Correction to: Uncemented Thompson's hemiarthroplasty: safe, palliative and cost-effective surgery in the infirm patient-a consecutive series of 1445 cases.

The original version of this article unfortunately contained a mistake. David Morley was not listed among the authors.

Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial.

BACKGROUND: Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation). Preclinically, trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity. PATIENTS AND METHODS: This was a phase Ib (open-label, dose-finding) and phase II (randomized, double-blind placebo-controlled) study of the safety, efficacy and PK of trilaciclib in combination with etoposide/carboplatin (E/P) therapy for treatment-naive extensive-stage small-cell lung cancer patients. Patients received trilaciclib or placebo before E/P on days 1-3 of each cycle. Select end points were prespecified to assess the effect of trilaciclib on myelosuppression and antitumor efficacy. RESULTS: A total of 122 patients were enrolled, with 19 patients in part 1 and 75 patients in part 2 receiving study drug. Improvements were seen with trilaciclib in neutrophil, RBC (red blood cell) and lymphocyte measures. Safety on trilaciclib+E/P was improved with fewer ≥G3 adverse events (AEs) in trilaciclib (50%) versus placebo (83.8%), primarily due to less hematological toxicity. No trilaciclib-related ≥G3 AEs occurred. Antitumor efficacy assessment for trilaciclib versus placebo, respectively, showed: ORR (66.7% versus 56.8%, P = 0.3831); median PFS [6.2 versus 5.0 m; hazard ratio (HR) 0.71; P = 0.1695]; and OS (10.9 versus 10.6 m; HR 0.87; P = 0.6107). CONCLUSION: Trilaciclib demonstrated an improvement in the patient's tolerability of chemotherapy as shown by myelopreservation across multiple hematopoietic lineages resulting in fewer supportive care interventions and dose reductions, improved safety profile, and no detriment to antitumor efficacy. These data demonstrate strong proof-of-concept for trilaciclib's myelopreservation benefits. CLINICAL TRAIL NUMBER: NCT02499770.

Uncemented Thompson's hemiarthroplasty: safe, palliative and cost-effective surgery in the infirm patient-a consecutive series of 1445 cases.

BACKGROUND: Guidelines on the management of displaced intracapsular fractures recommend using an Orthopaedic Data Evaluation Panel-rated cemented implant. Prior to the National Institute for Health and Care Excellence guidelines, uncemented implants were commonly used in the UK. METHODS: We retrospectively examined the outcomes of patients with uncemented Thompson's hemiarthroplasties at our unit, between April 2005 and December 2010. Patients who underwent revision surgery before December 2011 were identified. Implant survival calculation utilised the primary outcome of revision to total hip arthroplasty, revision hemiarthroplasty or excision arthroplasty. Patients who died post-operatively were identified and censored. RESULTS: A total of 1445 patients received uncemented Thompson's implant. Patient mean age was 82 years with 76% female. Forty-six (3.2%) patients required revision with 15% performed within 30 days of surgery and 62% within 1 year. Reasons for revision were infection (0.83%), acetabular erosion (0.83%) and loosening (0.62%). Twenty-seven patients (59% of total revisions) underwent revision to THA, 14 (30%) to excision arthroplasty and 5 (11%) to revision hemiarthroplasty. Cumulative survival rate was 98% at 1 year and 95% at 5 years. Thirty-day mortality was 7.1%. One-year mortality was 28.1%. CONCLUSION: Current guidelines strongly favour cemented hemiarthroplasty. Recognition that fractured hip patients are a non-homogeneous group is important. In patients with limited life expectancy, an uncemented Thompson is a quick, simple, palliative solution to early mobilisation. Correct surgical technique avoids using cement in this cohort, which is most vulnerable to bone cement implantation syndrome. Cost-effective resource utilisation with an increasingly elderly population remains a surgical responsibility.

Cause of death and factors associated with early in-hospital mortality after hip fracture.

The aims of this study were to identify the early in-hospital mortality rate after hip fracture, identify factors associated with this mortality, and identify the cause of death in these patients. A retrospective cohort study was performed on 4426 patients admitted to our institution between the 1 January 2006 and 31 December 2013 with a hip fracture (1128 male (26%), mean age 82.0 years (60 to 105)). Admissions increased annually, but despite this 30-day mortality decreased from 12.1% to 6.5%; 77% of these were in-hospital deaths. Male gender (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.3 to 3.0), increasing age (age ≥ 91; OR 4.1, 95% CI 1.4 to 12.2) and comorbidity (American Society of Anesthesiologists grades 3 to 5; OR 4.2, 95% CI 2.0 to 8.7) were independently and significantly associated with increased odds of in-hospital mortality. From 220 post-mortem reports, the most common causes of death were respiratory infections (35%), ischaemic heart disease (21%), and cardiac failure (13%). A sub-group of hip fracture patients at highest risk of early death can be identified with these risk factors, and the knowledge of the causes of death can be used to inform service improvements and the development of a more didactic care pathway, so that multidisciplinary intervention can be focused for this sub-group in order to improve their outcome.

Low loss broadband transmission in hypocycloid-core Kagome hollow-core photonic crystal fiber.

We report on the fabrication of a seven-cell-core and three-ring-cladding large-pitch Kagome-lattice hollow-core photonic crystal fiber (HC-PCF) with a hypocycloid-shaped core structure. We demonstrate experimentally and theoretically that the design of this core shape enhances the coupling inhibition between the core and cladding modes and offers optical attenuation with a baseline of ∼180 dB/km over a transmission bandwidth larger than 200 THz. This loss figure rivals the state-of-the-art photonic bandgap HC-PCF while offering an approximately three times larger bandwidth and larger mode areas. Also, it beats the conventional circular-core-shaped Kagome HC-PCF in terms of the loss. The development of this novel (to our knowledge) HC-PCF has potential for a number of applications in which the combination of a large optical bandwidth and a low loss is a prerequisite.

Stress induced birefringence in hybrid TIR/PBG guiding solid photonic crystal fibers.

We report on two types of polarization maintaining solid photonic crystal fibers that guide light by a combination of a photonic bandgap and total internal reflection. Group and phase birefringence are studied experimentally and numerically for stress-applying parts made from B-doped and F-doped silica. The stress field originating from Ge-doped cladding rods is shown to interfere with the stress field from the B-doped and F-doped rods. Since the differential expansion coefficients of B-doped and F-doped silica have opposite signs this interference is either destructive or constructive. Consequently, we found that the fiber with F-doped stress applying parts has the highest modal phase birefringence, and polarization cross talk is characterized by an h-parameter below 310(-5) m(-1).

Closed double-lumen suction irrigation in the management of chronic diaphyseal osteomyelitis: long-term follow-up.

Between November 1994 and June 1999, 35 patients referred to our Problem Fracture Service with chronic diaphyseal osteomyelitis were treated using a closed double-lumen suction irrigation system after reaming and arthroscopic debridement of the intramedullary canal. This is a modified system based on that of Lautenbach. Between June and July 2007 the patients were reviewed by postal questionnaire and telephone and from the case notes. At a mean follow-up of 101 months (2 to 150), 26 had no evidence of recurrence and four had died from unrelated causes with no evidence of recurrent infection. One had been lost to follow-up at two months and was therefore excluded. Four had persisting problems with sinus discharge and one had his limb amputated for recurrent metaplastic change. Our results represent a clearance of infection of 85.3% (29 of 34), with recurrence in 11.8% (4 of 34). They are comparable to the results of the Papineau and Belfast techniques, but with considerably less surgical insult to the patient.

7-cell core hollow-core photonic crystal fibers with low loss in the spectral region around 2 microm.

Several 7 cell core hollow-core photonic crystal fibers with bandgaps in the spectral range of 1.4 microm to 2.3 microm have been fabricated. The transmission loss follows the approximately lambda(-3) dependency previously reported, with a minimum measured loss of 9.5 dB/km at 1.99 microm. One fiber with a transmission loss of 26 dB/km at 2.3 microm is reported, which is significantly lower than the transmission loss of solid silica fibers at this wavelength.

Square-lattice large-pitch hollow-core photonic crystal fiber.

We report on the design, fabrication and characterization of silica square-lattice hollow core photonic crystal fibers optimized for low loss guidance over an extended frequency range in the mid-IR region of the optical spectrum. The fiber's linear optical properties include an ultra-low group velocity dispersion and a polarization cross-coupling as low as -13.4 dB over 10 m of fiber.

Fourth-order dispersion mediated solitonic radiations in HC-PCF cladding.

We observe experimentally, for the first time to our knowledge, the simultaneous emission of two strong conjugate resonant dispersive waves by optical solitons. The effect is observed in a small waveguiding glass feature within the cladding of a Kagome hollow-core photonic crystal fiber. We demonstrate theoretically that the phenomenon is attributed to the unusually high fourth-order dispersion coefficient of the waveguiding feature.

Nonlinear interaction between two different photonic bandgaps of a hybrid photonic crystal fiber.

Nonlinear interaction between spectral components in two different photonic bandgaps is experimentally demonstrated by launching femtosecond pulses near a zero-dispersion wavelength of a hybrid photonic crystal fiber, which guides by a combination of total internal reflection and bandgap effects. It is demonstrated that the initial pulse becomes spectrally broadened, and narrowband resonant radiation is generated in a different bandgap from the one responsible for guiding at the pump wavelength. The spectral intensity of the resonant radiation peaks at 2.7 dB below that of the broadened pulse in the pump-guiding bandgap.

Dispersive pulse compression in hollow-core photonic bandgap fibers.

Compression of linearly chirped picosecond pulses in hollow-core photonic bandgap fibers is investigated numerically. The modal properties of the fibers are modeled using the finite-element technique, whereas nonlinear propagation is described by a generalized nonlinear Schrödinger equation, which accounts both for the composite nature of the nonlinearity and the strong mode profile dispersion. Power limits for compression with more than 90% of the pulse energy in the main peak of the compressed pulse are investigated as a function of fiber design, and the temporal and spectral widths of the input pulse. The validity of approximate scaling rules is investigated, and figures of merit for fiber design are discussed.

Generation and photonic guidance of multi-octave optical-frequency combs.

Ultrabroad coherent comb-like optical spectra spanning several octaves are a chief ingredient in the emerging field of attoscience. We demonstrate generation and guidance of a three-octave spectral comb, spanning wavelengths from 325 to 2300 nanometers, in a hydrogen-filled hollow-core photonic crystal fiber. The waveguidance results not from a photonic band gap but from the inhibited coupling between the core and cladding modes. The spectrum consists of up to 45 high-order Stokes and anti-Stokes lines and is generated by driving the confined gas with a single, moderately powerful (10-kilowatt) infrared laser, producing 12-nanosecond-duration pulses. This represents a reduction by six orders of magnitude in the required laser powers over previous equivalent techniques and opens up a robust and much simplified route to synthesizing attosecond pulses.

Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.

Mitogen-activated protein kinase (MAPK) cascades are key signaling pathways involved in the regulation of normal cell proliferation, survival and differentiation. Aberrant regulation of MAPK cascades contribute to cancer and other human diseases. In particular, the extracellular signal-regulated kinase (ERK) MAPK pathway has been the subject of intense research scrutiny leading to the development of pharmacologic inhibitors for the treatment of cancer. ERK is a downstream component of an evolutionarily conserved signaling module that is activated by the Raf serine/threonine kinases. Raf activates the MAPK/ERK kinase (MEK)1/2 dual-specificity protein kinases, which then activate ERK1/2. The mutational activation of Raf in human cancers supports the important role of this pathway in human oncogenesis. Additionally, the Raf-MEK-ERK pathway is a key downstream effector of the Ras small GTPase, the most frequently mutated oncogene in human cancers. Finally, Ras is a key downstream effector of the epidermal growth factor receptor (EGFR), which is mutationally activated and/or overexpressed in a wide variety of human cancers. ERK activation also promotes upregulated expression of EGFR ligands, promoting an autocrine growth loop critical for tumor growth. Thus, the EGFR-Ras-Raf-MEK-ERK signaling network has been the subject of intense research and pharmaceutical scrutiny to identify novel target-based approaches for cancer treatment. In this review, we summarize the current status of the different approaches and targets that are under evaluation and development for the therapeutic intervention of this key signaling pathway in human disease.

Identification of Bloch-modes in hollow-core photonic crystal fiber cladding.

We report on the experimental visualization of the cladding Bloch-modes of a hollow-core photonic crystal fiber. Both spectral and spatial field nformation is extracted using the approach, which is based on measurement of the near-field and Fresnel-zone that results after propagation over a short length of fiber. A detailed study of the modes near the edges of the band gap shows that it is formed by the influence of three types of resonator: the glass interstitial apex, the silica strut which joins the neighboring apexes, and the air hole. The cladding electromagnetic field which survives the propagation is found to be spatially coherent and to contain contributions from just a few types of cladding mode.

Design of low-loss and highly birefringent hollow-core photonic crystal fiber.

A practical hollow-core photonic crystal fiber design suitable for attaining low-loss propagation is analyzed. The geometry involves a number of localized elliptical features positioned on the glass ring that surrounds the air core and separates the core and cladding regions. The size of each feature is tuned so that the composite core-surround geometry is antiresonant within the cladding band gap, thus minimizing the guided mode field intensity both within the fiber material and at material/air interfaces. A birefringent design, which involves a 2-fold symmetric arrangement of the features on the core-surround ring, gives rise to wavelength ranges where the effective index difference between the polarization modes is larger than 10(-4). At such high birefringence levels, one of the polarization modes retains favorable field exclusion characteristics, thus enabling low-loss propagation of this polarization channel.

Selective mode excitation in hollow-core photonic crystal fiber.

Modes are selectively excited by launching light through the cladding from the side into a hollow-core photonic crystal fiber. Measuring the total output power at the end of the fiber as a function of the angle of incidence of the exciting laser beam provides a powerful diagnostic for characterizing the cladding bandgap. Furthermore, various types of modes on either side of the bandgap are excited individually, and their near-field images are obtained.

Radiation quantities and units--understanding the sievert.

International recommendations for changes to the SI brochure regarding the definition and use of the quantity dose equivalent are presented. The second part of this note is a simple explanation of the difference between a radiation quantity and its unit.