Classical guitar intonation and compensation: The well-tempered guitar.

An intuitive model of classical guitar intonation is presented that includes the effects of the resonant length of the fretted string, linear mass density, tension, and bending stiffness. An expression is derived for the vibration frequencies of a stiff string using asymmetric boundary conditions at the saddle and the fret. Based on logarithmic frequency differences ("cents") that decouple these physical effects, Taylor series expansions are introduced that exhibit clearly the origins of frequency deviations of fretted notes from the corresponding 12-tone equal temperament (12-TET) values. A simple in situ technique is demonstrated for measurement of the changes in frequency of open strings arising from small adjustments in length, and a simple procedure is proposed that any interested guitarist can use to estimate the corresponding frequency shifts due to tension and bending stiffness for their own guitars and string sets. Based on these results, a least-squares fit method is employed to select values of saddle and nut setbacks that map fretted frequencies-for a particular string set and guitar-almost perfectly onto their 12-TET targets. A general approach to tempering an "off-the-shelf" guitar is shown to further reduce the tonal errors inherent in any fretted musical instrument.

Luminescence characterization of BioGlass undoped and doped with europium and silver ions.

The objective of this study was to investigate the properties of BioGlass, with and without doping with europium and silver, with a specific focus on its potential application in thermoluminescent (TL) and optically stimulated luminescent (OSL) dosimetry. The structural and optical characteristics of the samples were also analyzed using techniques such as X-ray diffraction (XRD), optical absorption (OA), and fluorescence spectroscopy (FL). An XRD analysis confirmed the amorphous phase of the BioGlass. OA and FL spectra were obtained at room temperature, and characteristic bands of dopant ions were observed which confirmed the incorporation of the Eu3+ ions and silver nanoparticles Ag(NP) ion into the BioGlass. The OSL decay curves exhibited a characteristic exponential behavior, with a notable presence of fast and medium decay components; this suggests that the charge traps within the BioGlass samples possess a high photoionization cross section when exposed to blue LEDs, which are commonly used as the light source in OSL readers. Different TL glow peaks with varying shapes of the glow curve were observed when the dopant, the co-dopant, and the concentration of silver were altered in the samples. The TL kinetic parameters were determined, such as the order value, activation energy, and frequency factor, and the OSL parameters for the compound were also analyzed, including an exponential fit to the curves. Based on these initial results, we conclude that BioGlass has the potential for use in radiation dosimetry.

Investigation of dosimetric properties of CaSO4:Mn phosphor prepared using slow evaporation route.

The objective of this work was to investigate the luminescent properties of CaSO4:Mn synthesized by slow evaporation route. The crystalline structure, morphology, thermal and optical properties of the phosphors were characterized by X-ray diffraction analysis (XRD), Scanning electron microscopy (SEM), photoluminescence (PL) and thermogravimetric analysis (TGA). Moreover, using thermoluminescence (TL) and optically stimulated luminescence (OSL) techniques, the dosimetric properties of the phosphors, such as emission spectra, glow curve reproducibility, dose-response linearity, fading of the luminescent signal, variation of the TL intensity with the heating rate, OSL decay curves, correlation between TL and OSL emissions and minimum detectable dose (MDD) were comprehensively investigated. For dosimetric analyses, the samples were irradiated with doses from 169 mGy to 10 Gy. The emission band fits with the characteristic line of the Mn2+ emission features, ascribed to 6A1→4T1 transition. CaSO4:Mn pellets present a TL glow curve with a single typical peak centered around 494 nm, an OSL decay curve with predominance of a fast decay component, and a MDD on the order of mGy. The luminescent signals showed to be linear and reproducible in the studied dose range. The trapping centers located between 0.83 eV and 1.07 eV were revealed for different heating rates in the TL study. The high TL sensitivity of CaSO4:Mn was proven when comparing with commercially available dosimeters. The luminescent signals exhibit a smaller fading than described in the literature for CaSO4:Mn produced by other methods.

'Bundle busters': who is at risk of exceeding the target payment and can they be optimized?

AIMS: The Bundled Payments for Care Improvement (BPCI) initiative has identified pathways for improving the value of care. However, patient-specific modifiable and non-modifiable risk factors may increase costs beyond the target payment. We sought to identify risk factors for exceeding our institution's target payment, the so-called 'bundle busters'. PATIENTS AND METHODS: Using our data warehouse and Centers for Medicare and Medicaid Services (CMS) data we identified all 412 patients who underwent total joint arthroplasty and qualified for our institution's BPCI model, between July 2015 and May 2017. Episodes where CMS payments exceeded the target payment were considered 'busters' (n = 123). Risk ratios (RRs) were calculated using a modified Poisson regression analysis. RESULTS: An increased risk of exceeding the target payment was significantly associated with increasing age (adjusted RR 1.04, 95% confidence interval (CI) 1.01 to 1.06) and body mass index (adjusted RR 1.03, 95% CI 1.003 to 1.06). Eight comorbid risk factors were also identified (all p < 0.05), only two of which were considered to be potentially modifiable (diabetes with complications and preoperative anaemia). An American Society of Anesthesiologist physical status classification system (ASA) score ≥ 3 (adjusted RR 2.3, 95% CI 1.67 to 3.18) and Charlson Comorbidity Index (CCI) ≥ 3 (adjusted RR 1.94, 95% CI 1.45 to 2.60) were risk factors for bundle busting. CONCLUSION: Non-modifiable preoperative risk factors can increase costs and exceed the target payment. Future bundled payment models should incorporate the stratification of risk. Cite this article: Bone Joint J 2019;101-B(7 Supple C):64-69.

Correction of mildly dysplastic hips with periacetabular osteotomy demonstrates promising outcomes, achievement of correction goals, and excellent five-year survivorship.

AIMS: The aim of this study was to compare patient-reported outcome measures (PROMs), radiological measurements, and total hip arthroplasty (THA)-free survival in patients who underwent periacetabular osteotomy (PAO) for mild, moderate, or severe developmental dysplasia of the hip. PATIENTS AND METHODS: We performed a retrospective study involving 336 patients (420 hips) who underwent PAO by a single surgeon at an academic centre. After exclusions, 124 patients (149 hips) were included. The preoperative lateral centre-edge angle (LCEA) was used to classify the severity of dysplasia: 18° to 25° was considered mild (n = 20), 10° to 17° moderate (n = 66), and < 10° severe (n = 63). There was no difference in patient characteristics between the groups (all, p > 0.05). Pre- and postoperative radiological measurements were made. The National Institute of Health's Patient Reported Outcomes Measurement Information System (PROMIS) outcome measures (physical function computerized adaptive test (PF CAT), Global Physical and Mental Health Scores) were collected. Failure was defined as conversion to THA or PF CAT scores < 40, and was assessed with Kaplan-Meier analysis. The mean follow-up was five years (2 to 10) ending in either failure or the latest contact with the patient. RESULTS: There was no significant difference in PROMs for moderate (p = 0.167) or severe (p = 0.708) groups compared with the mild dysplasia group. The numerical pain scores were between 2 and 3 units in all groups at the final follow-up (all, p > 0.05). There was no significant difference (all, p > 0.05) in the proportion of patients achieving target correction for the LCEA between groups. The mean correction was 12° in the mild, 15° in the moderate (p = 0.135), and 23° in the severe group (p < 0.001). Failure-free survival at five years was 100% for mild, 79% for moderate, and 92% for severely dysplastic hips (p = 0.225). CONCLUSION: Although requiring less correction than hips with moderate or severe dysplasia, we found PAO for mild dysplasia to be associated with promising PROMs, consistent with that of the general United States population, and excellent survivorship at five years. Future studies should compare these results with the outcome after arthroscopy of the hip in patients with mild dysplasia. Cite this article: Bone Joint J 2019;101-B(6 Supple B):16-22.

Ten-year survivorship of primary total hip arthroplasty in patients 30 years of age or younger.

Aims: For this retrospective cohort study, patients aged ≤ 30 years (very young) who underwent total hip arthroplasty (THA) were compared with patients aged ≥ 60 years (elderly) to evaluate the rate of revision arthroplasty, implant survival, the indications for revision, the complications, and the patient-reported outcomes. Patients and Methods: We retrospectively reviewed all patients who underwent primary THA between January 2000 and May 2015 from our institutional database. A total of 145 very young and 1359 elderly patients were reviewed. The mean follow-up was 5.3 years (1 to 18). Logistic generalized estimating equations were used to compare characteristics and the revision rate. Survival was evaluated using Kaplan-Meier curves and hazard rates were created using Cox regression. Results: The overall revision rate was 11% (16/145) in the very young and 3.83% (52/1359) in the elderly groups (odds ratio (OR) 2.58, 95% confidence interval (CI) 1.43 to 4.63). After adjusting for the American Society of Anesthesiologists (ASA) score, gender, and a history of previous surgery in a time-to-event model, the risk of revision remained greater in the very young (adjusted hazard ratio (HR) 2.48, 95% CI 1.34 to 4.58). Survival at ten years was 82% (95% CI, 71 to 89) in the very young and 96% (95% CI, 94 to 97) in the elderly group (p < 0.001). The very young had a higher rate of revision for complications related to metal-on-metal (MoM) bearing surfaces (p < 0.001). At last follow-up, the very young group had higher levels of physical function (p = 0.002), lower levels of mental health (p = 0.001), and similar levels of pain (p = 0.670) compared with their elderly counterparts. Conclusion: The overall revision rate was greater in very young THA patients. This was largely explained by the use of MoM bearings. Young patients with non-MoM bearings had high survivorship with similar complication profiles to patients aged ≥ 60 years. Cite this article: Bone Joint J 2018;100-B:867-74.

Carotid stenting in asymptomatic patients: how to identify patients without symptoms and at high risk for neurologic events.

During the last 20 years, asymptomatic patients with high-grade carotid stenosis have been treated with carotid endarterectomy and more recently with carotid artery stenting in order to prevent stroke. New, best medical treatment including statins, beta-blockers, antiplatelet therapies, and better diabetes and blood pressure control might reduce the incidence of stroke in this patient population making invasive treatment unnecessary. However, patients with asymptomatic carotid stenosis cannot be considered a homogenous population, and therefore, the therapeutic approach should take into consideration a subgroup of patients with greater risk of cerebrovascular event. Unfortunately, these risk factors are not well categorized thus far, although multiple publications have addressed each one of these factors individually. Recognizing these risk factors is essential for optimizing surveillance and therapeutic approach based on individual risk. The purpose of this article is to review such factors, including patient history, presence of embolic signals on Transcranial Doppler ultrasound, and plaque morphology. These factors should identify high risk asymptomatic individuals who could benefit from carotid stenting or carotid endarterectomy.

Potential mechanisms for hypoalgesia induced by anti-nerve growth factor immunoglobulin are identified using autoimmune nerve growth factor deprivation.

Nerve growth factor (NGF) antagonism has long been proposed as a chronic pain treatment. In 2010, the FDA suspended clinical trials using tanezumab, a humanized monoclonal anti-NGF antibody, to treat osteoarthritis due to worsening joint damage in 16 patients. Increased physical activity in the absence of acute pain which normally prevents self-harm was purported as a potential cause. Such an adverse effect is consistent with an extension of tanezumab's primary mechanism of action by decreasing pain sensitivity below baseline levels. In animal inflammatory pain models, NGF antagonism decreases intraepidermal nerve fiber (IENF) density and attenuates increases in expression of nociception-related proteins, such as calcitonin gene-related peptide (CGRP) and substance P (SP). Little is known of the effects of NGF antagonism in noninflamed animals and the hypoalgesia that ensues. In the current study, we immunized rats with NGF or cytochrome C (cytC) and examined (1) nocifensive behaviors with thermal latencies, mechanical thresholds, the hot plate test, and the tail flick test, (2) IENF density, and (3) expression of CGRP, SP, voltage-gated sodium channel 1.8 (Nav1.8), and glutaminase in subpopulations of dorsal root ganglion (DRG) neurons separated by size and isolectin B4 (IB4) labeling. Rats with high anti-NGF titers had delayed responses on the hot plate test but no other behavioral abnormalities. Delayed hot plate responses correlated with lower IENF density. CGRP and SP expression was decreased principally in medium (400-800 µm(2)) and small neurons (<400 µm(2)), respectively, regardless of IB4 labeling. Expression of Nav1.8 was only decreased in small and medium IB4 negative neurons. NGF immunization appears to result in a more profound antagonism of NGF than tanezumab therapy, but we hypothesize that decreases in IENF density and nociception-related protein expression are potential mechanisms for tanezumab-induced hypoalgesia.

Postoperative recovery advantages in patients undergoing thyroid and parathyroid surgery under regional anesthesia.

Thyroid or parathyroid surgery may be performed using general anesthesia or regional anesthesia. Ninety-five (95) patients underwent thyroid or parathyroid surgery using general anesthesia (n=64) or bilateral superficial cervical plexus block with sedation (n=31) and completed a postoperative questionnaire regarding the perioperative experience. Patients undergoing parathyroid surgery under regional anesthesia (n=24) were more likely to experience better energy levels (p=0.012) and earlier return to work (p=0.045) postoperatively. Overall, 96% of patients undergoing either type of surgery with either type of anesthetic reported satisfaction with the anesthetic.

Tumor prevention by 9-cis-retinoic acid in the N-nitroso-N-methylurea model of mammary carcinogenesis is potentiated by the pineal hormone melatonin.

Our laboratory has demonstrated that treatment of MCF-7 breast cancer cells with melatonin (Mlt) followed 24h later with physiological concentrations of all-trans retinoic acid (atRA) results in apoptosis. These studies were extended into trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model. Initial studies conducted by feeding the animals 9-cis-retinoic acid (9cRA in the chow) and administering melatonin by subcutaneous injection in the late afternoon demonstrated that the combination of Mlt and 9cRA was able to significantly prevent tumor development, and that the combination was more efficacious that either Mlt or 9cRA alone. In this report, we conducted studies to determine if lower doses of 9cRA could be used in combination with Mlt while still maintaining anti-tumor activity and if the route of administration of 9cRA (bolus (gavage) v.s. chronic (chow) routes) affected its interaction with Mlt. The studies presented here demonstrate that significantly reduced doses of 9cRA can be used in combination with Mlt while maintaining anti-tumor efficacy. Furthermore, our studies demonstrate that 9cRA is equally effective when it is administered chronically (chow) or as a bolus (gavage). These data demonstrate that the combined use of Mlt and 9cRA produces additive or synergistic effects, which are more efficacious than 9cRA alone. This combination of Mlt and 9cRA could be a potentially useful clinical treatment regimen for breast cancer since it allows the use of lower doses of retinoic acid, thus, avoiding the toxic side effects associated with the use of high dose retinoids.

Thoracic epidural anesthesia for coronary bypass via left anterior thoracotomy in the conscious patient.

Cardiac surgery is perceived to be maximally invasive and fraught with complications. Secondary to this, cardiothoracic surgeons have been refining traditional techniques to minimize their invasive nature. Epidural anesthesia has been utilized safely and effectively for numerous surgical procedures to reduce the associated morbidity. In hopes of achieving a similar result, we utilized thoracic epidural anesthesia for a coronary artery bypass via a left anterior thoracotomy, in an awake, spontaneously breathing patient. To the best of our knowledge, this is the first reported case utilizing this approach. Herein we report the results and technique utilized.

Chemoprevention of NMU-induced rat mammary carcinoma with the combination of melatonin and 9-cis-retinoic acid.

In experimental trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model, a significant decrease in tumor incidence (to 5%) was observed in rats treated with melatonin and 9-cis-retinoic acid (9 cRA) compared to controls (55%). Although 9cRA alone decreased tumor incidence to 26%, this response did not reach statistical significance. Tumor incidence was significantly inhibited to 20% in the animals that received melatonin and 9cRA on alternating days. Latency to tumor onset was prolonged in animals receiving either of the combination treatments compared with controls, and tumor multiplicity was also significantly decreased.

Gonadal cysts in spotted gar (Lepisosteus oculatus) from Bayou Trepagnier, Louisiana, USA.

Gonadal cysts of spotted gar (Lepisosteus oculatus), an air-breathing teleost commonly found in Louisiana waters, are described. Fish were collected from two sites: Bayou Trepagnier, a petroleum-contaminated site (30 males and 42 females), and Bayou Traverse, a control site (17 males and 15 females). After fish were evaluated for gross abnormalities, they were necropsied and the gonads, gonadal ducts, and gonadal cysts were evaluated histologically. Multilocular fluid-filled cysts were noted in the testes, or spermatic ducts of four spotted gars from the Bayou Trepagnier. Unilateral ovarian cystadenomas were present in one female from Bayou Trepagnier. No cysts were observed in the gonads of spotted gar from the control site.

Effects of cadmium cell viability, trophoblastic development, and expression of low density lipoprotein receptor transcripts in cultured human placental cells.

Previously, we have demonstrated that cadmium inhibits progesterone release in cultured human trophoblast cells. In the present study, we investigated potential mechanism(s) by which cadmium may elicit this effect. Cytotrophoblasts were obtained via enzymatic dispersion, purified by density gradient centrifugation, and cultured with increasing concentrations of cadmium. Cadmium-induced suppression of progesterone release seemed to be independent of cell death, as no significant decline in viability was observed with cadmium treatment. Further, immunocytochemical localization of cellular boundaries and nuclei indicated approximately 94% syncytial maturity was attained by both untreated and cadmium-treated cells, demonstrating that cadmium did not inhibit syncytial development. However, the abundance of LDL receptor (LDL-R) mRNA transcripts, as determined by competitive RT-PCR, was reduced (P < 0.05) by cadmium exposure in an apparent dose-dependent manner. Thus, the LDL-R, by which cholesterol substrate is supplied to the syncytiotrophoblast, is one site at which cadmium may interfere with placental progesterone production.

Transformation of medical students' education: work in progress and continuing challenges.

In his book Time to Heal: American Medical Education from the Turn of the Century to the Era of Managed Care, Ludmerer expresses concern about the erosion of the environment in which medical students and residents learn the clinical skills, attitudes, and behaviors that they will need to practice high-quality medicine. Importantly, while he attributes the erosion of the clinical environment largely to the impact of managed care, he also places some responsibility within academic medicine itself, primarily the redirection of the clinical faculty's efforts away from traditional academic pursuits to the generation of clinical revenues. The Association of American Medical Colleges has information about the kinds of changes already occurring. In the preclinical curriculum, schools have introduced a wide range of new courses and topics, and there is more attention on professionalism and values. Schools are making fundamental changes in the design and conduct of the curriculum, primarily by adopting more integrated (non-departmental) approaches to course design and management. The clinical curriculum is changing primarily through the greatly expanded use of ambulatory care sites, and medical schools are developing new approaches to managing dispersed and varied instruction. Also, faculty are paying more attention to the role of residents as teachers and role models. These changes speak well for medical education. Nonetheless, substantial and sustained work remains to be done despite the present uncertainty about the future of academic medical centers. This work is essential--a challenge that the leaders of academic medicine must not fail.

Blue light-directed destabilization of the pea Lhcb1*4 transcript depends on sequences within the 5' untranslated region.

Pea seedlings grown in continuous red light accumulate significant levels of Lhcb1 RNA. When treated with a single pulse of blue light with a total fluence >10(4) micromol m(-2), the rate of Lhcb1 transcription is increased, whereas the level of Lhcb1 RNA is unchanged from that in control seedlings. This RNA destabilization response occurs in developing leaves but not in the apical bud. The data presented here indicate that the same response occurs in the cotyledons of etiolated Arabidopsis seedlings. The blue light-induced destabilization response persists in long hypocotyl hy4 and phytochrome phyA, phyB, and hy1 mutants as well as in far-red light-grown seedlings, indicating that neither CRY1 (encoded by the hy4 locus) nor phytochrome is the sole photoreceptor. Studies with transgenic plants indicate that the destabilization element in the pea Lhcb1*4 transcript resides completely in the 5' untranslated region.