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1.
Phys Rev Lett ; 132(14): 142502, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38640383

ABSTRACT

A precision measurement of the ß^{+} decay of ^{8}B was performed using the Beta-decay Paul Trap to determine the ß-ν angular correlation coefficient a_{ßν}. The experimental results were combined with new ab initio symmetry-adapted no-core shell-model calculations to yield the second-most precise measurement from Gamow-Teller decays, a_{ßν}=-0.3345±0.0019_{stat}±0.0021_{syst}. This value agrees with the standard model value of -1/3 and improves uncertainties in ^{8}B by nearly a factor of 2. By combining results from ^{8}B and ^{8}Li, a tight limit on tensor current coupling to right-handed neutrinos was obtained. A recent global evaluation of all other precision ß decay studies suggested a nonzero value for right-handed neutrino coupling in contradiction with the standard model at just above 3σ. The present results are of comparable sensitivity and do not support this finding.

2.
Future Oncol ; 20(3): 145-158, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37609795

ABSTRACT

Biosimilars can provide choices for patients and may provide cost savings; however, their uptake has been slow in the USA, in part due to limited knowledge. To provide additional confidence in US pegfilgrastim biosimilars, this narrative review compared the safety profiles of biosimilar pegfilgrastims, currently approved or filed for approval in the USA, with the EU- and US-approved reference pegfilgrastims. Headache and bone pain were common to biosimilars and reference products and occurred at a similar incidence. Clinical trial data on the safety profiles of biosimilar pegfilgrastims and reference products have demonstrated similarity and comparability, with no unexpected safety outcomes. Overall, the safety profiles of biosimilar pegfilgrastims and reference pegfilgrastims demonstrated a high degree of similarity and comparability.


Pegfilgrastim is a biologic drug (one made in living cells such as bacteria) that is given to some patients being treated for cancer. Pegfilgrastim is prescribed to reduce a patient's risk of infection due to a weakened immune system caused by various chemotherapy treatment plans. A biosimilar is a type of biologic medicine that is highly similar to a US FDA-approved reference biologic, and is often cheaper, making it more widely available to patients. As of March 2023, there are eight pegfilgrastim biosimilars (six approved and two awaiting approval by the FDA). This review compared the side effects for the reference pegfilgrastim with the biosimilar pegfilgrastims. The side effects in general and the side effects from treatment were similar for the reference pegfilgrastim and for the biosimilar pegfilgrastims, with the most common side effects being headache and bone pain. Serious side effects such as allergic reactions or problems with the spleen were very low and were also similar between the reference pegfilgrastim and the biosimilar pegfilgrastims. These results show that the safety of the biosimilar pegfilgrastims was similar to the reference pegfilgrastim, with no unexpected side effects. With comparable safety to their reference product, biosimilars have the potential to improve patient access to more affordable treatment options.


Subject(s)
Biosimilar Pharmaceuticals , Humans , Biosimilar Pharmaceuticals/adverse effects , Filgrastim/adverse effects , Polyethylene Glycols/adverse effects , Leukocytes
3.
Phys Rev Lett ; 131(26): 262701, 2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38215364

ABSTRACT

Nuclear isomer effects are pivotal in understanding nuclear astrophysics, particularly in the rapid neutron-capture process where the population of metastable isomers can alter the radioactive decay paths of nuclei produced during astrophysical events. The ß-decaying isomer ^{128m}Sb was identified as potentially impactful since the ß-decay pathway along the A=128 isobar funnels into this state bypassing the ground state. We report the first direct mass measurements of the ^{128}Sb isomer and ground state using the Canadian Penning Trap mass spectrometer at Argonne National Laboratory. We find mass excesses of -84564.8(25) keV and -84608.8(21) keV, respectively, resulting in an excitation energy for the isomer of 43.9(33) keV. These results provide the first key nuclear data input for understanding the role of ^{128m}Sb in nucleosynthesis, and we show that it will influence the flow of the rapid neutron-capture process.

4.
Phys Rev Lett ; 128(20): 202502, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35657880

ABSTRACT

The electroweak interaction in the standard model is described by a pure vector-axial-vector structure, though any Lorentz-invariant component could contribute. In this Letter, we present the most precise measurement of tensor currents in the low-energy regime by examining the ß-ν[over ¯] correlation of trapped ^{8}Li ions with the Beta-decay Paul Trap. We find a_{ßν}=-0.3325±0.0013_{stat}±0.0019_{syst} at 1σ for the case of coupling to right-handed neutrinos (C_{T}=-C_{T}^{'}), which is consistent with the standard model prediction.

5.
Anaesthesia ; 76(2): 225-237, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33289066

ABSTRACT

We convened a multidisciplinary Working Party on behalf of the Association of Anaesthetists to update the 2011 guidance on the peri-operative management of people with hip fracture. Importantly, these guidelines describe the core aims and principles of peri-operative management, recommending greater standardisation of anaesthetic practice as a component of multidisciplinary care. Although much of the 2011 guidance remains applicable to contemporary practice, new evidence and consensus inform the additional recommendations made in this document. Specific changes to the 2011 guidance relate to analgesia, medicolegal practice, risk assessment, bone cement implantation syndrome and regional review networks. Areas of controversy remain, and we discuss these in further detail, relating to the mode of anaesthesia, surgical delay, blood management and transfusion thresholds, echocardiography, anticoagulant and antiplatelet management and postoperative discharge destination. Finally, these guidelines provide links to supplemental online material that can be used at readers' institutions, key references and UK national guidance about the peri-operative care of people with hip and periprosthetic fractures during the COVID-19 pandemic.


Subject(s)
Case Management/standards , Hip Fractures/therapy , Anesthesia/standards , COVID-19 , Guidelines as Topic , Hip Fractures/surgery , Humans , Pandemics , Quality Improvement
6.
Oncologist ; 24(12): e1409-e1416, 2019 12.
Article in English | MEDLINE | ID: mdl-31420467

ABSTRACT

BACKGROUND: This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein (Hsp) 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). METHODS: Patients were randomized 1:1 to Arm A (carboplatin/pemetrexed plus apatorsen) or Arm B (carboplatin/pemetrexed plus placebo). Treatment was administered in 21-day cycles, with restaging every two cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and during treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, and toxicity. RESULTS: The trial enrolled 155 patients (median age 66 years; 44% Eastern Cooperative Oncology Group performance status 0). Toxicities were similar in the 2 treatment arms; cytopenias, nausea, vomiting, and fatigue were the most frequent treatment-related adverse events. Median PFS and OS were 6.0 and 10.8 months, respectively, for Arm A, and 4.9 and 11.8 months for Arm B (differences not statistically significant). Overall response rates were 27% for Arm A and 32% for Arm B. Sixteen patients (12%) had high serum levels of Hsp27 at baseline. In this small group, patients who received apatorsen had median PFS of 10.8 months, and those who received placebo had median PFS 4.8 months. CONCLUSION: The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting. IMPLICATIONS FOR PRACTICE: This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Oligonucleotides/therapeutic use , Pemetrexed/therapeutic use , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carboplatin/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Double-Blind Method , Female , Humans , Male , Neoplasm Staging , Oligonucleotides/pharmacology , Pemetrexed/pharmacology
7.
Eur Biophys J ; 48(2): 119-129, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30474716

ABSTRACT

The large number of potential applications of ionic liquids (ILs) requires an understanding of their environmental impacts including their adverse effects on microorganisms living in soil and water. The molecular mechanism of toxic activities of these liquids is yet to be understood in detail. Any foreign molecules, interacting with an organism, have to encounter first the cellular membrane, which is predominantly composed of the lipid bilayer. In this work, multilamellar vesicles (MLV) of phospholipids have been used to shed light on the effect of an IL on the structure of a cellular membrane. The MLVs formed by the zwitterionic lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) are found to shrink as a consequence of interaction with an imidazolium-based IL, 1-decyl-3-methylimidazolium tetrafluoroborate ([DMIM] [BF4]). The absorbed ILs significantly modify the surface charge of the MLVs. While these observations indicate a strong membrane-IL interaction, synchrotron-based small angle X-ray diffraction (SAXD) measurements provide a structural description of the interaction. SAXD and Fourier transform infrared spectroscopy studies clearly reveal a disordering effect of the IL on the conformational organization of the lipid chains. The presence of the negatively charged lipid 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine sodium salt (DPPS) in MLVs plays an important role in disordering the chains in the membrane and inter-bilayer interactions.


Subject(s)
Cell Membrane/chemistry , Ionic Liquids/chemistry , Membranes, Artificial , Phospholipids/chemistry , Temperature , Hydrodynamics , Imidazoles/chemistry , Lipid Bilayers/chemistry , Molecular Conformation
8.
J Oncol Pharm Pract ; 25(6): 1425-1433, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30924737

ABSTRACT

BACKGROUND: Lanreotide and octreotide acetate suspension for injectable (LAR) are both recommended for clinical use in patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors. However, each agent possesses unique attributes in terms of their drug-delivery characteristics. The study objective was to compare overall drug-delivery efficiency between lanreotide and octreotide LAR in gastroenteropancreatic neuroendocrine tumor patients. METHODS: This study employed an observational time and motion design among patients treated with lanreotide or octreotide LAR across five US cancer centers. Baseline patient data collection included age, disease grade and duration, prior therapies and performance status. Drug-delivery time (drug preparation and administration), total patient time and resource use data were collected for gastroenteropancreatic neuroendocrine tumors receiving lanreotide (n = 22) or octreotide LAR (n = 22). Following each administration, qualitative data on the drug-delivery experience was collected from patients and nurses. RESULTS: Lanreotide was associated with a significant reduction in mean delivery time (2.5 min; 95% CI:2.0 to 3.1) compared to octreotide LAR (6.2 min; 95%CI: 4.4 to 7.9; p = 0.004). The mean total patient time for lanreotide and octreotide LAR was comparable between groups (32.1 vs. 36.6 minutes; p = 0.97). Nurses reported increased concerns with octreotide LAR related to needle clogging (p = 0.034) and device failures (p = 0.057). Overall, lanreotide had a median satisfaction score of 5.0 compared to a score of 4.0 with octreotide LAR (p = 0.03). CONCLUSIONS: Lanreotide was associated with significant reductions in drug-delivery time compared to octreotide LAR, which contributed to an improvement in overall healthcare efficiency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03017690.


Subject(s)
Antineoplastic Agents/therapeutic use , Intestinal Neoplasms/drug therapy , Medication Systems/organization & administration , Neuroendocrine Tumors/drug therapy , Octreotide/therapeutic use , Pancreatic Neoplasms/drug therapy , Peptides, Cyclic/therapeutic use , Somatostatin/analogs & derivatives , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Attitude of Health Personnel , Drug Compounding , Equipment Failure , Female , Health Resources/statistics & numerical data , Humans , Injections , Male , Middle Aged , Needles/adverse effects , Patient Satisfaction , Prospective Studies , Somatostatin/therapeutic use , Time and Motion Studies
9.
J Dairy Sci ; 102(3): 2645-2656, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30692002

ABSTRACT

Estrus in dairy cattle varies in duration and intensity, highlighting the need for accurate and continuous monitoring to determine optimal breeding time. The objective of this study was to evaluate precision dairy monitoring technologies (PDMT) for detecting estrus. Estrus was synchronized in lactating Holstein cows (n = 109) using a modified G7G-Ovsynch protocol (last GnRH injection withheld to permit expression of estrus) beginning at 45 to 85 d in milk. Resumption of ovarian cyclicity at enrollment was verified by transrectal ultrasonography for presence of a corpus luteum. Cows were observed visually during 30 min (4 times per day) for behavioral estrus on d -1 to 2 (d 0 = day of estrus). Periods peri-estrus were defined by the temporal blood plasma progesterone patterns on d -5, -4, -3, -2, -1, 0, 2, 4, 6, and 8. Estrous detection by PDMT, an estrous behavior scoring system, and by visual observation of standing estrus were compared with the reference (gold) standard. Only 56% of cows that ovulated were observed standing by visual observation. Sensitivity and specificity for estrous detection were not different among all PDMT. Devices in this study measuring activity in steps, neck movement, high activity of head movement, or a proprietary motion index increased on the day of estrus 69 to 170% from the baseline before estrus. The change in rumination time on the day of estrus decreased for both neck and ear-based technologies (-2 to -16%). Temperature of the reticulorumen, vagina, and ear skin were not different on the day of estrus than day peri-estrus. Daily lying times decreased on average to 24.6% on the day of estrus for IceQube (IceRobotics Ltd., Edinburgh, Scotland). In contrast, lying time increased 15.5 and 33.1% for AfiAct Pedometer Plus (Afimilk, Kibbutz Afikim, Israel) and Track a Cow (ENGS Systems Innovative Dairy Solutions, Rosh Pina, Israel), respectively. All PDMT tested were capable of detecting estrus at least as effectively as visual observation. Four of the 6 PDMT that reported estrous alerts correctly detected 15 to 35% more cows than visual observation 4 times per day. Use of temporal progesterone patterns correctly identified more cows than visual observation alone. Dairy producers considering PDMT should focus on (1) the reference (gold) standard used to test efficacy of a device's alerts and (2) the device that will have the fewest false readings in their operations.


Subject(s)
Breeding/methods , Cattle/physiology , Dairying/methods , Estrus Detection/methods , Estrus Synchronization , Estrus/physiology , Animals , Behavior, Animal , Corpus Luteum/diagnostic imaging , Dinoprost/metabolism , Estrus Detection/instrumentation , Estrus Synchronization/methods , Female , Gonadotropin-Releasing Hormone/administration & dosage , Insemination, Artificial/veterinary , Lactation , Milk/metabolism , Ovulation , Progesterone/blood , Sensitivity and Specificity , Ultrasonography/veterinary
11.
J Immunol ; 195(10): 4685-98, 2015 Nov 15.
Article in English | MEDLINE | ID: mdl-26466956

ABSTRACT

Apolipoprotein (Apo)A-I, the major lipid-binding protein of high-density lipoprotein, can prevent autoimmunity and suppress inflammation in hypercholesterolemic mice by attenuating lymphocyte cholesterol accumulation and removing tissue-oxidized lipids. However, whether ApoA-I mediates immune-suppressive or anti-inflammatory effects under normocholesterolemic conditions and the mechanisms involved remain unresolved. We transferred bone marrow from systemic lupus erythematosus (SLE)-prone Sle123 mice into normal, ApoA-I-knockout (ApoA-I(-/-)) and ApoA-I-transgenic (ApoA-I(tg)) mice. Increased ApoA-I in ApoA-I(tg) mice suppressed CD4(+) T and B cell activation without changing lymphocyte cholesterol levels or reducing major ApoA-I-binding oxidized fatty acids. Unexpectedly, oxidized fatty acid peroxisome proliferator-activated receptor γ ligands 13- and 9-hydroxyoctadecadienoic acid were increased in lymphocytes of autoimmune ApoA-I(tg) mice. ApoA-I reduced Th1 cells independently of changes in CD4(+)Foxp3(+) regulatory T cells or CD11c(+) dendritic cell activation and migration. Follicular helper T cells, germinal center B cells, and autoantibodies were also lower in ApoA-I(tg) mice. Transgenic ApoA-I also improved SLE-mediated glomerulonephritis. However, ApoA-I deficiency did not have the opposite effects on autoimmunity or glomerulonephritis, possibly as the result of compensatory increases in ApoE on high-density lipoprotein. We conclude that, although compensatory mechanisms prevent the proinflammatory effects of ApoA-I deficiency in normocholesterolemic mice, increasing ApoA-I can attenuate lymphocyte activation and autoimmunity in SLE independently of cholesterol transport, possibly through oxidized fatty acid peroxisome proliferator-activated receptor γ ligands, and it can reduce renal inflammation in glomerulonephritis.


Subject(s)
Apolipoprotein A-I/metabolism , Autoimmunity/immunology , Cholesterol/metabolism , Lupus Nephritis/immunology , Lymphocyte Activation/immunology , Animals , Apolipoprotein A-I/genetics , Apolipoprotein A-I/immunology , Apolipoproteins E/metabolism , Autoantibodies/blood , Autoantibodies/immunology , Autoimmunity/genetics , B-Lymphocytes/immunology , Bone Marrow Transplantation , Cell Movement/immunology , Dendritic Cells/immunology , Gas Chromatography-Mass Spectrometry , Linoleic Acids/metabolism , Lipoproteins, HDL/immunology , Lupus Nephritis/genetics , Lupus Nephritis/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , PPAR gamma/metabolism , T-Lymphocytes, Regulatory/immunology , Th1 Cells/immunology
12.
Manag Care ; 26(9): 37-47, 2017 09.
Article in English | MEDLINE | ID: mdl-29068312

ABSTRACT

PURPOSE: The Oncology Care Model (OCM) is a payment model from the Centers for Medicare and Medicaid Services designed to reduce costs and improve quality in cancer care. Key components of quality for the OCM originate from the 13-component cancer care plan. We surveyed the literature to understand the value of prognosis in OCM-directed planning for non-small-cell lung cancer (NSCLC) care and to investigate how the results of a prognostic, proteomic biomarker test, the VeriStrat test, can help OCM-participating providers meet the specific quality measures. DESIGN: A targeted literature review was supplemented by real-world author experience. METHODOLOGY: Available MEDLINE-indexed literature on the topic of lung cancer prognosis and cancer care planning (1997-2017) were reviewed. Authors also included relevant commentary based on their own real-world experience with VeriStrat testing and prognostic conversations. RESULTS: There was near-universal consensus in guidelines and literature about the critical importance of early, candid, and ongoing physician-patient discussions about prognosis, which informs most components of the OCM care plan. The VeriStrat test has been shown to provide accurate predictions of outcomes in all lines of therapy and in various treatments for patients with NSCLC, including chemotherapies and EGFR-TKI therapies. CONCLUSION: Accurate prognostic estimates, such as those provided by the VeriStrat test, are useful for predicting and documenting expected response to treatment, avoiding ineffective and costly overtreatment and for facilitating meaningful conversations with NSCLC patients about the timing of best supportive care and hospice care when appropriate, thereby improving cancer care planning and quality scores.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Patient Care Planning , Prognosis , Proteomics , Quality Indicators, Health Care , Humans , Quality of Health Care
13.
Opt Express ; 24(16): 18209-16, 2016 Aug 08.
Article in English | MEDLINE | ID: mdl-27505785

ABSTRACT

We report the reflectance, ~1° from normal incidence, of six different mirrors as a function of photon energy, using monochromatic vacuum ultraviolet (VUV) and extreme ultraviolet (XUV) radiation with energies between 7.5 eV and 24.5 eV. The mirrors examined included both single and multilayer optical coatings, as well as an uncoated substrate. We discuss the performance of each mirror, paying particular attention to the potential application of suppression and selection of high-order harmonics of a Ti:sapphire laser.

14.
J Nurs Manag ; 24(3): 366-75, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26370219

ABSTRACT

AIMS: To explore the experiences of senior charge nurses provided with 'increased supervisory hours'. BACKGROUND: Designated supervisory time is essential for senior charge nurses to provide effective clinical leadership. It is important to explore the impact arises of such an increase. METHODS: An online questionnaire collected exploratory data from senior charge nurses (n = 60). Semi-structured interviews gathered in-depth qualitative data (n = 12). Findings were analysed for common themes associated with implementation of the increased senior charge nurse supervisory role. RESULTS: The majority of senior charge nurses were unable to use their full allocation of supervisory time. They struggled to accomplish leadership goals because of managing staffing levels, increased workload, time constraints and limited support. Factors that facilitated the role included preparation and support, adequate staff capacity, effective leadership skills and availability of supervisory time. The senior charge nurses took pride in providing clinical leadership, promoting staff development and delivering patient care. Support, in terms of preparation, capacity building and ongoing mentoring, was a key factor for achieving senior charge nurse goals. CONCLUSION: Senior charge nurses should be supported to maximise supervisory time through the provision of an induction programme, formal coaching and ongoing training and development. IMPLICATIONS FOR NURSING MANAGEMENT: Preparation and support is essential for senior charge nurses to deliver enhanced clinical leadership through increased supervisory time.


Subject(s)
Nurse's Role , Nursing Staff, Hospital/organization & administration , Nursing, Supervisory/organization & administration , Attitude of Health Personnel , Humans , Interviews as Topic , Qualitative Research , Surveys and Questionnaires , Time Factors , Workload
15.
Br J Surg ; 102(10): 1272-7, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26104685

ABSTRACT

BACKGROUND: The aim of this study was to investigate whether the increased mortality previously identified for surgery performed on Fridays was apparent following major elective colorectal resections and how this might be affected by case mix. METHODS: Patients undergoing elective colorectal resections in England from 2001 to 2011 were identified using Hospital Episode Statistics. Propensity scores were used to match patients having operations on a Friday in a 1 : 1 ratio with those undergoing surgery on other weekdays. Multivariable analyses were used to investigate overall deaths within 1 year of operation. RESULTS: A total of 204,669 records were extracted for patients undergoing major elective colorectal resections. Patients who had surgery on Fridays were more deprived (4780 (17.1 per cent) of 27,920 versus 28,317 (16.0 per cent) of 176,749; P < 0.001), a greater proportion had had an emergency admission in the 3 previous months (7870 (28.2 per cent) of 27,920 versus 48,623 (27.5 per cent) of 176,749; P = 0.019), underwent minimal access surgery (4565 (16.4 per cent) of 27,920 versus 23,783 (13.5 per cent) of 176,749; P < 0.001) and had surgery for benign diagnoses (6502 (23.3 per cent) of 27,920 versus 38,725 (21.9 per cent) of 176,749; P < 0.001) than those who had surgery on Mondays to Thursdays. In a matched analysis the odds ratio for 30-day mortality after colorectal resections performed on Fridays compared with other weekdays was 1.25 (95 per cent c.i. 1.13 to 1.37); odds ratios for 90-day and 1-year mortality were 1.16 (1.07 to 1.25) and 1.10 (1.04 to 1.16) respectively. CONCLUSION: Patients selected for colorectal resections on Fridays had a higher mortality rate than patients operated on from Monday to Thursday and had different characteristics, suggesting that increased mortality may reflect patient factors rather than hospital variables alone.


Subject(s)
Colorectal Neoplasms/mortality , Elective Surgical Procedures/methods , Hepatectomy/methods , Adolescent , Adult , Aged , Colorectal Neoplasms/surgery , England/epidemiology , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Male , Middle Aged , Postoperative Period , Retrospective Studies , Risk Factors , Survival Rate/trends , Time Factors , Young Adult
16.
Phys Rev Lett ; 114(21): 217202, 2015 May 29.
Article in English | MEDLINE | ID: mdl-26066455

ABSTRACT

We use particle-based simulations to examine the static and driven collective phases of Skyrmions interacting with random quenched disorder. We show that nondissipative effects due to the Magnus term reduce the depinning threshold and strongly affect the Skyrmion motion and the nature of the dynamic phases. The quenched disorder causes the Hall angle to become drive dependent in the moving Skyrmion phase, while different flow regimes produce distinct signatures in the transport curves. For weak disorder, the Skyrmions form a pinned crystal and depin elastically, while for strong disorder the system forms a pinned amorphous state that depins plastically. At high drives the Skyrmions can dynamically reorder into a moving crystal, with the onset of reordering determined by the strength of the Magnus term.

17.
Br J Dermatol ; 173(3): 690-700, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25712143

ABSTRACT

BACKGROUND: Glucocorticoids (GCs) are first-line treatment for keloid disease (KD) but are limited by high incidence of resistance, recurrence and undesirable side-effects. Identifying patient responsiveness early could guide therapy. METHODS: Nineteen patients with KD were recruited at week 0 (before treatment) and received intralesional steroids. At weeks 0, 2 and 4, noninvasive imaging and biopsies were performed. Responsiveness was determined by clinical response and a significant reduction in vascular perfusion following steroid treatment, using full-field laser perfusion imaging (FLPI). Responsiveness was also evaluated using (i) spectrophotometric intracutaneous analysis to quantify changes in collagen and melanin and (ii) histology to identify changes in epidermal thickness and glycosaminoglycan (GAG) expression. Biopsies were used to quantify changes in glucocorticoid receptor (GR) expression using quantitative reverse transcriptase polymerase chain reaction, immunoblotting and immunohistochemistry. RESULTS: At week 2, the FLPI was used to separate patients into steroid responsive (n = 12) and nonresponsive groups (n = 7). All patients demonstrated a significant decrease in GAG at week 2 (P < 0.05). At week 4, responsive patients exhibited significant reduction in melanin, GAG, epidermal thickness (all P < 0.05) and a continued reduction in perfusion (P < 0.001) compared with nonresponders. Steroid-responsive patients had increased GR expression at baseline and showed autoregulation of GR compared with nonresponders, who showed no change in GR transcription or protein. CONCLUSIONS: This is the first demonstration that keloid response to steroids can be measured objectively using noninvasive imaging. FLPI is a potentially reliable tool to stratify KD responsiveness. Altered GR expression may be the mechanism gating therapeutic response.


Subject(s)
Keloid/drug therapy , Receptors, Glucocorticoid/metabolism , Steroids/therapeutic use , Adult , Analysis of Variance , Cicatrix/metabolism , Cicatrix/pathology , Female , Humans , Immunohistochemistry , Keloid/pathology , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Treatment Outcome , Young Adult
18.
Int J Legal Med ; 129(4): 771-5, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25904080

ABSTRACT

Gabapentin (GBP) (Neurontin®, Horizant®, Gralise®) is a widely prescribed medication used primarily for the treatment of epilepsy and neuropathic pain. GBP has a favorable adverse effect profile in therapeutic dosing with the most common reported effects being dizziness, fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional GBP self-poisonings, serious effects are rare. A 47-year-old female was found dead at work with her daughter's bottle of GBP 600 mg. There were 26 tablets missing and the decedent's only known medication was hydrocodone/acetaminophen. Following initial detection by an alkaline drug screen (GC-MS), analysis utilizing specific liquid chromatography-mass spectrometry revealed an elevated postmortem GBP peripheral blood concentration of 37 mg/L, central blood 32 mg/L, liver 26 mg/kg, vitreous 32 mg/L, and gastric contents 6 mg. Screening for volatiles, drugs of abuse, alkaline compounds, and acid/neutral compounds was negative with the exception of ibuprofen (<2 mg/L) detected in peripheral blood. This report presents a fatality that appears to be associated with an isolated and acute GBP ingestion.


Subject(s)
Amines/poisoning , Analgesics/poisoning , Cyclohexanecarboxylic Acids/poisoning , gamma-Aminobutyric Acid/poisoning , Amines/analysis , Analgesics/analysis , Cardiovascular Diseases , Chromatography, Liquid , Cyclohexanecarboxylic Acids/analysis , Female , Gabapentin , Gas Chromatography-Mass Spectrometry , Gastrointestinal Contents/chemistry , Humans , Liver/chemistry , Middle Aged , Obesity , Vitreous Body/chemistry , gamma-Aminobutyric Acid/analysis
19.
Indian J Med Res ; 141(1): 62-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25857496

ABSTRACT

BACKGROUND & OBJECTIVES: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS) patients. METHODS: Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR) was used for insulin resistance. The fasting serum total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC) of the receiver operating characteristic (ROC) curves were used to compare the power of these serum lipoprotein ratios as markers. RESULTS: Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05). Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05). The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93), 0.78 (95% CI, 0.65 to 0.91), respectively. INTERPRETATION & CONCLUSIONS: The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.


Subject(s)
Acute Coronary Syndrome/blood , Biomarkers/blood , Blood Glucose/metabolism , Cholesterol, HDL/blood , Fasting , Insulin Resistance , Triglycerides/blood , Diabetes Mellitus , Female , Humans , Male , Middle Aged
20.
J Dairy Sci ; 98(6): 4206-10, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25841963

ABSTRACT

The objective of this study was to describe the differences in freestall cleanliness and stall temperature between a barn with Dual Chamber Cow Waterbeds (DCCW; Advanced Comfort Technology, Reedsburg, WI) and a barn with rubber-filled mattresses at the University of Kentucky Coldstream Dairy Research Farm from January 18, 2012, to May 3, 2013. Stall cleanliness was measured twice weekly (n=134) by the same 2 observers using a 0.91 m×0.91 m wire grid containing 128 equally sized rectangles (10.16 cm×5.08 cm). This grid was centered at the rear portion of the stall; a rectangle that was visibly wet or had any amount of feces present was defined as a dirty rectangle. Weekly stall temperature (n=66) was measured by the same observer during a.m. milkings in the same predetermined stalls. Feces and wet sawdust were removed from the stalls before stall temperatures were acquired. Temperatures were obtained using a handheld thermometer at 30.48 cm above the stall base as determined via dual laser measurements. Stall temperature was measured on the front, middle, and back of the stall first with clean sawdust and then with the sawdust removed from the stall and wiped clean with a towel. Daily temperature-humidity index (THI) was calculated using Kentucky climate data calculated through the University of Kentucky College of Agriculture via a data logger, located 5.63 km from the Coldstream Dairy Farm. Stall cleanliness was not different between the DCCW barn (26.09±0.89 rectangles) and the rubber-filled mattress barn (23.70±0.89 rectangles). Mean THI throughout the study was 64.39±0.82. Stall temperature was different among THI categories. Temperature-humidity index categories 1 (coldest), 2, 3, and 4 (warmest) had THI ranges of 22.94 to 50.77, 50.77 to 64.88, 64.88 to 78.75, and 78.75 to 101.59, respectively. Stall temperatures (°C; least squares means±SE) were 2.26±0.30, 8.86±0.30, 15.52±0.30, and 20.95±0.30 for THI categories 1 to 4, respectively. Stalls with rubber-filled mattresses had a lower temperature (°C) than DCCW with least squares means±SE of 10.52±0.21°C and 13.29±0.21°C, respectively. The DCCW were probably significantly warmer because water holds heat well. The DCCW may have more of a heat-insulating effect compared with rubber-filled mattresses.


Subject(s)
Dairying/methods , Housing, Animal , Animals , Cattle , Dairying/instrumentation , Female , Hygiene , Kentucky , Temperature
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