Early Form Research Articles

Lapscheure, etymologisch verscheurd. Een overzicht van de opvattingen, nieuwe gegevens en een voorstel tot verzoenende oplossing

The etymology of the West Flemish place name Lapscheure remains uncertain and contentious. The dispute involves both elements of the name. Gysseling (1960) interprets the second part, -scheure, as the local phonetic form of 'schuur' (barn), while Mansion (1935) and Tavernier-Vereecken (1954, 1968) suggest it means 'schoor/schor/schorre' (shore/marsh). The oldest records, such as "lappescura" (1019-30), use <u>, with later records showing <eu/ue>, indicating a Middle West Flemish pronunciation of [ø]. Tavernier-Vereecken's attempt to categorize 'schoor/schorre' within a group of ingvaeonisms (like veugel, weunen, bleuzen) lacks support in contemporary West Flemish. Conversely, unambiguous 'schuur' place names, such as the French-Flemish Ruischeure (Fr. Renescure) and Buisscheure (Fr. Buysscheure), suggest a more straightforward interpretation of 'schuur'. Mansion and Tavernier-Vereecken propose that Lapscheure derives from a personal name, such as Lappa or Lappo. Initially, Gysseling, however, considered the name could mean a repaired barn, later suggesting an Indo-European root *lap (‘bright, beautiful’), which gained little traction. The notion of a repaired barn appeared earlier in Tanghe's 1857 "Beschryving van Lapscheure". The noun lap (‘patch’) dates back to the 10th-century Old Dutch Wachtendonk Psalms and exists in all Germanic languages except Gothic. The verb lappen (‘to mend’) first appeared in 1285 (Dordrecht), possibly originating as a Northwest Germanic/Ingvaeonic term. However, naming a prominent barn this way is doubtful, whereas a personal name remains more plausible. The earliest form, with the expressive geminate -pp-, suggests Lappo as a diminutive of the frequent medieval name Landberht/Landbrecht, evolving through forms like Landbo, Lambo, Lampo, and Lampe to Lappe. This analysis aligns with similar transformations seen in medieval names, as discussed by Debrabandere (1980).

The Literary Structure and Schematic Clauses in 1 En. 72:8–32

Abstract This paper presents an analysis of the literary structure of 1 En. 72:8–32, which contains numerical data regarding the changing duration of day and night within the structure of the 364-day year. The central literary section of each month provides the reader with information about the changing length of day and night. The schematic clauses have been analyzed in the context of two Babylonian texts: Tablet BM 17175 + 17284 and Tablet XIV of the Enūma Anu Enlil astrological series. The redactional insertion in v. 27 has been compared with MUL.APIN II i 17, which contains the same information about the sun, but couched in a different terminology. The analysis demonstrates the process of appropriation, reinterpretation, and modification of schematic astronomical knowledge of Babylonian origin, as evidenced by the established relationship between the early form of Babylonian schematic astronomy and chapter 72 of 1 Enoch.

An Excellent Scribe and Servant of the Great Goddess

Summary CT 533, one of the divine scribe spells among the Coffin Texts, is an important early example of the interaction of Thoth and Hathor. The spell’s text, textual history, and theology are extensively discussed in order to expose the early form of the Myth of Distant Goddess as well as early concepts of Thoth’s role in her pacification. The spell’s earliest versions primarily dealt with Thoth as advocate for the deceased, in its later manifestations the spell uses Hathoric material related to the Myth of the Distant Goddess to reinforce these themes. This development is connected to the cult-center at Cusae.

A Rare Case of Early Infantile Neuronal Ceroid Lipofuscinosis: Clinical and Diagnostic Insights

The Aim of the Study: The aim of this work is to show the different specific clinical and paraclinical aspects of ceroid lipofuscinosis in its early infantile form named Santavuori-Haltia disease through a new case.Given its rarety especially in consanguineous populations for better understanding the clinical presentation,progression and management of the disease. Introduction: The neuronal ceroid lipofuscinoses are a group of genetic brain diseases with an autosomal recessive manner characterized by the accumulation of an autofluorescent material in multiple tissues of patients. Clinically, they are progressive decline of mental and motor capacities, epilepsy and visual loss through retinal degeneration . In this work we report the early infantile neuronal ceroid lipofuscinosis or Santavuori-Haltia disease. Report Case: This is a 12-month-old infant from consanguineous parents who has presented with flexion spasms with eyelid clonia since the age of 1 month. The examination found microcephaly, and the neurological examination showed horizontal nystagmus with the absence of ocular pursuit and the presence of a pyramidal and extrapyramidal syndrome. Brain MRI shows delayed myelination. Skin biopsy confirms diagnosis. The Arg122Trp genetic mutation found is the most common one in this disease. Conclusion: Santaviori-Haltia disease is a rare and serious disease, the prognosis is severe, it must be mentioned in the face of psychomotor regression and a picture of encephalopathy. Confirmation of the diagnosis is based on histological and molecular biology data.

Diffusion of the Interrogative Pronoun Sha '啥' From Mandarin to Wu: A View of Dialect Contact / 从方言接触看疑问代词“啥”从官话到吴语的扩散

This article focuses on the source of the interrogative pronoun sha ‘啥’ in Wu dialects, which is a case study of Wu dialects’ historical syntax. It is generally believed that sha ‘啥’ of Wu dialects comes from the fusing of shenme ‘什么’, but this solution has the following problems: Wu dialects have voiced initials, so sha ‘啥’ which is voiceless initial cann’t come from shenme ‘什么’. The article first discusses the geographical distribution and function differences of sha ‘啥’ in Wu dialect, and then reconstructs its early phonetic form. We hypothesize that the fusing of shenme ‘什么’ were considered in the Bianluo area of the Song Dynasty, and then sha ‘啥’ was brought into Wu dialects via the Song southern migration.

Paspalum lepton - a valuable adjunct to the suite of grasses used in grazing systems in the subtropics or a potential weed

Native and exotic C4 grasses currently used in grazing systems in the subtropics have specific limitations with management, decline in feed quality as they mature and variable adaptation to soils and climates, providing opportunities to identify alternative species to complement or replace them. One option is Paspalum lepton (syn. P. nicorae), a sward- forming, rhizomatous grass native to subtropical South America with recognized forage value. An early maturing form of this species has become naturalized in Northern New South Wales since its introduction in the 1940s. More recent introductions with forage and amenity potential are being established vegetatively and by seed as it becomes available. This paper reviews published work on P. lepton and reports largely unpublished results and observations on its performance in research and development studies in subtropical Eastern Australia. The potential value of and threats posed by P. lepton in relation to its adaptation, productivity, competitiveness and role in limiting ingress of existing weedy species are discussed. APG 54281 and APG 54325 are palatable, productive and persistent lines of this grass that have proven to be adapted to livestock production systems in most of the humid lowland subtropics, and to a specific niche in the subtropical uplands of Southeast Queensland where there is a lack of adapted C4 grasses and C3 grasses are only marginally adapted.

Effectiveness of lipid-based nutrient supplementation during the first 1000 days of life for early childhood development: A community-based trial from Pakistan.

A community-based, cluster non-randomized controlled trial was conducted in Kurram district, Pakistan between January 2018 to December 2020. Age-appropriate lipid-based nutrient supplements and health education (sessions conducted in the households) were given to pregnant women and their born children (6-23 months) in the intervention arm (n = 40 clusters) versus health education only in the control arm (n = 40 clusters) to evaluate its effect on child development. The first and second developmental assessments were completed at ~24 months (n = 689) and ~32 months (n = 608), respectively, using the Caregiver-Reported Early Development Instrument Long form. The overall and domain-specific (motor, language, cognitive and socio-emotional) scores were computed with higher scores indicating better child development. Higher development scores, including overall (β = 0.40, 95% confidence interval [CI]: 0.14, 0.65; p = 0.002), cognitive (β = 0.27, 95% CI: 0.10, 0.45; p = 0.002), motor (β = 0.39, 95% CI: 0.22, 0.56; p < 0.001) and language (β = 0.33, 95% CI: 0.14, 0.51; p = 0.001) were reported for children who received the intervention compared to the control arm at first developmental assessment. However, the effect was not sustained after the discontinuation of the intervention. The LNS received by the mothers (during pregnancy and first 6 months after delivery) and by children during 6-23 months of age was beneficial for the children. The trial is registered in the International Standard Randomised Controlled Trial Number Registry (ID: ISRCTN94319790) on December 11, 2017.

A parenting program delivered through existing community-based peer groups to improve early child development in Homabay and Busia Counties, Kenya: study protocol for a cluster-randomized controlled trial

BackgroundPoor early childhood development (ECD) is a major global health concern that is associated with various adverse outcomes over the lifecourse. Parenting interventions especially during the earliest years of life can benefit ECD. However, there is limited evidence from Kenya about the effectiveness of parenting interventions for improving ECD outcomes especially across rural disadvantaged communities. This paper describes the study protocol for an impact and implementation evaluation of a community-based group parenting program that aims to improve ECD in rural Kenya.MethodsWe will conduct a cluster-randomized controlled trial to determine the effectiveness of a parenting program for caregivers of young children in Homabay and Busia counties in Western Kenya. Sixty-four village clusters will be randomly assigned to either the parenting intervention arm or the waitlist control arm with stratification by county. In each village, 10 primary caregivers with a child aged 0–24 months will be enrolled. The parenting program will be delivered through existing peer groups within communities whereby caregivers will receive counseling and psychosocial support to enhance their parenting skills and wellbeing to in turn promote ECD. The intervention curriculum comprises 21 sessions targeting various nurturing care messages, including early learning, responsive caregiving, child nutrition, health, protection, and caregiver mental health. Group sessions are facilitated by a trained volunteer biweekly for a total of 11 months. The primary trial outcome is an overall measure of ECD using the Global Scales of Early Development long form version. Secondary outcomes include various caregiver outcomes (e.g., parenting practices, mental health) and other child outcomes (e.g., socioemotional development, dietary diversity). All outcomes will be assessed at baseline and endline. We will also conduct a qualitative implementation evaluation at endline and interview various stakeholders to assess program fidelity, quality, and sustainability.DiscussionThis trial will evaluate the effectiveness of a parenting intervention on ECD and caregiving outcomes and assess program implementation quality as delivered through existing community-based peer groups. This study will provide rigorous evidence that can be used to inform scale-up of this program model that leverages existing community social networks and resources for improving caregivers’ parenting skills and promoting ECD in rural Kenya and other similar settings across LMICs.Trial registrationClinicalTrials.gov #NCT06165315. Registered on December 11, 2023.

Real-world multidisciplinary outcomes of onasemnogene abeparvovec monotherapy in patients with spinal muscular atrophy type 1: experience of the French cohort in the first three years of treatment

BackgroundSpinal muscular atrophy type 1 (SMA1) is the most severe and early form of SMA, a genetic disease with motor neuron degeneration. Onasemnogene abeparvovec gene transfer therapy (GT) has changed the natural history of SMA1, but real-world data are scarce.MethodsA French national expert committee identified 95 newly diagnosed treatment-naive SMA1 patients between June 2019 and June 2022. We prospectively report on children treated with GT as the first and only therapy who had more than one-year of follow-up.ResultsForty-six SMA1 patients received GT. Twelve patients received other treatments. Patients with respiratory insufficiency were oriented toward palliative care after discussion with families. Twenty-nine of the treated patients with more than 12 months of follow-up were included in the follow-up analysis. Among them, 17 had 24 months of follow-up. The mean age at treatment was 7.5 (2.1–12.5) months. Twenty-two patients had two SMN2 copies, and seven had three copies. One infant died in the month following GT due to severe thrombotic microangiopathy, and another died due to respiratory distress. Among the 17 patients with 24 months of follow-up, 90% required spinal bracing (15/17), three patients required nocturnal noninvasive ventilation, and two needed gastrostomy. Concerning motor milestones at the 24-month follow-up, all patients held their head, 15/17 sat for 30 s unassisted, and 12/17 stood with aid. Motor scores (CHOPINTEND and HINE-2) and thoracic circumference significantly improved in all patients.ConclusionsOur study shows favorable motor outcomes and preserved respiratory and feeding functions in treatment-naive SMA1 infants treated by GT as the first and only therapy before respiratory and bulbar dysfunctions occurred. Nevertheless, almost all patients developed spinal deformities.

The role of Italian pre-participation screening in early detection of cardiomyopathies: what is the meaning of T wave inversion in young athletes?

The presence of T wave inversion on screening electrocardiogram may represent an early sign of cardiomyopathies in athletes. This finding even in very young athletes can generate some suspicion and may determine a contraindication to practice competitive sport. The aim of this study is to evaluate the prevalence of T wave inversion in a population of young competitive athletes and determine whether they can be associated with the occurrence of cardiomyopathies in the absence of other pathological features. A prospective cross-sectional study was carried out and 581 subjects were screened for competitive sport eligibility. Based on inclusion/exclusion criteria, 53 athletes showed T wave inversion and they were selected to undergo further investigations. In 32,1% of cases, we have identified the cause of T wave inversions and we suspended them from competition. In particular, in 15% of athletes who showed T wave inversions, we found cardiomyopathies. Prevalence of T wave inversion in this population of athletes was 9,1%. At the end of second and third-level evaluations, eight athletes with T wave inversion showed an early form of cardiomyopathy and were suspended from competitive sport. Most of them showed T wave inversion in infero-lateral leads on electrocardiogram. The probability that competitive athletes have a concealed cardiomyopathy is low, but not negligible. Pre-participation screening for competitive sport activity represents an excellent opportunity to early identify cardiomyopathies and other pathologies that increase the risk of sudden death in apparently healthy young athletes.

The Function of Cadres in Putting Child Development Stimulation, Detection, and Early Intervention Programs into Practice

The East Java province's child health care coverage in 2020 was 83.3%, a decrease from 2019. In Surabaya, the coverage in 2019 was 91.59%, but it still did not meet the 2020 Minimum Service Standards (MSS) target of 100%. The inadequate implementation of programs for early detection, stimulation, and intervention in child growth and development (SDIDTK) is one factor contributing to the failure to meet this objective. For these initiatives to be successful at the Posyandu level, community health workers, or cadres, must be involved. The objective of this research is to look at how the SDIDTK programs use cadres. There were 71 respondents in the cross-sectional research, which used an observational analytic methodology. Out of the seven roles, only two were performed by all cadres (71 individuals): determining head circumference, weight, height, and upper arm circumference; providing the information into the early detection form for assessing newborn growth and creating a visual representation of the results. In the mother and child health book, two roles were not performed by any of the cadres. The first responsibility was to complete the Early Detection of Child Growth and Development form by providing the child's identity. The second role was to use the child development checklist to observe and mark the child's developmental abilities as appropriate (√) or not appropriate (-).

Two birds, one story: Identifying the Exagoge’s mysterious bird

In the Hellenistic poem known as the Exagoge, Moses’ scouts, after discussing the oasis of Elim, describe a resplendent avian creature that is understood by most scholars today as the mythical Phoenix. A closer look at the arguments underpinning this identification reveals, however, numerous holes. This article presents a two-part argument, first to reveal the weaknesses of the arguments in support of the Phoenix, and then to propose an alternate solution to the identification: the bird known as the ortygometra (often erroneously identified simply as a quail). In the first half, the arguments of Howard Jacobson, who most vigorously defends the Phoenix identity, are evaluated, drawing mostly upon the work of an underappreciated article by Ben Zion Wacholder and Samuel Bowman. Once the weakness of these arguments is established and the alternative theory of the ortygometra proposed, the second half of the paper looks first at the history of the term “ortygometra” in Greek and Latin, from Aristotle through Augustine, revealing that the term was either collapsed into a synonym for “quail” or its identity was kept distinct. Following this is an analysis of the biblical quail narratives (in the MT, LXX, and Vulgate) and a selection of exegeses, which ultimately exposes the fluidity with which the story is treated by subsequent writings. In particular, the explanations found in the Wisdom of Solomon and the Pseudo-Augustinian text De mirabilibus Sacrae Scripturae demonstrate that the ortygometra had gathered more than a few “mythical” characteristics in its journey through tradition. Returning to the Exagoge with these insights yields a more satisfactory identity for the bird and potential witnesses to an early form of the “legendary ortygometra” tradition found in Wisdom and De mirabilibus.

토성의 등장과 축성기술의 형성

This paper examines the emergence of ancient earthen fortifications and the construction techniques that laid their foundations, under the premise that the appearance of ancient fortresses coincides with the formation of fortress construction techniques. Ancient fortresses first appeared as defensive structures characterized by walls and later evolved into significant political and administrative symbols for states. Among these, earthen fortifications, as suggested by the character ‘城’, represent an early form of such defensive walls, indicating a long-standing history. Literature records show that these fortifications existed prior to the Three Kingdoms period. Archaeological investigations of Bronze Age ditch enclosures indicate that the soil excavated from creating these enclosures was used to build earthen walls, which gradually developed into the defensive settlements known as earthen fortifications. In terms of the formation of construction techniques, the ability to build earthen fortifications likely did not emerge suddenly during the Three Kingdoms period. Constructing walls with soil requires appropriate techniques, specifically the technique of compaction, which means ‘to firmly pack soil.’ This compaction technique stemmed from accumulated civil engineering experiences since the Neolithic period and laid the groundwork for building earthen fortifications and other earthen structures. Recent findings of compaction marks in domestic earthen fortifications reveal that this technology had matured by the Three Kingdoms period. Therefore, it can be concluded that the practice of compacting soil began as early as the Neolithic period, evolving through the earthen walls of Bronze Age ditch enclosures into the form of fortifications. However, there remains a gap between the earthen walls of the Bronze Age and the construction of Three Kingdoms period fortifications. Future archaeological research is expected to further elucidate the emergence of these fortifications and the early techniques used in their construction.

Squamous Cell Carcinoma In Situ-The Importance of Early Diagnosis in Bowen Disease, Vulvar Intraepithelial Neoplasia, Penile Intraepithelial Neoplasia, and Erythroplasia of Queyrat.

Cutaneous squamous cell carcinoma (cSCC) is the second-most-prevalent malignancy in humans. A delayed diagnosis of cSCC leads to heightened invasiveness and positive surgical margins. Bowen's disease (BD) represents an early form of cSCC and presents as a small erythematous, photo-distributed, psoriasiform plaque. Although certain dermoscopy features in BD are quite characteristic, histopathology remains the gold standard for diagnosis and provides a severity-scoring system that assists in guiding appropriate treatment strategies. The classification of precancerous lesions of the vulva and penis has undergone multifarious transformations due to variations in clinical and histopathological characteristics. Presently, erythroplasia of Queyrat is categorized as a clinical variant of penile intraepithelial neoplasia (PeIN). The diagnoses of vulvar intraepithelial neoplasia (VIN) and PeIN present significant challenges and typically necessitate one or more biopsies, potentially guided by dermoscopy. Aceto-white testing demonstrates a notably high negative predictive value for genital precancerous lesions. Histopathological examination represents the gold-standard diagnosis in VIN and PeIN, while p16 and p53 immunostainings alongside HPV testing provide crucial diagnostic clues. The histopathologic features, degree of differentiation, and associations with lichen planus, lichen sclerosus, and HPV guide the selection of conservative treatments or surgical excision.

Doppler Positioning with LEO Mega-Constellation: Equation Properties and Improved Algorithm

Doppler positioning, as an early form of positioning, has regained significant research interest in the context of Low Earth Orbit (LEO) satellites.Given the LEO mega-constellation scenario, the objective function of Doppler positioning manifests significant nonlinearity, leading to ill-conditioning challenges for prevalent algorithms like iterative least squares (LS) estimation, especially in cases where inappropriate initial values are selected. In this study, we investigate the causes of ill-posed problems from two perspectives. Firstly, we analyze the linearization errors of the Doppler observation equations in relation to satellite orbital altitude and initial value errors, revealing instances where traditional algorithms may fail to converge. Secondly, from an optimization theory perspective, we demonstrate the occurrence of convergence to locally non-unique solutions for Doppler positioning. Subsequently, to address these ill-conditioning issues, we introduce Tikhonov regularization terms in the objective function to constrain algorithm divergence, with a fitted model for the regularization coefficient. Finally, we conduct comprehensive simulation experiments in both dynamic and static scenarios to validate the performance of the proposed algorithm. On the one hand, when the initial values are set to 0, our algorithm achieves high-precision positioning, whereas the iterative LS fails to converge. On the other hand, in certain simulation scenarios, the iterative LS converges to locally non-unique solutions, resulting in positioning errors exceeding 50 km in the north and east directions, several hundred kilometers in the vertical direction, and velocity errors surpassing 120 m/s. In contrast, our algorithm demonstrates typical errors of a position error of 6.8462 m, velocity error of 0.0137 m/s, and clock drift error of 8.3746 × 10−6 s/s.This work provides an effective solution to the sensitivity issue of initial points in Doppler positioning and can serve as a reference for the algorithm design of Doppler positioning receivers with LEO mega-constellations.

Childhood sexual trauma and opioid use among older adults living with HIV

ABSTRACT Childhood sexual abuse (CSA) has been linked to substance use and substance use disorders in adulthood. However, there have been limited studies examining the relationship between CSA and opioid use among older adults living with HIV (OALH). Therefore, the aim of this study was to determine the association between CSA and opioid use among OALH (n = 91). Data were obtained from an HIV clinic population in South Carolina using paper-and-pen, and online questionnaires. CSA was operationalized using six questions from the Early Trauma Inventory-Self Report Form (Yes vs. No). Opioid use was self-report of the use of opioids including: heroin, fentanyl, Oxycontin, Vicodin, codeine, morphine (used vs. never used). Nested crude and multivariable logistic regression models adjusting for sociodemographic confounders were used to determine the association between CSA and opioid use. After adjusting for race, gender, age, and education, OALH who were CSA survivors were 21 times more likely to currently use opioids compared to OALH who were not exposed to CSA (adjusted OR: 21.1; 95% CI: 1.78–250.0). The association seen between CSA history and opioid use may be due to unresolved trauma among OALH. Trauma-informed interventions addressing CSA may help to reduce opioid use among OALH.

Assessing Severity and Need for Delivery in Early Onset Preeclampsia Before 32 Weeks of Gestation: a Delphi Consensus Procedure.

Preeclampsia is a potentially life-threatening hypertensive pregnancy disorder that carries an acute risk of an unfavorable outcome of the pregnancy but also has consequences for the long-term health of the mother. Women who develop the early form of pre-eclampsia before the 32nd week of pregnancy have the highest risk and are also the most difficult to treat. The severity of pre-eclampsia is not characterized uniformly in Germany, so that the indication for delivery is rather individualized. The aim of this study was to reach a consensus on parameters that could serve as criteria for describing the severity of pre-eclampsia based on the urgency of delivery. To this end, a Delphi procedure was used to present a scenario in which a woman was admitted for preeclampsia before 32 gestational weeks and after completion of antenatal steroid therapy. Clinicians specialized in maternal-fetal medicine from German-speaking countries completed five rounds of a modified Delphi questionnaire. Presented parameters were selected by the section "Hypertensive Pregnancy Diseases and Fetal Growth Restriction" of the German Society of Gynecology and Obstetrics after reviewing the literature. These included objectifiable laboratory or clinical parameters as well as subjective symptoms of the patient. In addition, nine fetal parameters were taken into account. The clinicians were asked to rate presented parameters as an indication for delivery on a Likert scale from 0 to 4 (no indication to absolute indication without delay). For each item, the predefined cut-off for group consensus was ≥70% agreement. A total of 126 experts were approached. Sixty-nine experts (54.8%) took part in the first round; of those 50 completed the entire Delphi procedure. A consensus was reached on 14 parameters to be considered rapid preparation for delivery without delay (4 points on the Likert scale). These were among others hepatic hematoma or liver capsule rupture, acute liver failure with fulminant coagulation disorder or disseminated intravascular coagulation, eclampsia, pathologic findings in imaging (e.g. cMRI) or electrocardiogram arranged for new onset of headache or retrosternal pain, respectively. Twenty-six parameters were rated as factors that should be considered in the decision without being absolute (1 to 3 points), and 13 parameters should have no influence on the decision to deliver (0 points). No consensus on severe hypertension as an indication for delivery could be reached for blood pressure values below 220/140mmHg. A consensus was reached on whether to deliver in preeclampsia typic clinical findings and symptoms. The results can serve as guidance for current clinical practice and for the definition of clinical endpoints in intervention studies. Nevertheless, the isolated criteria are a theoretical construction since the combined deterioration or summation of several factors rather than a single factor most likely influences the decision to deliver and reflect the severity of preeclampsia. Moreover, the degree of hypertension as an indication for delivery remains controversial, unless the patient suffers additionally from complaints. Future research should be enforced to incorporate long-term risks for the mother into a decision aid.

Early Childhood Onset Vanishing White Matter Disease with Multiple Cranial Nerve Enhancement: A New Consensus Criteria?

Vanishing White Matter Disease (VWM), also known as Childhood Ataxia with Central Nervous System Hypomyelination (CACH), although a rare neurological condition, is a prevalent hereditary leukoencephalopathy with a characteristic phenotype of gradual neurologic deterioration with ataxia being a prominent feature. It is characterized by a wide range of onset, from antenatal and infantile periods to early childhood and later adulthood periods. The early childhood form is considered the prevailing form, characterized by a preceding phase of normal development until the second or 3rd year of life, followed by progressive neurologic deterioration, accentuated by certain stressors, such as infections or minor trauma. Diagnosis is achieved based on the clinical pretext combined with distinctive MRI brain features, confirmed by DNA analysis detection of elf2B mutation. Our case is a healthy 18-month-old male who after a preceding upper respiratory tract infection, developed an ataxic gait, encephalopathy, and recurrent generalized seizures. Physical assessment revealed signs of generalized spasticity and hyperreflexia. Neuroimaging revealed diffuse symmetric supratentorial and infratentorial diffuse white matter hypomyelination. Interestingly, there was notable enhancement of the 3rd and 5th cranial nerves. Differential diagnosis included acute demyelinating leukoencephalopathies; and neuromatobolic disorders with acute presentations (including leukodystrophies, hypomyelinating disorders, and mitochondrial encephalopathies). In the early course of his management, he received immunomodulatory therapy in the form of pulse steroids, intravenous immunoglobulins, and oral tapering course of steroids. He had limited response to these interventions. Whole exome sequencing yielded a homozygous mutation in EIF2B3, confirming the diagnosis of VWMD/CACH. The presence of enhancing cranial neuropathies represent an atypical phenotype reported in other case reports and should alert the physician to avoid unnecessary intervention with immunosuppressive therapies.

Repeated plague infections across six generations of Neolithic Farmers

In the period between 5,300 and 4,900 calibrated years before present (cal. bp), populations across large parts of Europe underwent a period of demographic decline1,2. However, the cause of this so-called Neolithic decline is still debated. Some argue for an agricultural crisis resulting in the decline3, others for the spread of an early form of plague4. Here we use population-scale ancient genomics to infer ancestry, social structure and pathogen infection in 108 Scandinavian Neolithic individuals from eight megalithic graves and a stone cist. We find that the Neolithic plague was widespread, detected in at least 17% of the sampled population and across large geographical distances. We demonstrate that the disease spread within the Neolithic community in three distinct infection events within a period of around 120 years. Variant graph-based pan-genomics shows that the Neolithic plague genomes retained ancestral genomic variation present in Yersinia pseudotuberculosis, including virulence factors associated with disease outcomes. In addition, we reconstruct four multigeneration pedigrees, the largest of which consists of 38 individuals spanning six generations, showing a patrilineal social organization. Lastly, we document direct genomic evidence for Neolithic female exogamy in a woman buried in a different megalithic tomb than her brothers. Taken together, our findings provide a detailed reconstruction of plague spread within a large patrilineal kinship group and identify multiple plague infections in a population dated to the beginning of the Neolithic decline.

History and philosophy of geography: Looking back and looking forward

This introduction to the special issue Reflections on Histories and Philosophies of Geography discusses the context and content of nineteen articles written to mark the fortieth anniversary of the History and Philosophy of Geography Research Group (HPGRG) of the Royal Geographical Society with the Institute of British Geographers (RGS-IBG). The group was founded in 1981, two years after the early career researchers who set up the group, Richard T. Harrison and David N. Livingstone, published jointly their first critical interventions in support of human geography's paradigmatic shift away from positivism, based on an early form of social constructivist argumentation. We argue that the subsequent proliferation of epistemic pluralism, which is discussed in the contributions to this special issue and has characterised the activities organised by the HPGRG, exemplifies the considerable value of three historiographical practices: first, engaging with the history and philosophy of geography collectively in one research group; second, situating methodologies within the history and philosophy of geography; and third, critically interrogating the discipline's evolving geographical knowledges, professional practices, and material cultures from different authorial positionalities.