Early Natural History Research Articles

An International Retrospective Early Natural History Study of LAMA2-Related Dystrophies.

LAMA2-related dystrophies (LAMA2-RDs) represent one of the most common forms of congenital muscular dystrophy and have historically been classified into two subtypes: complete or partial deficiency of laminin-211 (merosin). Patients with LAMA2-RD with the typical congenital phenotype manifest severe muscle weakness, delayed motor milestones, joint contractures, failure to thrive, and progressive respiratory insufficiency. While a comprehensive prospective natural history study has been performed in LAMA2-RD patients over 5 years of age, the early natural history of patients with LAMA2-RD 5 years and younger has not been comprehensively characterized. We extracted retrospective data for patients with LAMA2-RD ages birth through 5 years via the Congenital Muscle Disease International Registry (CMDIR). We analyzed the data using a phenotypic classification based on maximal motor milestones to divide patients into two phenotypic groups: "Sit" for those patients who attained that ability to remain seated and "Walk" for those patients who attained the ability to walk independently by 3.5 years of age. Sixty patients with LAMA2-RD from 10 countries fulfilled the inclusion criteria. Twenty-four patients had initiated non-invasive ventilation by age 5 years. Hospitalizations during the first years of life were often related to respiratory insufficiency. Feeding/nutritional difficulties and orthopedic issues were commonly reported. Significant elevations of creatine kinase (CK) observed during the neonatal period declined rapidly within the first few months of life. This is the largest international retrospective early natural history study of LAMA2-RD to date, contributing essential data for understanding early clinical findings in LAMA2-RD which, along with the data being collected in international, prospective early natural history studies, will help to establish clinical trial readiness. Our proposed nomenclature of LAMA2-RD1 for patients who attain the ability to sit (remain seated) and LAMA2-RD2 for patients who attain the ability to walk independently is aimed at further improving LAMA2-RD classification.

Does surgical intervention alter the natural history of degenerative rotator cuff tears? Comparative analysis from a prospective longitudinal study

The natural history of rotator cuff tears often involves progressive pain development, tear enlargement, and advancing muscle fatty degeneration. Both surgery and conservative management have proven to be effective treatments. Our study purpose was to compare the short to mid-term effects of rotator cuff repair on shoulder function, progression of tear size, and muscle degeneration compared to controls with asymptomatic tears that developed pain and were managed nonoperatively. This comparative study consists of two separate longitudinal study arms. The control group consisted of asymptomatic degenerative cuff tears followed until pain development and then managed nonoperatively with continued surveillance. The surgical group consisted of subjects with degenerative tears that failed nonoperative treatment and underwent surgical intervention with a minimum of 2 years follow-up. Outcomes included VAS pain, ASES, AROM, strength, and ultrasonography. There were 83 controls and 65 surgical shoulders. The surgical group was younger at enrollment (58.9±5.3 yr vs. 61.2±7.8 yr, p=0.04). The median follow-up for control subjects after pain development was 5.1 years (IQR 3.6) and the median postoperative follow-up for the surgical group was 3.0 years (IQR 0.2). Baseline tear widths (median 14 mm, IQR 9 vs. 13 mm, IQR 8; p=0.45) and tear lengths (median 14 mm, IQR 13 vs. median 11 mm, IQR 8; p=0.06) were similar between the surgical group and controls. There were no differences in the baseline prevalence of fatty degeneration of the supraspinatus or infraspinatus muscles between groups (p=0.43 and p=0.58, respectively). At final follow-up, the surgical group demonstrated significantly lower VAS pain (0 [IQR 2] vs. 3.5 [IQR 4], p=0.0002), higher composite ASES (95 [IQR 13] vs. 65.8 [IQR 32], p=0.0002) and ADL scores (29 [IQR 4] vs. 22 [IQR 8], p=0.0002), greater abduction strength (69.6 N [SD 29] vs. 35.9 N [SD 29], p=0.0002), greater active forward elevation (155˚ [SD 8] vs. 142˚ [SD 28], p=0.002), greater active external rotation in abduction (mean 98.5˚, SD 12 vs. mean 78.2˚, SD 20; p=0.0002) compared to controls. Additionally, the prevalence of fatty muscle degeneration was lower in the surgical group for the supraspinatus and infraspinatus (25% vs. 41%, p=0.05; 17% vs. 34%, p=0.03; respectively). This prospective longitudinal study comparing a surgical cohort undergoing rotator cuff repair with a control group treated nonoperatively supports the notion that surgical intervention has the potential to alter the early natural history of degenerative rotator cuff disease. Patients in the surgical group demonstrated clinically relevant differences in pain and functional outcomes. Surgical intervention was protective against progressive muscle degeneration compared to nonoperative treatment.

A 3-year natural history of orthostatic blood pressure dysregulation in early Parkinson’s disease

In Parkinson’s disease (PD), cardiovascular dysautonomia accumulates with disease progression, but studies are lacking on the natural history behind each subtype except orthostatic hypotension. This study investigated the early natural history of orthostatic blood pressure (BP) subtypes in PD. Two hundred sixty-seven early PD patients were included. Their cardiovascular functions were assessed by head-up tilt-test and 123I-metaiodobenzylguanidine scintigraphy. All patients were classified as having supine hypertension (SH), orthostatic hypertension (OHT), delayed orthostatic hypotension (dOH), or orthostatic hypotension (OH) according to consensus criteria. The patients were assigned to one of three groups: extreme BP dysregulation (BPextreme), mild BP dysregulation (BPmild), and no BP dysregulation (BPnone) according to their orthostatic BP subtypes. The autonomic functions of 237 patients were re-assessed after approximately 3 years. Among initially enrolled subjects, 61.8% of the patients showed orthostatic BP dysregulation: 29.6% in the BPextreme group and 32.2% in the BPmild group. At follow-up, the BPextreme group increased in number, while the BPmild group diminished. Two-thirds of the initial BPextreme patients maintained their initial subtype at follow-up. In comparison, 40.7% of the initial BPmild patients progressed to the BPextreme group, and 32.4% and 14.7% of the initial BPnone group progressed to BPextreme and BPmild groups, respectively. Cardiac denervation was most severe in the BPextreme group, and a linear gradient of impairment was observed across the subtypes. In conclusion, various forms of positional BP dysregulation were observed during the early disease stage. SH and OH increased with disease progression, while OHT and dOH decreased, converting primarily to SH and/or OH.

Cystathionine Beta-Synthase Deficiency: Three Consecutive Cases Detected in 40 Days by Newborn Screening in Emilia Romagna (Italy) and a Comprehensive Review of the Literature.

Cysthiatonine beta-synthase (CBS) deficiency (CBSD) is an autosomal recessive rare disorder caused by variations on CBS that leads to impaired conversion of homocysteine (Hcy) to cystathionine. Marked hyperhomocysteinemia is the hallmark of the disease. The administration of pyridoxine, the natural cofactor of CBS, may reduce total plasma Hcy. Patient phenotype is classified on pyridoxine responsivity in two groups: pyridoxine-responsive and non-responsive patients. Ectopia lentis, bone deformities, developmental delay, and thromboembolism are the classic signs and symptoms of the disease. Early diagnosis and treatment impact patients' natural history. Therapy aims to lower promptly and maintain Hcy concentrations below 100 μmol/L. Depending on the patient's phenotype, the treatment goals could be obtained by the administration of pyridoxine and/or betaine associated with a methionine-restricted diet. CBSD could be diagnosed in the early days of life by expanded newborn screening (ENS), however, the risk of false negative results is not negligible. In Emilia-Romagna (Italy), during the first 10 years of screening experience, only three cases of CBSD identified have been diagnosed, all in the last two years (incidence 1:118,000 live births). We present the cases and a comprehensive review of the literature to emphasize the role of ENS for early diagnosis of CBSD and its potential pitfalls, reiterating the need for a more effective method to screen for CBSD.

Kesar doodh is my love-language <3

Kesar doodh1 is my love-language <3 Pinka Popsickle (bio) Keywords Pinka Popsickle, poetry, saffron Stranger, your hands hangingloose at your sides, don't // become you; they—of dark wood and dirty nails, belong on— pale gold thighs; lost in crippled fingers; and my Maggi (curled like curled fingers) in between pale gold thighs/ sighs/ size sighs/s∧Iz/ verb emit a long, deep audible breathsize/s∧Iz/ noun estimate or measure of a body's expansesays/seIz/ verb utter words Stranger, your lip hangingloose 'round your joint, doesn't // become you; it—of bruised plum tandoor meat, belongs to— mountain(s)peak moans, lost in craggy contours; and silver tongue (slurs like slurred speech) in between mountain-speak/ mountain's peaks/ mouth-in-speech [End Page 748] speak/spi:k/ verb say something to expresspeak/pi:k/ noun climax in Freytag's pyramidspeech/spi:t∫/ noun expression, usually censored in words Stranger, your dick hangingloose in your pants won't // become you; it—of piss-stench failed love belongs on— graffitti walls; lost in translations, slogans, nations; and narrations (twisted like twisted spines) in between pure gold lies/ guise/ gai-sguise/g∧Iz/ noun external form/ manner of presentation that conceals somethingguy/g∧I/ verb ridiculegai/g∧I/ गाय noun; transl. sacred cow Pinka Popsickle pinka popsickle/priyanka d`souza is an "artistorian" from Mumbai, India. In her academic and artistic practice, she works with crip time and protest in ecological reimaginings, Mughal miniatures, early modern natural history, and the concept of the ajai'b (wondrous/strange), particularly in imaginings of borderlands of nation-empires and as applied to anomalous/disabled bodies. She is a poet fellow at Zoeglossia '22, and has been an artist-in-residence at Delfina Foundation, London '21, and a Dara Shikoh Fellow '16. NOTE 1. transl. Saffron milk. Copyright © 2022 The Massachusetts Review, Inc.

FP.39 An international retrospective early natural history study of LAMA2-related dystrophies

<i>LAMA2</i>-related dystrophies (LAMA2-RDs), caused by recessively inherited mutations in the <i>LAMA2</i> gene, represent one of the most common forms of congenital muscular dystrophy and are characterized by a complete or partial deficiency of laminin-211 (merosin). Patients with LAMA2-RDs presenting congenitally typically have a phenotype of severe weakness, delayed motor milestones, failure to thrive and progressive respiratory insufficiency. While a comprehensive prospective natural history study has been performed in LAMA2-RD patients >5 years, the early natural history of patients with LAMA2-RD 5 years and younger has not been comprehensively characterized. Extracting data from the CMD international registry, we describe a cohort of 62 patients with LAMA2-RD from 10 countries. Data for ages birth-5 years was retrospectively collected from the medical records. Inclusion criteria required that the patients had either two causative <i>LAMA2</i> variants or one confirmed causative <i>LAMA2</i> variant and a supporting clinical phenotype. Initial analyses reveal key findings including significant elevations of creatine kinase during the neonatal period which declined rapidly within the first few months of life. The mean age of first recognition of abnormal brain white matter appearance on MRI was 12.0 months. The first report of failure to thrive was at a mean age of 23.4 months. Noninvasive ventilation was initiated in half the patients by 24 months of age. This data represents the largest multinational retrospective early natural history study of LAMA2-RD which provides data essential for understanding early clinical history, especially as international, prospective early natural history data collection is in progress. Promising therapies in preclinical development for LAMA2-RD may ameliorate the phenotype of LAMA2-RD, particularly when initiated early in the course of the disease, making the comprehensive understanding of early natural history of LAMA2-RD timely and of great importance.

Different human papillomavirus types share early natural history transitions in immunocompetent women.

Necessary stages of cervical carcinogenesis include acquisition of a carcinogenic human papillomavirus (HPV) type, persistence associated with the development of precancerous lesions, and invasion. Using prospective data from immunocompetent women in the Guanacaste HPV Natural History Study (NHS), the ASCUS-LSIL Triage Study (ALTS) and the Costa Rica HPV Vaccine Trial (CVT), we compared the early natural history of HPV types to inform transition probabilities for health decision models. We excluded women with evidence of high-grade cervical abnormalities at any point during follow-up and restricted the analysis to incident infections in all women and prevalent infections in young women (aged <30 years). We used survival approaches accounting for interval-censoring to estimate the time to clearance distribution for 20 529 HPV infections (64% were incident and 51% were carcinogenic). Time to clearance was similar across HPV types and risk classes (HPV16, HPV18/45, HPV31/33/35/52/58, HPV 39/51/56/59 and noncarcinogenic HPV types); and by age group (18-29, 30-44 and 45-54 years), among carcinogenic and noncarcinogenic infections. Similar time to clearance across HPV types suggests that relative prevalence can predict relative incidence. We confirmed that there was a uniform linear association between incident and prevalent infections for all HPV types within each study cohort. In the absence of progression to precancer, we observed similar time to clearance for incident infections across HPV types and risk classes. A singular clearance function for incident HPV infections has important implications for the refinement of microsimulation models used to evaluate the cost-effectiveness of novel prevention technologies.

Von Recklinghausen disease revealed by breast node: Case report

Neurofibromatosis causes various types of benign or malignant tumors of the central or peripheral nerves and often causes pigmented macules of the skin and sometimes other manifestations. We present a case of 29 years old patient diagnosed by neurofibromatosis manifested by breast lesion, at the beginning, the diagnosis was not clear, but after the anatomopalogist report von Recklinghausen disease was suspected and the patient was having all the criteria to confirm that. Recent scientific data support a possible association between breast cancer and NF1. It has been suggested that there may be genes that could interact with the NF1 gene, particularly in relation to the BRCA1 subset. They could share a common gene location (both NF1 and BRCA1 are on human chromosome 17q). Multiple cutaneous lesions in NF-1 may obscure breast lumps leading to delayed detection of cancer. Early onset, aggressive behavior and different natural history of these tumors require a specific approach to their detection and management.

The ‘Stronsay Beast’: testimony, evidence and authority in early nineteenth-century natural history

When an unknown sea creature was washed ashore on the Orkney Islands in September 1808, the Edinburgh anatomist John Barclay declared that this was the first solid scientific evidence for the existence of the ‘great sea snake’. The testimony of witnesses along with some of its preserved body parts were examined by both the Wernerian Natural History Society in Edinburgh and the surgeon and anatomist Everard Home in London. Contradicting Barclay's opinion, Home identified the creature as a decomposing basking shark. While Barclay took the testimony of the local witnesses largely on trust and accepted their interpretation of the Beast, Home discounted it and instead asserted his own expert authority to correctly interpret the evidence. Both made use of the preserved physical remains of parts of the creature in strikingly different ways: Barclay to support the accounts of the witnesses, Home to undermine them. The debate between the two anatomists has much to tell us about the uses of evidence and testimony in early nineteenth-century natural history, but also has broader resonances for the roles of evidence and authority in science that still remain relevant today.

Abstract 9320: Biological Sex as a Modifier of the Natural History of Dilated Cardiomyopathy

Introduction: Dilated cardiomyopathy (DCM) has a ~20% 5-year mortality rate. Understanding the impact of biological sex offers scope to improve outcomes. Objective: Investigate potential sex specific differences in the outcome of DCM. Methods: Prospective longitudinal observational cohort study of 604 patients (n=206 women, 398 men) with DCM confirmed by cardiac MRI. The median follow up for cardiovascular death, major heart failure and arrhythmic events was 3.9 years. Results: At baseline women had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less myocardial fibrosis and lower serum troponin concentrations (all p&lt;0.05, Table 1), with no difference in age at study enrolment or medication. Despite this favourable profile, within 2 years women had more primary outcome events than men (Figure) with Kaplan Meier estimates of 10.7% vs 5.1%; adjusted* hazard ratio 3.47, 95% CI 1.81 to 6.65, [*age, LVEF, troponin, LMNA , left atrial volume and myocardial fibrosis]. Between 2-5 years, men and women had similar outcomes (adjusted* HR 0.55; 0.17,1.78). An LVEF &lt;35% in men (HR 3.21, 1.67 to 6.18, C-statistic 0.647) but &lt;40% in women (HR 2.37, 1.05 to 5.36, C statistic 0.602) had the greatest discrimination for predicting outcome. Conclusions: Female sex is an adverse modifier of the early natural history of DCM. There is evidence for sex specific risk stratification thresholds. Sex should be considered a determining variable in DCM care.

The Apocalyptic Herbarium

AbstractAnselm Kiefer’s monumental Secret of the Ferns (2007) redirects the artist’s apocalyptic sensibility, honed in response to the Holocaust, to the slow violence of extinction. The installation adopts a foundational practice of early modern natural history: the herbarium’s preservation and presentation of dried, pressed plant specimens. It also mobilizes the symbolic associations of ferns, which Kiefer calls “the first plants” but which are reimagined in the gallery space as the last plants in a postapocalyptic future. The framed specimens hang in a massive hall, with two abandoned concrete bunkers spewing out coal in the center—an allusion to ferns as the source of fossil fuels. Coal appears again in the enigmatic charcoal inscriptions on the frames that allude to ferns’ rich associations with rituals of magic and transformation. The overall mood is of a temporality at the end of time, a proleptic elegy that anticipates the extinction of even the most common and resilient plants, and the human cultures associated with them. Transmuted from mnemonic device to vehicle of commemoration, Kiefer’s apocalyptic herbarium elicits grief and mourning—but also, perhaps, what Judith Butler has called “the transformative effect of loss.”

The Avian Sense for Beauty: A Posthumanist Perspective on the Bowerbird

This essay uses the bowerbird's practice of collecting and arranging decorative objects to attract a mate as a point of departure to question the humanist commitments of art history as a discipline, and to explore what establishing a posthumanist art history might involve. I look to Charles Darwin's concept of sexual selection and the questions that it raised regarding the evolutionary origins of human creative activity. I discuss early natural history illustrations of bowerbirds along with Darwinian anthropologies of art, which bring human and avian aesthetic practices into dialogue. Finally, I draw on Richard Prum's theories on aesthetic evolution, Elizabeth Grosz's posthumanist perspective on art's origins, the emerging discipline of multispecies ethnography, and Indigenous Papuan understandings of the bowerbird, to ask how art historians might begin to restore human animals to a larger ecology of creative beings.

Visible Labour? Productive Forces and Imaginaries of Participation in European Insect Studies, ca. 1680-1810*.

The practice of early modern natural history depended on the collective collecting activities of a great variety of people. Among them, artisans played a major role in acquiring and distributing knowledge about the natural world and they contributed significantly to the scholarly labour in natural history. This distributed labour was both acknowledged by contemporaries as well as hidden from sight, reflecting the period′s dominant norms for class and gender. By combining an interpretation of the visual representation of labour in European insect studies with an examination of written sources about natural history practices from about 1680 to 1810, this article decodes the often‐codified frontispieces and other more symbolic illustrations to offer new insights into the labour of natural history. Those who identified as scholars and artisans (or both) conceptualised their own intellectual and practical engagement with natural history within the semantic field of work. Some seemed to have even envisioned a new social role for academics as well as artisans. This article analyses the diversity of the “productive forces” in insect studies as they changed over time and it reconstructs what I will call the social imaginaries of participation.

Incidence of diabetes in South Asian young adults compared to Pima Indians

IntroductionSouth Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians...

Genetic spectrum and clinical early natural history of glucose-6-phosphate dehydrogenase deficiency in Mexican children detected through newborn screening

BackgroundGlucose-6-phosphate dehydrogenase deficiency (G6PDd) newborn screening is still a matter of debate due to its highly heterogeneous birth prevalence and clinical expression, as well as, the lack of enough knowledge on its natural history. Herein, we describe the early natural clinical course and the underlying GDPD genotypes in infants with G6PDd detected by newborn screening and later studied in a single follow-up center. G6PDd newborns were categorized into three groups: group 1: hospitalized with or without neonatal jaundice (NNJ); group 2: non-hospitalized with NNJ; and group 3: asymptomatic. Frequencies of homozygous UGT1A1*28 (rs34983651) genotypes among G6PDd patients with or without NNJ were also explored.ResultsA total of 81 newborns (80 males, one female) were included. Most individuals (46.9%) had NNJ without other symptoms, followed by asymptomatic (42.0%) and hospitalized (11.1%) patients, although the hospitalization of only 3 of these patients was related to G6PDd, including NNJ or acute hemolytic anemia (AHA). Nine different G6PDd genotypes were found; the G6PD A−202A/376G genotype was the most frequent (60.5%), followed by the G6PD A−376G/968C (22.2%) and the Union-Maewo (rs398123546, 7.4%) genotypes. These genotypes produce a wide range of clinical and biochemical phenotypes with significant overlapping residual enzymatic activity values among class I, II or III variants. Some G6PD A−202A/376G individuals had enzymatic values that were close to the cutoff value (5.3 U/g Hb, 4.6 and 4.8 U/g Hb in the groups with and without NNJ, respectively), while others showed extremely low enzymatic values (1.1 U/g Hb and 1.4 U/g Hb in the groups with and without NNJ, respectively). Homozygosity for UGT1A1*28 among G6PDd patients with (11.9%, N = 5/42) or without (10.3%, N = 4/39) NNJ did not shown significant statistical difference (p = 0.611).ConclusionWide variability in residual enzymatic activity was noted in G6PDd individuals with the same G6PD genotype. This feature, along with a documented heterogeneous mutational spectrum, makes it difficult to categorize G6PD variants according to current WHO classification and precludes the prediction of complications such as AHA, which can occur even with > 10% of residual enzymatic activity and/or be associated with the common and mild G6PD A−376G/968C and G6PD A−202A/376G haplotypes.

The cancer multiple: Producing and translating genomic big data into oncology care

This article provides an ethnographic account of how Big Data biology is produced, interpreted, debated, and translated in a Big Data-driven cancer clinical trial, entitled “Personalized OncoGenomics,” in Vancouver, Canada. We delve into epistemological differences between clinical judgment, pathological assessment, and bioinformatic analysis of cancer. To unpack these epistemological differences, we analyze a set of gazes required to produce Big Data biology in cancer care: clinical gaze, molecular gaze, and informational gaze. We are concerned with the interactions of these bodily gazes and their interdependence on each other to produce Big Data biology and translate it into clinical knowledge. To that end, our central research questions ask: How do medical practitioners and data scientists interact, contest, and collaborate to produce and translate Big Data into clinical knowledge? What counts as actionable and reliable data in cancer decision-making? How does the explicability or translatability of genomic Big Data come to redefine or contradict medical practice? The article contributes to current debates on whether Big Data engenders new questions and approaches to biology, or Big Data biology is merely an extension of early modern natural history and biology. This ethnographic account will highlight how genomic Big Data, which underpins the mechanism of personalized medicine, allows oncologists to understand and diagnose cancer in a different light, but it does not revolutionize or disrupt medical oncology on an institutional level. Rather, personalized medicine is interdependent on different styles of (medical) thought, gaze, and practice to be produced and made intelligible.

Abstract 17108: Natural History of Cardiomyopathy and Cardiac Stress Response in Young Dogs With Golden Retriever Muscular Dystrophy

Introduction: Duchenne muscular dystrophy (DMD) and the genetically homologous model, golden retriever muscular dystrophy (GRMD), are x-linked conditions that cause progressive muscle wasting and cardiomyopathy. We previously defined a late onset DMD-like dilated cardiomyopathy in adult GRMD dogs and aimed to extend that work to young dogs used for preclinical studies. The goal of this study was to characterize the early natural history and cardiac stress response of GRMD cardiomyopathy. Methods: A prospective imaging study was completed in 10 GRMD dogs and 8 age-matched normal littermates at 3, 6, and 12 months of age. Electrocardiography (ECG), echocardiography with speckle tracking, and cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and myocardial T1 mapping were assessed. In an effort to identify early subclinical evidence of cardiomyopathy, we conducted a dobutamine stress test in an additional subset of dogs (17 GRMD vs. 6 normal). Fractional shortening (FS) was assessed using echocardiography during dobutamine infusion (5-25 μg/kg/min) at 2 months of age, with follow up studies (4 GRMD vs. 6 normal) at 4.5 and 6 months. Results: Heart rate and ECG Q/R ratios (lead II, III, and aVF) were greater in GRMD dogs at 12 months (p&lt;0.04 for all), and PR interval was shortened at 6 months (p=0.02). No systolic functional differences were seen between GRMD and normal dogs using echocardiography. No differences in circumferential strain were seen. CMR left ventricular end-diastolic volume, end-systolic volume, and myocardial mass were smaller in GRMD dogs from 6 months onward (p=0.014, 0.008, and 0.0013). LGE and extracellular volume calculated from T1 mapping did not differ on CMR. A diminished inotropic response, shown by a lower increase of FS (ΔFS), was seen in GRMD dogs during the dobutamine stress test (beginning at a dose of 5 μg/kg/min, 13.9±4.8% vs. 21.8±3.0%, p=0.003) at 2 months of age but not at 4.5 and 6 months. Conclusions: We demonstrated ECG changes and heart size differences in GRMD dogs as early as 6-12 months of age. While cardiac function was preserved, the inotropic response to dobutamine stress was blunted in 2-month-old GRMD dogs, potentially providing an early subclinical marker for DMD therapeutic research.

The Early Natural History of SARS-CoV-2 Infection: Clinical Observations From an Urban, Ambulatory COVID-19 Clinic

In March 2020, weeks before the coronavirus disease 2019 (COVID-19) pandemic surge was predicted to arrive in Massachusetts, two of us (J.N.J., L.E.H.) designed an ambulatory clinic specifically to care for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). None of the hundreds of research reports published to date addressed caring for patients infected with SARS-CoV-2 in the ambulatory setting, and it became clear that one of the first challenges we faced was to gain an understanding of the typical presentation and early natural history of mild and moderate COVID-19 to guide our care during the pandemic.

Fantasmas de la ciencia española by Juan Pimentel

Reviewed by: Fantasmas de la ciencia española by Juan Pimentel Jaime Marroquín Arredondo Juan Pimentel. Fantasmas de la ciencia española. MARCIAL PONS, 2020. 416 PP. JUAN PIMENTEL PRESENTS US with a panoramic history of Spanish science, from the early sixteenth century to the present. Its leitmotif is an understanding of science as a ghostly and haunting activity in the context of Spanish culture, where science has been underrepresented and lacking in national and international recognition despite the abundant achievements of scientists from Spain over the centuries. To illustrate his argument, Pimentel makes good use of some of the most impressive scientific accomplishments in the history of Spain and Hispanic America. Chapter 1, "Espectro y avistamiento del Mar del Sur," studies the so-called discovery of the Pacific Ocean by Vasco Núñez de Balboa (1475–1519) and the subsequent first cartographic representation of the Americas' Pacific coast: the Carta portulana representando el Mar del Sur (1518), a cartographic milestone Pimentel finds "haunted" by the "ghosts" of the extinct Cueva people, particularly Ponquiaco, main cacique of the Panamanian coast; these Amerindian spectral presences accompany the "ghosts" of the Spanish, Portuguese, and Italian experts who helped demarcate and imagine a coast that included Dabaiba, a mythical golden city precursor of the most famous El Dorado. If native people of Darién and Veragua were responsible for a great deal of the geographical information gathered by the Núñez de Balboa expedition, the Indigenous presence in early modern Spanish science is even more haunting in the work of doctor Francisco Hernández de Toledo (ca. 1515–87). The author of the Historia natural de Nueva España is, along with Santiago Ramón y Cajal (1852–1934), the most famous of all Spanish men of science. Hernández tackled the unimaginable task of updating, perfecting, and completing the Natural History of Pliny with a natural history of the New World. In chapter 2, "Naturalezas de otro mundo," Pimentel relates Hernandez's massive project to an equally gigantic enterprise: the gathering of reliable geographical and naturalist information about Spain's overseas possessions by the Council of Indies in the 1570s. The most visible result of these efforts is the well-known Relaciones Geográficas de Indias (1579–85), of which Pimentel provides a beautiful example: the mestizo map of the Zapotec town of Macuilxochitl, where Indigenous informants provided the immense majority of the knowledge displayed, including their consciousness of the ecological changes brought about by Spanish presence in their lands. The [End Page 179] polyphonic knowledge included in the Relaciones de Indias and in Hernández's natural history became a ghostly presence in early modern science accounts as neither of these two massive works sponsored by the Council of Indies would be published for centuries. Nevertheless—and despite the tragic loss of all of its colored illustrations—the work of Hernández had considerable influence in the development of early modern natural history through new processes of selection, translation, appropriation, and misappropriation. In chapter 3, "La mirada del ángel," Pimentel dissects some of the interconnections between the emerging field of microscopic medicine and its artistic representation using techniques and conventions common to the Spanish baroque. Among the distinctive qualities of the famous Golden Age of Spanish arts are a refined retrenchment into an orthodox Catholic culture and an accompanying literary disenchantment with the vain concerns of this world. The baroque thus promoted a profoundly moral vision of the world, even at the dawn of "el irremediable ascenso de la tecnología y el materialismo" (137). Such a view remained an intrinsic part of cutting-edge scientific achievements such as the impressive Atlas anatómico (ca. 1689) of Crisóstomo Martínez (1638–ca. 1694), where masterful macroscopic and microscopic images of human bones documenting their growth are accompanied by common moral symbols of life and death, or sin. Like the majority of baroque art, this moralized anatomy helped sustain the Spanish political body. Pimentel demonstrates how a common way of coupling the emerging microscopic view of nature with the all-encompassing Catholic view of the world was through the analogy of the angel's gaze, capable of seeing both the...

Planting dwelling thinking. Natural history and philosophy in sixteenth-century European dried gardens

Abstract European dried gardens from the 16th century have been traditionally associated with the emergence of early modern botany and its relation to the traditional genre of pharmacopeias. This study reviews a sample of the 37 known exemplars of these bound collections and argues that the design and development of these herbaria or dried gardens (orti sicci), as they were also known, reveal a broader set of questions on nature and about the relationships of humans with the natural world than the ones with which they have been linked. Based on the evidence of a diverse corpus of dried gardens—some richly bound, others composed over recycled paper, some with copious annotations, others with a seemingly random layout and distribution of plants—, this paper argues for a comparative reading of these books as a corpus that contributed significantly to early modern natural history and philosophy.