Broadband design of silica-PLC mode-dependent-loss equalizer for 2LP-mode transmission systems.

A new configuration of mode-dependent-loss (MDL) equalizer for two linearly-polarized mode transmission systems using the silica planar lightwave circuit platform is proposed. This device acts as an LP01-mode attenuator (precisely, LP01/LP21 mode converter) to adjust the MDL keeping a high transmission of the LP11 modes. Almost all components constructing the device are based on the adiabatic mode conversion, which brings broadband operation. Especially, a newly proposed E12/E22 mode converter plays a key role in broadband MDL equalization. It is numerically revealed that the flattened spectra with designated transmission can be obtained for the wavelength from 1200 nm to 1650 nm.

Design of silica-PLC LP11 mode rotator based on adiabatic mode conversion.

A silica-based LP11 mode rotator, which is one of the basic and indispensable optical components for space division multiplexing, with multiple tapered trenches is proposed. Compared with the conventional interference-based LP11 mode rotator with a simple L-shape waveguide, the proposed LP11 mode rotator has many advantages in a mode conversion efficiency, an insertion loss, and a fabrication tolerance because the operation principle is based on the adiabatic mode conversion. By using an approach of the shortcut to adiabaticity, the proposed device is effectively miniaturized rather than the standard tapered structures. Among the LP11 mode rotators in the silica-based mode multi/demultiplexers, the proposed type will be a considerably promising candidate.

Neonatal Outcomes of Infants Born to Women on Hemodialysis: A Single-Center, Case-Control Study.

OBJECTIVE: The study aimed to investigate the neonatal outcomes of infants born to mothers on hemodialysis. STUDY DESIGN: This retrospective, case-control, and observational study included 17 infants born to 16 mothers on dialysis in 2003 to 2016. We compared their clinical characteristics to those of 51 gestational age- and sex-matched control infants. Statistical comparisons were made between the two groups by using the Wilcoxon-Mann-Whitney test for continuous variables and the Chi-square test or Fisher's exact test for categorical variables. RESULTS: Of the 16 pregnancies of mothers on dialysis, 15 (94%) deliveries were premature (<37 weeks), and 16/17 (94%) infants survived to discharge. The incidences of neonatal complications, such as intraventricular hemorrhage, bronchopulmonary dysplasia, patent ductus arteriosus, and periventricular leukomalacia, were not significantly different between the groups. However, 5/17 (29%) of the infants had congenital anomalies. CONCLUSION: Although infants born to mothers on dialysis have a high risk of prematurity, they do not have any additional risk of neonatal complications, except for congenital anomalies. The potential risk of congenital anomalies should be investigated further. KEY POINTS: · Preterm birth rate among mothers on hemodialysis was 94%.. · Complications in these infants were similar to controls.. · Twenty-nine percent of infants had congenital anomalies..

Comparison of the Clinical Characteristics of Infants with Punctate White Matter Lesions and/or Cystic Lesions.

BACKGROUND: We aimed to investigate the differences in the clinical characteristics of preterm infants with punctate white matter lesions (PWMLs) and those with cystic periventricular leukomalacia (cPVL) using term-equivalent age magnetic resonance imaging. METHODS: We conducted a retrospective case-control study to explore the clinical characteristics of infants (< 35 weeks gestation, born between 2007 and 2017 in a single Level III perinatal center) with PWML, cPVL or with PWML plus cPVL and compared them with those of gestational-age-matched controls. RESULTS: Among 602 infants, 29, 5, and 4 were assigned to the PWML group, cPVL group, and PWML plus cPVL group (PWML-cPVL group), respectively. Compared to the control group (n = 87), the PWML group had higher birth weights (p = 0.04), rates of histological chorioamnionitis (p = 0.04), vaginal delivery (p = 0.008), and early heart contraction failure (within 72 hours after birth) (p = 0.003). The cPVL group had lower umbilical blood gas base excess (p = 0.01), higher rate of late-onset circulatory collapse (p = 0.008), and higher hydrocortisone requirements (p = 0.03) than the control group (n = 15). The PWML-cPVL group had a higher rate of intraventricular hemorrhage (p = 0.03) than the control group (n = 12). In the multivariate logistic regression analysis, vaginal delivery (odds ratio [OR] = 3.5; 95% confidence interval [CI] = 1.37-9.40; p = 0.009), higher birth weight (per 1 g) (OR = 1.001; 95% CI = 1.0001-1.002; p = 0.03), and early heart contraction failure (OR = 5.4; 95% CI = 1.84-16.8; p = 0.002), were independent risk factors for PWML. CONCLUSION: Clinical characteristics of infants with PWML compared with gestational-age-matched controls differed from those with cPVL or PWML plus cPVL, as PWML were not related to severe disruption of hemodynamics.

BDNF/TRKB axis provokes EMT progression to induce cell aggressiveness via crosstalk with cancer-associated fibroblasts in human parotid gland cancer.

Parotid gland cancer (PGC) is a rare malignancy and its molecular characteristics remain poorly understood, which has precluded the development of effective drug therapies. Given the poor prognosis of many human cancers in which tropomyosin receptor kinase B (TRKB) is highly expressed, we investigated the involvement of brain-derived neurotrophic factor (BDNF)/TRKB pathway in PGC cells using clinical specimens and observed upregulation of TRKB and BDNF. In primary culture systems of patient-derived PGC cells and cancer-associated fibroblasts (CAFs), PGC cells co-cultured with CAFs exhibited significant upregulation of BDNF and epithelial-mesenchymal transition (EMT). Similar results were observed in PGC cells treated with conditioned medium from co-cultures of PGC cells with CAFs. Administration of TRK inhibitors suppressed BDNF-induced cell migration in PGC cells. Immunohistochemical and clinicopathological analyses of tumors from patients with PGC revealed that BDNF and TRKB were highly expressed in both tumor cells and stromal cells such as CAFs, and TRKB expression levels in PGC cells were significantly correlated with aggressive features, including vascular invasion, nodal metastasis, and poor prognosis. Collectively, these data suggest that the BDNF/TRKB pathway regulates PGC cell aggressiveness via crosstalk with CAFs and is a potential therapeutic target for PGC harboring invasive and metastatic features.

Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan.

BACKGROUND: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. METHODS: A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. RESULTS: Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. CONCLUSIONS: Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

Video-based neonatal state assessment method for timing of procedures.

BACKGROUND: Procedures should be performed when an infant is most receptive to disruptions in order to reduce the stress on the infant. However, frequent direct observations place a heavy burden on medical staff. There is therefore a need for a method for quantitatively and automatically evaluating the neonatal state. METHODS: Ten infants in our hospital were enrolled in this study. The states of the infants were assessed by medical staff using the Brazelton Neonatal Behavioral Assessment Scale and were recorded on video at the same time. The recorded states were reclassified as activity levels, a new state classification method that includes middle activity, which is the appropriate time for a procedure. Using image analysis, motions of the infant were quantified as two indices: activity and pause time. Activity and pause time were compared for each activity level. The cutoff values of the indices were calculated, and the sensitivity and specificity of the middle activity were calculated. RESULTS: There was a significant difference between all groups of activity level (P < 0.01). The maximum sensitivity and specificity of middle activity were 71.7% and 51.2%, respectively. CONCLUSIONS: The neonatal state of infants can be quantitatively and automatically evaluated using video cameras, and the activity level can be used to determine an appropriate time for procedures in infants. This will reduce the burden on medical staff and lead to less stressful procedures for infants.

Reduction of differential modal gain in a two-mode amplifier using a void-inscribed EDF.

We propose a technique for reducing the differential modal gain (DMG) that occurs in a two-mode erbium-doped fiber (2M-EDF) by inscribing voids in the core center of a 2M-EDF with a femtosecond laser. We show that an empty void inscribed at the core center can attenuate the linearly polarized (LP01) mode selectively while suppressing excess loss for the LP11 mode. We also reveal that DMG can be controlled by means of void diameter. The longitudinal position dependence of the void in a 2M-EDF was also investigated considering its influence on gain and noise figure (NF) characteristics. Finally, we realize a sufficiently low DMG of less than 0.5 dB in the full C-band as well as a sufficient gain and NF by using the proposed technique.

Thyroid function in asphyxiated newborns who received hypothermia therapy.

BACKGROUND: Thyroid function in asphyxiated newborns who received hypothermia therapy and its relation to neurological outcome are not well described. METHODS: We performed a prospective study to measure thyroid function in 12 asphyxiated newborns who received hypothermia therapy. We measured serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) on admission, at 24, 72, and 96 h after birth, and at discharge (range, 17-54 days). The 12 newborns were divided into two groups based on the presence of brain injury on head magnetic resonance imaging (six in the abnormal imaging group and six in the normal imaging group), and thyroid function was compared between the two groups. RESULTS: Serum TSH was within the normal range in the 12 newborns. Serum FT3 and FT4 remained low at 24, 72, and 96 h after birth, and returned to normal range at discharge in the 12 newborns. There was no significant difference in serum TSH between the two groups, but serum FT3 at 96 h after birth, and serum FT4 at 72 and 96 h after birth, were significantly lower in the abnormal imaging group than in the normal imaging group (P = 0.02; P = 0.03; and P = 0.01, respectively). CONCLUSIONS: Asphyxiated newborns have transient low thyroid hormone levels at 24-96 h after birth. Serum FT3 and FT4 between 72 and 96 h after birth may predict brain injury in asphyxiated newborns.

Status of and problems concerning neonatal resuscitation in Japan in 2015.

BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR) published Consensus 2015 in October 2015. Thereafter, the Japanese version of neonatal cardiopulmonary resuscitation programs was revised. Prior to the revision, we re-conducted questionnaire surveys in three types of medical facilities in January 2015. METHODS: Targeted groups included (i) 277 training hospitals authorized by the Japanese Society of Perinatal/Neonatal Medicine for training of physicians specialized in perinatal care (neonatology) in January 2015 (training hospitals; response rate, 70.8%); (ii) 459 obstetric hospitals/clinics (response rate, 63.6%); and (iii) 453 midwife clinics (response rate, 60.9%). The survey included systems of neonatal resuscitation, medical equipment and practices, and education systems. The results were compared with that of similar surveys conducted in 2005, 2010 and 2013. RESULTS: Almost all results were generally improved compared with past surveys. In training hospitals, however, the use of oxygen blenders or manometers was not widespread. Only 35% of institutions used continuous positive airway pressure systems frequently, and expert neonatal resuscitation doctors attended all deliveries in only 6% of training centers. In addition, only 71% of training hospitals had brain therapeutic hypothermia facilities. Not all obstetric hospitals/clinics prepared pulse oximeters, and only a few used manometers frequently. Some midwife clinics did not keep warming equipment, and few midwife clinics were equipped with pulse oximeters. In addition, some midwife clinics did not prepare ventilation bags (masks). CONCLUSIONS: The equipment in Japanese delivery rooms is variable. Further efforts need to be made in the distribution of neonatal resuscitation devices and the dissemination of techniques.

Criteria for radiologic diagnosis of hypochondroplasia in neonates.

BACKGROUND: A radiologic diagnosis of hypochondroplasia is hampered by the absence of age-dependent radiologic criteria, particularly in the neonatal period. OBJECTIVE: To establish radiologic criteria and scoring system for identifying neonates with fibroblast growth factor receptor 3 (FGFR3)-associated hypochondroplasia. MATERIALS AND METHODS: This retrospective study included 7 hypochondroplastic neonates and 30 controls. All subjects underwent radiologic examination within 28 days after birth. We evaluated parameters reflecting the presence of (1) short ilia, (2) squared ilia, (3) short greater sciatic notch, (4) horizontal acetabula, (5) short femora, (6) broad femora, (7) metaphyseal flaring, (8) lumbosacral interpedicular distance narrowing and (9) ovoid radiolucency of the proximal femora. RESULTS: Only parameters 1, 3, 4, 5 and 6 were statistically different between the two groups. Parameters 3, 5 and 6 did not overlap between the groups, while parameters 1 and 4 did. Based on these results, we propose a scoring system for hypochondroplasia. Two major criteria (parameters 3 and 6) were assigned scores of 2, whereas 4 minor criteria (parameters 1, 4, 5 and 9) were assigned scores of 1. All neonates with hypochondroplasia in our material scored ≥6. CONCLUSION: Our set of diagnostic radiologic criteria might be useful for early identification of hypochondroplastic neonates.

Training of neonatal cardiopulmonary resuscitation instructors.

BACKGROUND: The Consensus on Science and Treatment Recommendations 2010 supported simulation-based training for education in resuscitation. This approach has been introduced into neonatal cardiopulmonary resuscitation (NCPR) courses in Japan, but no method for teaching instructors has been established. We developed a course for training instructors of NCPR, with inclusion of an instruction practice program. The goal of the study was to evaluate the performance of instructors who completed the course. METHODS: Based on problems in the conventional instructor training course (old course 1), we developed and implemented a new course. Persons who had completed an NCPR course took the new course after developing two resuscitation scenarios. The new course included lectures and instruction practice, in which participants provided instruction using these scenarios. Instruction by participants was evaluated, and knowledge, opinions and satisfaction were examined by questionnaire after the course. Activity of the participants as instructors for 6 months after certification was also evaluated. The performance of trained instructors was compared between the old and new courses. RESULTS: Of 143 participants in the new course, > 90% had confidence to teach NCPR, while only 50-60% of the 89 participants in the old course indicated that they could instruct on resuscitation procedures and practice (P < 0.001). All participants in the new course recognized the value of scenario practice and all were glad they had taken the course. For 6 months after certification, significantly more participants who had done the new course worked as instructors compared with those who had done the old course (60% vs 34%, P < 0.001). CONCLUSION: This is the first trial of a resuscitation training course using scenarios that participants developed themselves. A new course including instruction practice for training NCPR instructors was effective for improving instructor performance.

Survey of delivery room resuscitation practices at tertiary perinatal centers in Japan.

BACKGROUND: The aim of this study was to determine the current neonatal resuscitation practices for term infants in Japan, immediately before the 2010 publication of the international neonatal resuscitation consensus. METHODS: In January 2010, a 26-question survey was mailed to neonatal department directors. RESULTS: A total of 287 neonatal departments were identified. Four surveys were returned as undeliverable. A total of 191 surveys were returned completed, but four departments had no labor and delivery rooms (66.6% response rate, 65.2% survey available response rate). Flow-inflating bags were most commonly used (63.2%), followed by self-inflating bags (35.8%), and T-piece resuscitators (1.0%). Among the participants, 42.1% used oxygen blenders, 56.2% used pure oxygen for initial resuscitation, and 79.5% used a pulse oximeter to change the fraction of inspired oxygen. Among the participants, 45.3% used carbon dioxide detectors to confirm intubation, 42.5% routinely used the detectors, and 55.2% used them when confirming a difficult intubation. In addition, 42.5% of the participants used continuous positive airway pressure to treat breathing problems, most commonly with flow-inflating bags (93.2%). CONCLUSIONS: The equipment and techniques used in Japanese perinatal center delivery room resuscitation practices are highly varied. Further research is required to determine which devices and techniques are appropriate for this important and common intervention.

Experimental and numerical evaluation of inter-core differential mode delay characteristic of weakly-coupled multi-core fiber.

We investigated the inter-core differential mode delay (DMD) characteristic of a weakly-coupled homogeneous multi-core fiber with a view to utilizing inter-core crosstalk compensation with MIMO processing. We confirmed experimentally that the bend induced inter-core DMD is lower than the simulated results, which we expected owing to the twist of the fiber. We also revealed numerically that the refractive index profile variation of each core greatly increases inter-core DMD. Finally, we conducted a 4 × 4 MIMO transmission experiment using a weakly-coupled 4-core fiber and successfully compensated for the inter-core crosstalk.

High-dose toremifene as first-line treatment of metastatic breast cancer resistant to adjuvant aromatase inhibitor: A multicenter phase II study.

There is currently no standardized therapy available for metastatic breast cancer in patients with aromatase inhibitor (AI)-resistant breast cancer. We conducted a prospective study to examine the efficacy and safety of high-dose toremifene (TOR) treatment for the first-line treatment of metastatic breast cancer following AI adjuvant therapy. A multicenter phase II study was designed (Registry no.: UMIN000000489). Inclusion criteria comprised hormone-responsive postmenopausal women who had received adjuvant AI postoperatively for >1 year and had relapsed during the treatment or within 12 months of completion of adjuvant therapy. Treatment comprised oral intake of 120 mg TOR once a day. The primary endpoint was objective response rate (ORR). The secondary endpoints were evaluations of clinical benefit (CB), progression-free survival (PFS) and toxicity. A total of 13 patients were enrolled. ORR was 7.7% (1/13) [95% CI, 0.2-36.0%]. In total, 7 patients (53.8%) had stable disease (SD), 5 of whom were long SD, and 5 patients (38.5%) experienced progressive disease (PD). The CB rate was 46.2% (6/13) [95% CI, 19.2-74.9%]. The median time to PFS was 5.9 months. No serious adverse events were observed. Patients with HER2-positive disease exhibited marginally poorer PFS (p=0.08). Patients with PD had a relatively short duration of AI treatment in contrast to responders, who had a longer period of AI treatment (p=0.02). High-dose TOR as a first-line treatment following AI adjuvant therapy was effective and well tolerated. A longer duration of adjuvant AI therapy and negative HER2 overexpression may, with further studies, be beneficial as positive predictive factors for the effectiveness of TOR treatment.

Interleukin-6 polymorphism and bronchopulmonary dysplasia risk in very low-birthweight infants.

BACKGROUND: The aim of the present study was to evaluate the role of interleukin (IL)-6-634 polymorphism in neonatal disorders such as bronchopulmonary dysplasia (BPD) and periventricular leukomalacia (PVL) in very low-birthweight (VLBW) infants. METHODS: This prospective cohort study included 202 infants (gestational age at birth, 23-34 weeks; birthweight, 500-1499 g). Genotypic analysis (polymerase chain reaction-restriction fragment length polymorphism) was performed with DNA extracted from whole-blood samples. RESULTS: Genotype distribution (66.8% CC, 28.2% CG, 5.0% GG) was similar to that in the adult Japanese population. BPD occurred in 85 infants (42.1%) among 202 VLBW infants. The duration of O(2) therapy in infants with CG/GG genotypes was significantly longer than that in infants with the CC genotype (CG/GG vs CC: 40.3 ± 52.2 days vs 28.4 ± 32.6 days, P < 0.05), but the prevalence of BPD was not associated with the CG/GG genotype (CG/GG, 40.0%; CC, 46.3%, P= 0.24). Infants with CG/GG genotypes were more likely to have received postnatal corticosteroid therapy for BPD than those with the CC genotype (CG/GG vs CC: 20.9% vs 11.1%, P = 0.05). PVL occurred in six infants (3.0%). There was no significant difference in the prevalence of PVL among IL-6-634 polymorphisms (CG/GG, 3.0%; CC, 3.0%, P = 0.65). CONCLUSIONS: IL-6-634 polymorphism is associated with duration of oxygen therapy in VLBW infants. This suggests that the IL-6-634 polymorphism G allele is an aggravating factor of BPD. IL-6-634 polymorphism is not associated with PVL.

Prevalence of laryngopharyngeal reflux symptoms: comparison between health checkup examinees and patients with otitis media.

OBJECTIVE: To investigate the prevalence of laryngopharyngeal reflux (LPR) symptoms in health checkup examinees and in patients with otitis media with effusion (OME) of undetermined etiology and the significance of age, body mass index (BMI), and pepsinogen (PG) concentration in middle ear effusions (MEEs). STUDY DESIGN: Cross-sectional study. SETTING: Health checkup and private clinics. SUBJECTS AND METHODS: A total of 410 subjects who had undergone a health checkup were asked to respond to the reflux symptom index (RSI) to identify the distribution of the RSI score, and the results were compared with 62 patients with OME by BMI and PG concentration in the MEEs. RESULTS: The RSI-positive (score >13) rate was 7.1% in the health checkup examinees. The highest rate was observed in men in their 40s, who had the highest average BMI. None of the men in their 80s were RSI positive. The RSI-positive rate in patients with OME was 21.0%. None of the male patients ≥ 70 years of age were RSI positive, whereas the average PG concentration was significantly higher in this group. CONCLUSION: The prevalence of LPR symptoms evaluated by the RSI was significantly higher in OME patients than in the health checkup examinees; however, a similar pattern in which LPR symptoms were prominent in middle-aged men with a high BMI and much less in elderly men was observed. Middle-aged men with a high BMI might be diagnosed as having LPR disease based on the relevant symptoms. LPR findings would be more sensitive than symptoms in elderly men.

A case report of fatal tumor lysis syndrome after chemotherapy in a pregnant patient with Burkitt's lymphoma.

A 35-year-old Japanese woman in the 24th week of gestation with bilateral breast enlargement was referred to hospital. She was diagnosed with Burkitt's lymphoma and admitted for detailed evaluation and treatment. Early delivery and subsequent chemotherapy was chosen after considering the gestational week, her general condition and the wishes of the patient and her husband. She gave birth to a male infant by cesarean section in the 25(th) week of gestation. It had been planned to begin high-dose chemotherapy, such as CODOX-M/IVAC, on day 7 of the puerperium; however, her general condition worsened and chemotherapy was therefore begun on day 2 after the birth. Eight hours after chemotherapy (cyclophosphamide, vincristine and doxorubicin), she developed cardiac arrest due to tumor lysis syndrome. Despite medical treatment, her bleeding tendency did not improve and she died of respiratory failure with alveolar bleeding five days after chemotherapy.