531 research outputs found
Open Vocabulary Extreme Classification Using Generative Models
The extreme multi-label classification (XMC) task aims at tagging content with a subset of labels from an extremely large label set. The label vocabulary is typically defined in advance by domain experts and assumed to capture all necessary tags. However in real world scenarios this label set, although large, is often incomplete and experts frequently need to refine it. To develop systems that simplify this process, we introduce the task of open vocabulary XMC (OXMC): given a piece of content, predict a set of labels, some of which may be outside of the known tag set. Hence, in addition to not having training data for some labels-as is the case in zero-shot classification-models need to invent some labels on-the-fly. We propose GROOV, a fine-tuned seq2seq model for OXMC that generates the set of labels as a flat sequence and is trained using a novel loss independent of predicted label order. We show the efficacy of the approach, experimenting with popular XMC datasets for which GROOV is able to predict meaningful labels outside the given vocabulary while performing on par with state-of-the-art solutions for known labels
Scaffold-associated procedures are superior to microfracture in managing focal cartilage defects in the knee: a systematic review & meta-analysis
BACKGROUND: Debate continues as to whether surgical treatment with chondral-regeneration devices is superior to microfracture for focal articular cartilage defects in the knee. PURPOSE: To evaluate the superiority of scaffold-associated chondral-regeneration procedures over microfracture by assessing: (1) Patient-reported outcomes; (2) Intervention failure; (3) Histological quality of cartilage repair. STUDY DESIGN: A three-concept keyword search strategy was designed, in accordance with PRISMA guidelines: (i) knee (ii) microfracture (iii) scaffold. Four databases (Ovid Medline, Embase, CINAHL and Scopus) were searched for comparative clinical trials (Level I-III evidence). Critical appraisal used two Cochrane tools: the Risk of Bias tool (RoB2) for randomized control trials and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I). Study heterogeneity permitted qualitative analysis with the exception of three patient-reported scores, for which a meta-analysis was performed. RESULTS: Twenty-one studies were identified (1699 patients, age range 18-66Â years): ten randomized control trials and eleven non-randomized study interventions. Meta-analyses of the International Knee Documentation Committee (IKDC), Knee Injury And Osteoarthritis Outcome Score (KOOS) for pain and activities of daily living, and Lysholm score demonstrated statistically significant improvement in outcomes for scaffold procedures compared to microfracture at two years. No statistical difference was seen at five years. CONCLUSION: Despite the limitations of study heterogeneity, scaffold-associated procedures appear to be superior to MF in terms of patient-reported outcomes at two years though similar at five years. Future evaluation would benefit from studies using validated clinical scoring systems, reporting failure, adverse events and long-term clinical follow up to determine technique safety and superiority
Metallic superhydrophobic surfaces via thermal sensitization
Superhydrophobic surfaces (i.e., surfaces extremely repellent to water) allow water droplets to bead up and easily roll off from the surface. While a few methods have been developed to fabricate metallic superhydrophobic surfaces, these methods typically involve expensive equipment, environmental hazards, or multi-step processes. In this work, we developed a universal, scalable, solvent-free, one-step methodology based on thermal sensitization to create appropriate surface texture and fabricate metallic superhydrophobic surfaces. To demonstrate the feasibility of our methodology and elucidate the underlying mechanism, we fabricated superhydrophobic surfaces using ferritic (430) and austenitic (316) stainless steels (representative alloys) with roll off angles as low as 4° and 7°, respectively. We envision that our approach will enable the fabrication of superhydrophobic metal alloys for a wide range of civilian and military applications
Defining aggressive or early progressing nononcogene-addicted non-small-cell lung cancer: a separate disease entity?
A substantial proportion of patients with nononcogene-addicted non-small-cell lung cancer (NSCLC) has 'aggressive disease', as reflected in short time to progression or lack of disease control with initial platinum-based chemotherapy. Recently, clinical correlates of aggressive disease behavior during first-line therapy have been shown to predict greater benefit from addition of nintedanib to second-line docetaxel in adenocarcinoma NSCLC. Positive predictive effects of aggressive disease have since been reported with other anti-angiogenic agents (ramucirumab and bevacizumab), while such features may negatively impact on outcomes with nivolumab in nonsquamous NSCLC with low PD-L1 expression. Based on a review of the clinical data, we recommend aggressive nonsquamous NSCLC should be defined by progression within <6-9Â months of first-line treatment initiation
Defining Unmet Need Following Lenalidomide Refractoriness: Real-World Evidence of Outcomes in Patients With Multiple Myeloma
Background: The treatment paradigm for multiple myeloma (MM) continues to evolve
with the development of novel therapies and the earlier adoption of continuous treatments
into the treatment pathway. Lenalidomide-refractory patients now represent a challenge
with inferior progression free survival (PFS) reported to subsequent treatments. We
therefore sought to describe the natural history of MM patients following lenalidomide in
the real world.
Methods: This was a retrospective cohort review of patients with relapsed MM who
received lenalidomide-based treatments in the U.K. Data were collected for
demographics, subsequent therapies, treatment responses, survival outcomes and
clinical trial enrollment.
Results: 198 patients received lenalidomide-based treatments at a median of 2 prior lines
of therapy at a median of 41 months (range 0.5-210) from diagnosis. 114 patients (72% of
158 evaluable) became refractory to lenalidomide. The overall survival (OS) after
lenalidomide failure was 14.7 months having received between 0-6 subsequent lines of
therapy. Few deep responses were observed with subsequent treatments and the PFS to
each further line was < 7 months. There was a steep reduction in numbers of patients able
to receive further treatment, with an associated increase in number of deaths. The OS of
patients progressing on lenalidomide who did not enter a clinical trial incorporating novel
agents was very poor (8.8 months versus 30 months, p 0.0002), although the trials group
were a biologically fitter group. Conclusion: These data demonstrate the poor outcomes of patients failing lenalidomidebased
treatments in the real world, the highlight need for more effective treatments
DTâPACE/ESHAP chemotherapy regimens as salvage therapy for multiple myeloma prior to autologous stem cell transplantation
Routine use of novel agents to treat newly diagnosed and relapsed multiple myeloma (MM) produces high response rates and improved survival. However, 15â20% of patients have suboptimal responses and their management remains challenging.1 Traditional regimens, such as DTâPACE (dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide) and ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) are employed in patients with relapsed/refractory (RR) disease, and may bridge patients to autologous stem cell transplantation (ASCT).2-4 Originally developed to improve responses to traditional chemotherapy regimens, and enable stem cell mobilization,5-7 the role of infusional regimens in the context of novel agents is unclear, especially as recently reported series indicate relatively poor outcomes.8, 9 These regimens can be associated with significant toxicity,2 placing a burden on healthcare resources.10
We undertook a singleâcentre retrospective analysis to assess the role of infusional regimens in RR MM patients to explore and identify features associated with clinical benefit. Relevant clinical information was obtained from electronic records. Overall response rate (ORR) and cytogenetic risk were assessed as per International Myeloma Working Group (IMWG) criteria (Table I).11 [Progressionâfree (PFS) and overall survival (OS) were estimated using KaplanâMeier and Cox regression methods (timeâdependent where appropriate)]
Biotrickling filtration of isopropanol under intermittent loading conditions
This paper investigates the removal of isopropanol by gas phase biotrickling filtration. Two plastic packing materials, one structured and one random, have been evaluated in terms of oxygen mass transfer and isopropanol removal efficiency (RE). Oxygen mass transfer experiments were performed at gas velocities of 104 and 312 m h-1
and liquid velocities between 3 and 33 m h-1. Both materials showed
similar mass transfer coefficients up to liquid velocities of 15 m h-1. At greater liquid velocities, the structured packing exhibited greater oxygen mass transfer coefficients. Biotrickling filtration experiments
were carried out at inlet loads (IL) from 20 to 65 g C m-3
h -1
and empty bed residence times (EBRT) from
15 14 to 160 s. To simulate typical industrial emissions, intermittent isopropanol loading (16 h/day, 5
16 day/week) and intermittent spraying frequency (15 min/1.5 hours) were applied. Maximum elimination
capacity (EC) of 51 g C m-3
h
-1
has been obtained for the random packing (IL of 65 g C m-3
h
-1
17 , EBRT of
18 50 s). The decrease in irrigation frequency to 15 min every 3 hours caused a decrease in the outlet
emissions from 86 to 59 mg C Nm-3
(inlet of 500 mg C Nm-3). The expansion of spraying to night and
weekend periods promoted the degradation of the isopropanol accumulated in the water tank during the
day, reaching effluent concentrations as low as 44 mg C Nm-3. After a 7 week starvation period, theperformance was recovered in less than 10 days, proving the robustness of the proces
COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss
Background: Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. Methods: A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Results: Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Conclusions: Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here
Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study
Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) â a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and endâorgan damage. To date, carfilzomibâassociated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial. The first three occurred during maintenance singleâagent carfilzomib, two occurred at induction with carfilzomib given with cyclophosphamide and dexamethasone (KCd) and three occurred during KCd consolidation. At TMA presentation 6/8 were hypertensive; 7/8 had acute kidney injury and in three, renal impairment persisted after resolution of TMA in other respects. The mechanism of carfilzomibâassociated TMA remains unclear, though patients with known hypertension seem particularly susceptible. Given the first three cases occurred during maintenance after a longer than fiveâweek treatment break, a protocol amendment was instituted with: aggressive hypertension management, carfilzomib stepâup dosing (20 mg/m2 on day 1) at start of maintenance before dose escalation to 56 mg/m2 maximum, and adding 10 mg dexamethasone as premedication to maintenance carfilzomib infusions. No further TMA events occurred during maintenance following this amendment and the TMA incidence reduced from 4·2 to 1·6 per 1 000 patient cycles
Deferred autologous stem cell transplantation in systemic AL amyloidosis
High-dose melphalan with autologous stem cell transplantation (ASCT) can induce durable haematological and organ responses in systemic AL amyloidosis (AL). Stringent selection criteria have improved safety of ASCT in AL but most patients are transplant-ineligible. We report our experience of deferred ASCT in AL patients who were transplant-ineligible at presentation but had improvements in organ function after induction chemotherapy, enabling them to undergo ASCT. Twenty-two AL patients underwent deferred ASCT from 2011 to 2017. All had serial organ function and clonal response assessment. Organ involvement and responses were defined by amyloidosis consensus criteria. All patients were transplant-ineligible at presentation, predominantly due to advanced cardiac involvement. All received bortezomib-based therapy, with 100% haematologic response (86% complete response (CR)/very good partial response (VGPR)), enabling reversal of ASCT exclusion criteria. Patients underwent deferred ASCT for haematologic progression (45%) or consolidation (55%). There was no transplant-related mortality. Haematologic responses post-ASCT: CR 50%, VGPR 27%, PR 18%, non-response 5%. In all, 85.7% achieved cardiac responses. Median overall survival (OS) was not reached. Median progression-free survival (PFS) was 54 months. This selected cohort achieved excellent haematologic responses, organ responses, PFS and OS with deferred ASCT. If larger studies confirm these findings, this may widen the applicability of ASCT in AL
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