An Investigation of the Physical Education Specialist in the Elementary School

Acting on the premise that the physical education program is a vital part of the elementary school curriculum, every elementary school should provide qualified leadership, proper facilities, and activities suited to the growth and development of the participants

The Agricultural Emergency in Iowa, IV. Iowa Farm Mortgage Situation

This is the fourth publication in the series dealing with the present agricultural emergency in Iowa. The three preceding circulars are: 1. The Situation Today. 2. The Causes of the Emergency. 3. The Voluntary Domestic Allotment Plan. The present circular contains a revision of data appearing in Current Economic Series Report No. 6, Farm Mortgage Debt in Iowa, issued in October, 1927, and now out of print. In addition, new data are presented and the statistical series are brought up to date, 1925 being the last year previously reported. The authors wish to acknowledge the assistance of George Westcott in collecting the information; the cooperation of county officers, and aid in preparation of the manuscript by members of the Agricultural Economics Department

The Agricultural Emergency in Iowa, IX. Farm Mortgage Foreclosures

Two facts on the mortgage situation need to be emphasized. In the first place, the majority of outstanding mortgages are first mortgages held by lending institutions with obligations to meet in the future that are based on these mortgages. In the second place, foreclosures are not a· new development. For the last 12 years in Iowa a steady liquidation has taken place. Yet 1 billion dollars of farm mortgages are still outstanding. What can be done? Without question every lender and borrower should be familiar with the recent Mortgage Moratorium Act, a copy of which is included in the Appendix. In addition, what is needed is the cooperative study and action of both debtors and creditors on income-raising proposals. Agitation between debtors and creditors by itself will not correct the maladjustment. Both parties, lenders as well as borrowers, are suffering from the same trouble, low farm income. This circular has been divided into two parts, the first dealing with foreclosure data, particularly as they relate to the period 1921-32, and the second with proposed solutions. The authors are indebted to the staff of the Agricultural Economics Department for help in the preparation of this report. This publication is the ninth in the series on the agricultural emergency in Iowa. The next circular will deal with alternative foreign trade policies

Corporate-owned land in Iowa

According to a recent survey, an area equal to 7 of the 99 counties in Iowa is now owned by corporations. In more precise terms, 7.2 percent of the farm land in the 54 counties studied was found to be owned by insurance companies, open and closed banks, Federal and joint stock land banks, investment companies and other corporations. This average of 7.2 percent does not convey a true picture, however, because of the wide variations existing. In the county with the most corporate-owned land, 21 percent is in the hands of corporations; in the county at the other extreme, less than 2 percent of the land is so held. There seems, in addition, to be a rather marked concentration of corporate holdings in the north and south central sections of the state. Holdings in the center of the state and along the western border are, with few exceptions, relatively scarce

Treatment of Medically Refractory Cancer Pain with a Combination of Intrathecal Neuromodulation and Neurosurgical Ablation: Case Series and Literature Review

Objective Up to 90% of patients with advanced cancer experience intractable pain. For these patients, oral analgesics are the mainstay of therapy, often augmented with intrathecal drug delivery. Neurosurgical ablative procedures have become less commonly used, though their efficacy has been well‐established. Unfortunately, little is known about the safety of ablation in the context of previous neuromodulation. Therefore, the aim of this study is to present the results from a case series in which patients were treated successfully with a combination of intrathecal neuromodulation and neurosurgical ablation. Design Retrospective case series and literature review. Setting Three institutions with active cancer pain management programs in the U nited S tates. Methods All patients who underwent both neuroablative and neuromodulatory procedures for cancer pain were surveyed using the visual analog scale prior to the first procedure, before and after a second procedure, and at long‐term follow‐up. Based on initial and subsequent presentation, patients underwent intrathecal morphine pump placement, cordotomy, or midline myelotomy. Results Five patients (2 male, 3 female) with medically intractable pain (initial VAS  = 10) were included in the series. Four subjects were initially treated with intrathecal analgesic neuromodulation, and 1 with midline myelotomy. Each patient experienced recurrence of pain ( VAS  ≥ 9) following the initial procedure, and was therefore treated with another modality (intrathecal, N = 1; midline myelotomy, N = 1; percutaneous radiofrequency cordotomy, N = 3), with significant long‐term benefit ( VAS 1–7). Conclusion In cancer patients with medically intractable pain, intrathecal neuromodulation and neurosurgical ablation together may allow for more effective control of cancer pain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108610/1/pme12481.pd

Diversification of bacterial genome content through distinct mechanisms over different timescales

Bacterial populations often consist of multiple co-circulating lineages. Determining how such population structures arise requires understanding what drives bacterial diversification. Using 616 systematically sampled genomes, we show that Streptococcus pneumoniae lineages are typically characterized by combinations of infrequently transferred stable genomic islands: those moving primarily through transformation, along with integrative and conjugative elements and phage-related chromosomal islands. The only lineage containing extensive unique sequence corresponds to a set of atypical unencapsulated isolates that may represent a distinct species. However, prophage content is highly variable even within lineages, suggesting frequent horizontal transmission that would necessitate rapidly diversifying anti-phage mechanisms to prevent these viruses sweeping through populations. Correspondingly, two loci encoding Type I restriction-modification systems able to change their specificity over short timescales through intragenomic recombination are ubiquitous across the collection. Hence short-term pneumococcal variation is characterized by movement of phage and intragenomic rearrangements, with the slower transfer of stable loci distinguishing lineages

Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone

Background: Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain6B-2) clone of Streptococcus pneumoniae. Results: Whole genome sequencing of an international collection of 189 isolates estimated that PMEN2 emerged around the late 1960s, developing resistance through multiple homologous recombinations and the acquisition of a Tn5253-type integrative and conjugative element (ICE). Two distinct clades entered Iceland in the 1980s, one of which had acquired a macrolide resistance cassette and was estimated to have risen sharply in its prevalence by coalescent analysis. Transmission within the island appeared to mainly emanate from Reykjavík and the Southern Peninsular, with evolution of the bacteria effectively clonal, mainly due to a prophage disrupting a gene necessary for genetic transformation in many isolates. A subsequent decline in PMEN2’s prevalence in Iceland coincided with a nationwide campaign that reduced dispensing of antibiotics to children in an attempt to limit its spread. Specific mutations causing inactivation or loss of ICE-borne resistance genes were identified from the genome sequences of isolates that reverted to drug susceptible phenotypes around this time. Phylogenetic analysis revealed some of these occurred on multiple occasions in parallel, suggesting they may have been at least temporarily advantageous. However, alteration of ‘core’ sequences associated with resistance was precluded by the absence of any substantial homologous recombination events. Conclusions: PMEN2’s clonal evolution was successful over the short-term in a limited geographical region, but its inability to alter major antigens or ‘core’ gene sequences associated with resistance may have prevented persistence over longer timespans

Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients

On September 14–15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed

Development of DNA Damage Response Signaling Biomarkers using Automated, Quantitative Image Analysis

The DNA damage response (DDR) coordinates DNA repair with cell cycle checkpoints to ameliorate or mitigate the pathological effects of DNA damage. Automated quantitative analysis (AQUA) and Tissue Studio are commercial technologies that use digitized immunofluorescence microscopy images to quantify antigen expression in defined tissue compartments. Because DDR is commonly activated in cancer and may reflect genetic instability within the lesion, a method to quantify DDR in cancer offers potential diagnostic and/or prognostic value. In this study, both AQUA and Tissue Studio algorithms were used to quantify the DDR in radiation-damaged skin fibroblasts, melanoma cell lines, moles, and primary and metastatic melanomas. Digital image analysis results for three markers of DDR (γH2AX, P-ATM, P-Chk2) correlated with immunoblot data for irradiated fibroblasts, whereas only γH2AX and P-Chk2 correlated with immunoblot data in melanoma cell lines. Melanoma cell lines displayed substantial variation in γH2AX and P-Chk2 expression, and P-Chk2 expression was significantly correlated with radioresistance. Moles, primary melanomas, and melanoma metastases in brain, lung and liver displayed substantial variation in γH2AX expression, similar to that observed in melanoma cell lines. Automated digital analysis of immunofluorescent images stained for DDR biomarkers may be useful for predicting tumor response to radiation and chemotherapy

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial):A Multicentre, Randomised, Controlled Trial

RationaleMesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in COVID-19-related Acute Respiratory Distress Syndrome (ARDS).ObjectivesWe investigated safety and efficacy of ORBCEL-C (CD362-enriched, umbilical cord-derived MSCs) in COVID-related ARDS.MethodsThis multicentre, randomised, double-blind, allocation concealed, placebo-controlled trial (NCT03042143) randomised patients with moderate-to-severe COVID-related ARDS to receive ORBCEL-C (400million cells) or placebo (Plasma-Lyte148).MeasurementsThe primary safety and efficacy outcomes were incidence of serious adverse events and oxygenation index at day 7 respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2/FiO2 ratio and SOFA score. Clinical outcomes relating to duration of ventilation, length of intensive care unit and hospital stays, and mortality were collected. Long-term follow up included diagnosis of interstitial lung disease at 1 year, and significant medical events and mortality at 2 years. Transcriptomic analysis was performed on whole blood at day 0, 4 and 7.Main results60 participants were recruited (final analysis n=30 ORBCEL-C, n=29 placebo: 1 in placebo group withdrew consent). 6 serious adverse events occurred in the ORBCEL-C and 3 in the placebo group, RR 2.9(0.6-13.2)p=0.25. Day 7 mean[SD] oxygenation index did not differ (ORBCEL-C 98.357.2], placebo 96.667.3). There were no differences in secondary surrogate outcomes, nor mortality at day 28, day 90, 1 or 2 years. There was no difference in prevalence of interstitial lung disease at 1year nor significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome.ConclusionORBCEL-C MSCs were safe in moderate-to-severe COVID-related ARDS, but did not improve surrogates of pulmonary organ dysfunction. Clinical trial registration available at www.Clinicaltrialsgov, ID: NCT03042143. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)