activity of the hematopoietic niche, acting as regulators of the mobilization of hematopoietic progenitors. This surprising finding adds a new level of complexity to the cellular milieu responsible for generation and maintenance of the hematopoietic niche. BioEssays 28: 687–691, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Previous studies have demonstrated that orientation-specific deprivation in early life can lead to neural deficits of spatial vision in certain space, and can even result in meridional amblyopia. Individuals with astigmatism are the optimal and natural models for exploring this asymmetric development of spatial vision in the human visual system. This study aims to assess the contrast sensitivity function and EEG signals along two principal meridians in participants with regular astigmatism when being optimal optical corrected. Twelve participants with astigmatism and (...) thirteen participants with were recruited in the current study. CSFs and spatial sweep visual evoked potentials were measured with vertical and horizontal sinewave gratings along two principal meridians monocularly. Area under log CSF, spatial frequency threshold corresponding to 80% contrast gratings, and CSF acuity were calculated from CSF test. In addition, sVEP amplitudes and thresholds were calculated with the recursive least square method. Participants with astigmatism exhibited marked vertical-horizontal resolution disparities even after they were corrected with optimal optical corrections. CSF tests showed that AULCSF along weak meridian was lower than that along strong meridian in both groups. Significant meridional disparity of CSF acuity was also found in both groups. In addition, the MA group showed larger meridional disparity compared to the AST group. Spatial sVEP thresholds also supported the existence of marked meridional disparity. Our results suggest that meridian-specific partial deprivation in early life might lead to monocularly asymmetric development of spatial vision in the human visual system. In terms of application, we tested the feasibility and reliability of adopting psychophysical and EEG scalings to investigate the asymmetric development of spatial vision related to astigmatism. These paradigms are potentially applicable to reduce and even eliminate the meridional disparity in the primary visual cortex by adopting perceptual learning or other vision-related interventions. (shrink)

Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event. Frailty is most frequently assessed in the old using the Clinical Frailty Scale (CSF) which ranks frailty from 1 to 9. This assessment typically takes less than one minute and is not validated in patients with learning difficulties or those under 65 years old. The National Institute for Health and Care Excellence (NICE) developed guidelines that use “frailty” as one of the priority-setting criteria for (...) how scarce, but potentially lifesaving, health care resources should be allocated during the COVID-19 pandemic. Similar guidelines have been developed elsewhere. This paper discusses the ethical implications of such rationing and argues that this is an unproven and ethically problematic form of health care rationing. It specifically discusses: (1) how the frailty ascription becomes a self-fulfilling prophecy, (2) the problematic use of “frailty” in COVID-19 “triage,” (3) the circularity of the link between age and frailty, (4) indirect discrimination because of the use of a seemingly neutral criterion in health care rationing, and (5) the difficult link between comorbidities and frailty. It is found that there was no research into the use of global frailty scores as a criterion for access to acute treatment before January 2020 and so it is concerning how readily frailty scoring has been adopted to ration access to potentially lifesaving treatments. Existing gerontological frailty scoring systems have not been developed for this purpose, and repurposing them creates significant ethical issues. (shrink)

This article is intended to serve as a reminder of the themes that have been present in Christian spiritual formation through the centuries. In a WISDOM orientation we ground our approach to CSF in Scripture, in theology, and in “best practices,” yet we also seek to thoughtfully locate CSF within specific contexts. The WISDOM acronym reminds us that formation must involve: Wise planning, where the leaders prayerfully seek to implement what is needed in a specific situation; Intentionality, calling people to (...) commit to walk differently from the ways of the world; Scripture, salvation, and Spirit, where the Salvation message and the Spirit-led mission of the whole of Scripture provides the framework for CSF; Discipleship, where the end of CSF is the imitation of Jesus Christ; Optimism, where we pursue our formation in an atmosphere of hope and expectation of change; and Means. (shrink)

In general, only one diffusion model would be applied to whole field-of-view voxels in the intravoxel incoherent motion-magnetic resonance imaging study. However, the choice of the applied diffusion model can significantly influence the estimated diffusion parameters. The quality of the diffusion analysis can influence the reliability of the perfusion analysis. This study proposed an optimal model mapping method to improve the reliability of the perfusion parameter estimation in the IVIM study. Six healthy volunteers. Volunteers were examined using a 3.0 Tesla (...) scanner. IVIM-MRI of the brain was applied at 17 b-values ranging from 0 to 2,500 s/mm2. The Gaussian model, the Kurtosis model, and the Gamma model were found to be optimal for the CSF, white matter, and gray matter, respectively. In the mean perfusion fraction analysis, the GM/WM ratios were 1.16, 1.80, 1.94, and 1.54 ; in the mean pseudo diffusion coefficient analysis, the GM/WM ratios were 1.18, 1.19, 1.56, and 1.24. With the optimal model mapping method, the estimated fp and D* were reliable compared with the conventional methods. In addition, the optimal model maps, the associated products of this method, may provide additional information for clinical diagnosis. (shrink)

In the last few years, the molecular and genetic nature of the granulocyte colonystimulating factor, which controls proliferation and differentiation of neutrophils, has been characterized. Recent clinical application of G‐CSF proves that this hormone is effective in the treatment of patients suffering from neutropenia.

The cyclic opeptide Cyclosporinee A (CsA) is best known as the immunosuppressive drug which has revoulutionized organ transplantation. It selectively suppresses T cell activation by blocking the transcription of cytokine genes such as IL‐2 at the level of transxcription factor modulation. The structurally unrelated immuniusuppressant FK 506 acts on the same pathway and blocks cytokine gene expression. In contrast, rapamycin, a structural analoguwe of FK 506, interferes with the immune response at a different level, by blocking the response induced by (...) ctytokines such as IL‐2.Although these drugs have been most studied for their immunosuppressive activities, it is clear that their effects on cytokine pathways extend far beyond the scole IL‐2.‐mediated responses involved in the immune response. IFor instance, CsA and FK 506 inhibit the transcription of IL‐3, IL‐4, IFNγ, TNFα or GM‐CSF by activated T cells, and rapamycin has been shown to blcock the response to various growth factors such as IL‐3, IL‐4 or IL‐6.Here, we receap what is known about the effects of CsA, FK 506 and rapamycin on hematopoiesis in vitro and in vivo and extrapolate on what these drugs can teach us aboput the physiological role of cytokines for hematopoiesis. (shrink)

Mammalian oocytes exhibit a series of cell cycle transitions that coordinate the penultimate events of meiosis with the onset of embryogenesis at fertilization. The execution of these cell cycle transitions, at G2/M of meiosis‐I and metaphase/anaphase of meiosis I and II, involve both biosynthetic and post‐translational modifications that directly modulate centrosome and microtubule behavior. Specifically, somatic cells alter the signal transduction pathways in the oocyte and influence the expression of maturation promoting factor (MPF) and cytostatic factor (CSF) activity through a (...) microtubule‐dependent mechanism. The regulation of the oocytes' cell cycle machinery by hormone‐mediated somatic cell signals, involving both positive and negative stimuli, ensures that meiotic cell cycle progression is synchronized with the earliest pivotal events of mammalian reproduction. (shrink)

Early life stress precedes alterations to neuro-immune activation, which may mediate an increased risk for stress-related psychiatric disorders, potentially through alterations of central kynurenine pathway metabolites, the latter being relatively unexplored. We hypothesized that ELS in a non-human primate model would lead to a reduction of neuroprotective and increases of neurotoxic KP metabolites. Twelve adult female bonnet macaques reared under conditions of maternal variable foraging demand were compared to 27 age- and weight-matched non-VFD-exposed female controls. Baseline behavioral observations of social (...) affiliation were taken over a 12-week period followed by the first cerebrospinal fluid sample. Subjects were then either exposed to a 12-week repeated separation paradigm or assigned to a “no-RSP” condition followed by a second CSF. We used high-performance liquid chromatography for kynurenine, tryptophan, 5-hydroxyindoleacetic acid, kynurenic acid, and anthranilic acid as a proxy for quinolinic acid determination. At baseline, social affiliation scores were reduced in VFD-reared versus control subjects. CSF log KYNA and log KYNA/KYN ratio were lower in VFD-reared versus control subjects. CSF log KYNA/KYN was positively correlated with CSF log ANTH in VFD only. Controlling for log KYNA/KYN, log ANTH was elevated in VFD-reared subjects versus controls. CSF log KYNA/KYN obtained post-RSP was positively correlated with mean social affiliation scores during RSP, specifically in VFD. ELS is associated with a reduced neuroprotective and increased neurotoxic pathway products. That the two contrasting processes are paradoxically correlated following ELS suggests a cross-talk between two opposing KP enzymatic systems. (shrink)

The choroid plexuses (CPs) are involved in the most-basic aspects of neural function including maintaining the extracellular milieu of the brain by actively modulating chemical exchange between the CSF and brain parenchyma, surveying the chemical and immunological status of the brain, detoxifying the brain, secreting a nutritive “cocktail” of polypeptides and participating in repair processes following trauma. This diversity of functions may mean that even modest changes in the CP can have far-reaching effects. Indeed, changes in the anatomy and physiology (...) of the CP have been linked to aging and several CNS diseases. It is also possible that replacing diseased or transplanting healthy CP might be useful for treating acute and chronic brain diseases. This review focuses on the wide-ranging and under-appreciated functions of the CP, alterations of these functions in aging and neurodegeneration, and recent demonstrations of the therapeutic potential of transplanted CP for neural trauma. BioEssays 27:262–274, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The brain ventricular system is a series of connected cavities, filled with cerebrospinal fluid (CSF), that forms within the vertebrate central nervous system (CNS). The hollow neural tube is a hallmark of the chordate CNS, and a closed neural tube is essential for normal development. Development and function of the ventricular system is examined, emphasizing three interdigitating components that form a functional system: ventricle walls, CSF fluid properties, and activity of CSF constituent factors. The cellular lining of the ventricle both (...) can produce and is responsive to CSF. Fluid properties and conserved CSF components contribute to normal CNS development. Anomalies of the CSF/ventricular system serve as diagnostics and may cause CNS disorders, further highlighting their importance. This review focuses on the evolution and development of the brain ventricular system, associated function, and connected pathologies. It is geared as an introduction for scholars with little background in the field. (shrink)

Interleukin 5 (IL‐5) is a kind of peptide hormone released from T lymphocytes of mammals infected with microorganisms or parasites. It is an acidic glycoprotein with a molecular mass of 40 to 50 kDa that consists of a homodimer of polypeptides. It controls hematopoiesis so that it increases natural immunity. In the mouse, IL‐5 acts on committed B cells to induce differentiation into Ig‐producing cells and on common progenitors for CD5+ pre‐B cells and CD5+ macrophages to support their survival. The (...) antibodies secreted by CD5+ B cells seem to be responsible for the primary protection against the infection with microorganisms or parasites. It also supports the growth and/or differentiation of eosinophil precursor and mature eosinophils, which can be effective for the removal of parasites in combination with the antibodies against them. Murine IL‐5 receptor (IL‐5R) consists of two different polypeptide chains; αL chain and β chain. The IL‐5R α chain is 60 kDa protein that binds IL‐5 with low affinity. The IL‐5R β chain is a 130 kDa protein which does not bind IL‐5 by itself but is necessary to form the high affinity IL‐5R. The β chain was identified by using one of the anti‐IL‐5R mAb and anti‐IL‐3R mAb as the IL‐3R homologue. This β chain is also used as the β chain of GM‐CSF receptor. This fact suggests that there is a common signaling mechanism among these cytokines and efficient cooperation among them. At the same time, these findings may explain the overlapping role of these cytokines in the development of granulocytes. (shrink)

A comprehensive understanding of the cerebrospinal fluid system is essential for our understanding of health and disease within the central nervous system. The system of CSF refers to all components involved in CSF production, movement, and absorption. In recent years, extensive research has resulted in vastly improved understanding of the CSF system in health and disease. Yet, several aspects remain to be fully clarified, notably along the spinal cord as the preponderance of research has focused on the brain. This review (...) briefly summarizes the CSF system and its implications for CNS diseases and highlights the knowledge gaps that require further research. (shrink)

A variety of studies show that parental absence early in life leads to deleterious effects on the developing CNS. This is thought to be largely because evolutionary-dependent stimuli are necessary for the appropriate postnatal development of the young brain, an effect sometimes termed the “experience-expectant brain,” with parents providing the necessary input for normative synaptic connections to develop and appropriate neuronal survival to occur. Principal among CNS systems affected by parental input are the monoamine systems. In the present study,N= 434 (...) rhesus monkeys (233 males, 201 females) were reared in one of two conditions: as mother-reared controls (MR;n= 269) or without adults with 24-h access to same-aged peers (PR;n= 165). When subjects were six-months-old, they underwent a separation paradigm involving 4, sequential, four-day social separations from their mothers or peers, with each separation followed by three-day reunions with their mothers or their peers. Prior to the separation paradigm, baseline cisternal CSF samples were obtained, as well as at the end of each the four social separations, and after final separation, during a recovery period. CSF was assayed for concentrations of monoamine metabolites and a blood sample was genotyped for the serotonin transporter (5-HTT) genotype. Replicating earlier landmark findings, PR subjects with thesallele exhibited lower baseline concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), when compared to PR subjects homozygous for theLallele. MR subjects were undifferentiated by genotype. PR subjects exhibited lower CSF 5-HIAA concentrations during baseline, but higher CSF 5-HIAA during social separations, when compared to MR subjects. There were rearing effects for the dopamine metabolite homovanillic acid (HVA) and for the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), with PR subjects showing higher HVA and lower MHPG when compared to MR subjects. These findings indicate that there are long-term deficits in the response of monoamines following early maternal absence. The results of this study confirm and extend earlier findings that early parental absence has deleterious consequences for the development of the monoamine systems, and that these consequences are modulated by the 5-HTT genotype. (shrink)

Purpose – The purpose of this paper is to assess the impact of smallholder supply chains on sustainable sourcing to answer the question how food and agribusiness multinationals can best include smallholders in their sourcing strategies and take social responsibility for large-scale sustainable and more equitable supply. A sustainable smallholder sourcing model with a list of critical success factors (CSFs) has been applied on two best-practise cases. In this model, business and corporate social responsibility perspectives are integrated. Design/methodology/approach – The (...) primary data of the value chain analyses of the two smallholder supply chains of a food and agribusiness multinational have been applied. Both cases were of a join research program commissioned by the multinational and a non-governmental organization using the same methods and research tools. Similarities, differences and interference between the cases have been determined and assessed in order to confirm, fine tune or adjust the CSFs. Findings – Both cases could be conceptualized through the smallholder sourcing model. Most CSFs could be found in both cases, but differences were also found, which led to fine tuning of some CSFs: building of a partnership and effective producers organization, providing farm financing and the use of cross-functional teams in smallholder supplier development programs. It was also concluded that the smallholder sourcing model is applicable in different geographical areas. Research limitations/implications – The findings of this study are based on just two cases. More best-practise cases are recommended in order to confirm or to adjust the developed sourcing model and the CSFs. Originality/value – This paper/research fills the need in sustainable supply chain management literature to study supply chains that comply with the triple bottom line concept, rather than supply chains that are just more “green.” Keywords Small- to medium-sized enterprises, Food products, Supply chain management, Developing countries, Business development, Food industry, Commodity markets Paper type Research pape. (shrink)

In this paper, we present a contest success function, which is homogeneous of degree zero and in which the probability of winning the prize depends on the relative difference of efforts. In a simultaneous game with two players, we present a necessary and sufficient condition for the existence of a pure strategy Nash equilibrium. This equilibrium is unique and interior. This condition does not depend on the size of the valuations as in an absolute difference CSF. We prove that several (...) properties of Nash equilibrium with the Tullock CSF still hold in our framework. Finally, we consider the case of n\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$n$$\end{document} players, generalize the previous condition and show that this condition is sufficient for the existence of a unique interior Nash equilibrium in pure strategies. For some parameter values of our CSF and when all players are identical, equilibrium entails full rent dissipation for any number of players. (shrink)

BackgroundConventionally, transcranial direct current stimulation (tDCS) aims to focalize the current reaching the target region-of-interest (ROI). The focality can be quantified by the dose-target-determination-index (DTDI). Despite having a uniform tDCS setup, some individuals receive focal stimulation (high DTDI) while others show reduced focality (“non-focal”). The volume of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) underlying each ROI govern the tDCS current distribution inside the brain, thereby regulating focality.AimTo determine the regional volume parameters that differentiate the focal and (...) non-focal groups.MethodsT1-weighted images of the brain from 300 age-sex matched adults were divided into three equal groups- (a) Young (20 ≤ × < 40 years), (b) Middle (40 ≤ × < 60 years), and (c) Older (60 ≤ × < 80 years). For each group, inter and intra-hemispheric montages with electrodes at (1) F3 and right supraorbital region (F3-RSO), and (2) CP5 and Cz (CP5-Cz) were simulated, targeting the left- Dorsolateral Prefrontal Cortex (DLPFC) and -Inferior Parietal Lobule (IPL), respectively. Both montages were simulated for two current doses (1 and 2 mA). For each individual head simulated for a tDCS configuration (montage and dose), the current density at each region-of-interest (ROI) and their DTDI were calculated. The individuals were categorized into two groups- (1) Focal (DTDI ≥ 0.75), and (2) Non-focal (DTDI < 0.75). The regional volume of CSF, GM, and WM of all the ROIs was determined. For each tDCS configuration and ROI, three 3-way analysis of variance was performed considering- (i) GM, (ii) WM, and (iii) CSF as the dependent variable (DV). The age group, sex, and focality group were the between-subject factors. For a given ROI, if any of the 3 DV’s showed a significant main effect or interaction involving the focality group, then that ROI was classified as a “focal ROI.”ResultsRegional CSF was the principal determinant of focality. For interhemispheric F3-RSO montage, interaction effect (p < 0.05) of age and focality was observed at Left Caudate Nucleus, with the focal group exhibiting higher CSF volume. The CSF volume of focal ROI correlated positively (r ∼ 0.16, p < 0.05) with the current density at the target ROI (DLPFC). For intrahemispheric CP5-Cz montage, a significant (p < 0.05) main effect was observed at the left pre- and post-central gyrus, with the focal group showing lower CSF volume. The CSF volume correlated negatively (r ∼ –0.16, p < 0.05) with current density at left IPL. The results were consistent for both current doses.ConclusionThe CSF channels the flow of tDCS current between electrodes with focal ROIs acting like reservoirs of current. The position of focal ROI in the channel determines the stimulation intensity at the target ROI. For focal stimulation in interhemispheric F3-RSO, the proximity of focal ROI reserves the current density at the target ROI (DLPFC). In contrast, for intrahemispheric montage (CP5-Cz), the far-end location of focal ROI reduces the current density at the target (IPL). (shrink)