The 1.06 frequency ratio in the cochlea: evidence and outlook for a natural musical semitone

A frequency ratio of about 1.06 often appears in cochlear mechanics, and the question naturally arises, why? The ratio is close to that of the semitone (1.059) in music, giving reason to think that this aspect of musical perception might have a cochlear basis. Here, data on synchronised spontaneous otoacoustic emissions is presented, and a clustering of ratios between 1.05 and 1.07 is found with a peak at 1.063 +/- 0.005. These findings reinforce what has been found from previous sources, which are reviewed and placed alongside the present work. The review establishes that a peak in the vicinity of 1.06 has often been found in human cochlear data. Several possible cochlear models for explaining the findings are described. Irrespective of which model is selected, the fact remains that the cochlea itself appears to be the origin of a ratio remarkably close to an equal-tempered musical semitone, and this close coincidence leads to the suggestion that the inner ear may play a role in constructing a natural theory of music. The outlook for such an enterprise is surveyed.Andrew Bell received funding from the Institute of Physiology and Pathology of Hearing, Warsaw, under contracts 132/IFPS/2015 and 109/IFPS/2017

Otoacoustic Emissions in Smoking and Nonsmoking Young Adults

ObjectivesThe present study investigates the usefulness of transiently evoked otoacoustic emissions (TEOAEs) and distortion product OAEs (DPOAEs) in detecting small changes in the hearing of young smoking adults.MethodsOtoacoustic emissions were acquired from the ears of 48 young adults (age, 20 to 27 years). The dataset was divided into two groups, smoking (24 persons/48 ears) and nonsmoking (24 persons/48 ears). The level of smoking was relatively small in comparison to previous studies, an average of 3.8 years and 8.7 cigarettes per day. In each ear three OAE measurements were made: TEOAEs, DPOAEs, and spontaneous OAEs (SOAEs). Pure tone audiometry and tympanometry were also conducted. Audiometric thresholds did not differ significantly between the datasets. Half-octave-band values of OAE signal to noise ratios and response levels were used to assess statistical differences.ResultsAveraged data initially revealed that differences between the two study groups occurred only for TEOAEs at 1 kHz. However when the datasets were divided into ears with and without SOAEs more differences became apparent, both for TEOAEs and DPOAEs. In ears that exhibited SOAEs, both smokers and nonsmokers, there were no statistically significant differences between evoked OAEs; however in all ears without SOAEs, evoked OAEs were higher in the ears of nonsmokers, by as much as 5 dB. These differences were most prominent in the 1-2 kHz range.ConclusionA general decrease in OAE levels was found in the group of smokers. However, in ears which exhibited SOAEs, there was no difference between the evoked OAEs of smokers and nonsmokers. We conclude that smoking had not yet measurably affected the ears of those with acute hearing (i.e., those who exhibit SOAEs). However, in ears without SOAEs, smokers exhibited smaller evoked OAE amplitudes than nonsmokers, even though their audiometric thresholds were within the norm

Biosimilar G-CSF versus filgrastim and lenograstim in healthy unrelated volunteer hematopoietic stem cell donors

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 μg/kg for lenograstim, 9.8 μg/kg for biosimilar filgrastim, and 9.3 μg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 10⁶, 7.6 × 10⁶, and 7.3 × 10⁶, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF

Musical Ratios in Sounds from the Human Cochlea

The physiological roots of music perception are a matter of long-lasting debate. Recently light on this problem has been shed by the study of otoacoustic emissions (OAEs), which are weak sounds generated by the inner ear following acoustic stimulation and, sometimes, even spontaneously. In the present study, a high-resolution time–frequency method called matching pursuit was applied to the OAEs recorded from the ears of 45 normal volunteers so that the component frequencies, amplitudes, latencies, and time-spans could be accurately determined. The method allowed us to find that, for each ear, the OAEs consisted of characteristic frequency patterns that we call resonant modes. Here we demonstrate that, on average, the frequency ratios of the resonant modes from all the cochleas studied possessed small integer ratios. The ratios are the same as those found by Pythagoras as being most musically pleasant and which form the basis of the Just tuning system. The statistical significance of the results was verified against a random distribution of ratios. As an explanatory model, there are attractive features in a recent theory that represents the cochlea as a surface acoustic wave resonator; in this situation the spacing between the rows of hearing receptors can create resonant cavities of defined lengths. By adjusting the geometry and the lengths of the resonant cavities, it is possible to generate the preferred frequency ratios we have found here. We conclude that musical perception might be related to specific geometrical and physiological properties of the cochlea

Mobilizacja macierzystych komórek krwiotwórczych u chorych z niedawnorozpoznaną cukrzycą typu 1 przed przeszczepieniem autologicznych komórek krwiotwórczych

BackgroundThe immunoablation with autologous hematopoietic stem cell transplantation is a new experimental treatment of early diabetes type 1. The treatment is based on destruction of immune system with cytotoxic drugs which leads to halt of immune reaction directed against beta cells of pancreas. During that treatment young patients with diabetes type 1 who are otherwise healthy undergo mobilization with cyclophosphamide (CY) and G-CSF. They are naïve to cytotoxic drugs and mobilization is their first contact with chemotherapy. We analyzed the efficiency of mobilization with cyclophosphamide and G-CSF in this population.MethodsWe analyzed the medical records of 25 patients with diabetes who underwent mobilization with cyclophosphamide and G-CSF.ResultsThe median white blood cell count on the first day of apheresis was 14.6×103/μL (range 1.5–33.3) in CY+G-CSF mobilized patients. Median absolute CD 34+ cell count in peripheral blood on the first apheresis day was 0.095 127×103/μL (range 0.026–0.477). The median total number of collected CD34+ cells during one or two (if needed) aphereses was 466×106 (range 204–816) or 7.24×106 CD34+ cells per kg of patient body weight (range 3.03–13.1). There were no poor mobilizers who were unable to collect sufficient cell numbers.ConclusionThe mobilization of hematopoietic stem cells with CY+G-CSF in patients with early diabetes type 1 is efficient and the underlying diabetes does not impair the efficiency of hematopoietic stem cell collection

Identification of cell cycle–arrested quiescent osteoclast precursors in vivo

Osteoclasts are multinucleated cells that resorb bone. Although osteoclasts originate from the monocyte/macrophage lineage, osteoclast precursors are not well characterized in vivo. The relationship between proliferation and differentiation of osteoclast precursors is examined in this study using murine macrophage cultures treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB (RANK) ligand (RANKL). Cell cycle–arrested quiescent osteoclast precursors (QuOPs) were identified as the committed osteoclast precursors in vitro. In vivo experiments show that QuOPs survive for several weeks and differentiate into osteoclasts in response to M-CSF and RANKL. Administration of 5-fluorouracil to mice induces myelosuppression, but QuOPs survive and differentiate into osteoclasts in response to an active vitamin D3 analogue given to those mice. Mononuclear cells expressing c-Fms and RANK but not Ki67 are detected along bone surfaces in the vicinity of osteoblasts in RANKL-deficient mice. These results suggest that QuOPs preexist at the site of osteoclastogenesis and that osteoblasts are important for maintenance of QuOPs

Melphalan 140mg/m2 or 200mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

Melphalan at a dose of 200mg/m2 is standard conditioning prior to autologous haematopoietic stem cell transplantation for multiple myeloma, but a dose of 140mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine if melphalan 200 and melphalan 140 are equally effective and tolerable in clinically relevant patient subgroups we analysed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, haematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 (n=245) and melphalan 200 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 versus melphalan 140: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favoured melphalan 140 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 and melphalan 140 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favour melphalan 200 or melphalan 140 for key transplant outcomes (NCT01362972)