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Summary Background WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90–70–90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)—a one-third reduction in premature mortality from non-communicable diseases by 2030. Methods The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10–14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions. Findings In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9–14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1–0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3–37·8), averting 300 000 (300 000–400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4–66·1), averting 4·8 million (4·1–4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0–89·3), averting 13·3 million (13·1–13·6) deaths (with once-lifetime screening), or by 92·3% (88·4–93·0), averting 14·6 million (14·1–14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6–89·9), averting 45·8 million (44·7–46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0–98·0), averting 60·8 million (60·2–61·2) deaths (with once-lifetime screening), or by 98·6% (96·5–98·6), averting 62·6 million (62·1–62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45–55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29–34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30–69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4–37·9) by 2030, 96·2% (94·3–96·8) by 2070, and 98·6% (96·9–98·8) by 2120. Interpretation These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives. Funding WHO, UNDP, UN Population Fund, UNICEF–WHO–World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Quebec–Sante.

Summary Background The WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination. Methods The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions. Findings Girls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4–19·8) to 2·1 (2·0–2·6) cases per 100 000 women-years over the next century (89·4% [86·2–90·1] reduction), and to avert 61·0 million (60·5–63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6–1·6) cases per 100 000 women-years (96·7% [91·3–96·7] reduction) and averted an extra 12·1 million (9·5–13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58–65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89–100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37–99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71–100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11–31 years. Long-term vaccine protection was required for elimination. Interpretation Predictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden. Funding WHO, UNDP, UN Population Fund, UNICEF–WHO–World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Quebec–Sante, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.

Ambient Assisted Living (AAL) in general and Activity Recognition (AR) in particular are active fields of research that aim at assisting people in their Activities of Daily Living (ADL). In recent years, we have seen an increased interest in their applicability to the rural seniors who are slowly losing their autonomy due to aging and chronic diseases. One research venue is to aggregate and seek for correlations between the physiological data that serves to monitor the health of the elderly, their ADLs, their movements and any other data that may be collected about their immediate environment. In this paper, we are tackling the possibility of developing a non-intrusive and affordable system based on embedded health, movement, activity and location sensors. Furthermore, we discuss the main concepts behind the creation of a layered, flexible and highly modular architecture that focuses on how the integration of newly combined sensor data can be achieved. Using a mobile phone application prototype, our work has shown that we can integrate two non-invasive technologies that are not necessarily the newest, but the most affordable, scalable and ready to be deployed in real life settings.

Objective Previous HPV models have only included genital transmission, when evidence suggests that transmission between several anatomical sites occurs. We compared model predictions of population-level HPV vaccination effectiveness against genital HPV16 infection in women, using a 1) uni-site (genital site), and a 2) multi-site model (genital and one extragenital site). Methods We developed a uni-site and a multi-site deterministic HPV transmission model, assuming natural immunity was either site-specific or systemic. Both models were calibrated to genital HPV16 prevalence (5%–7.5%), whilst the multi-site model was calibrated to HPV16 prevalence representative of oral (0%–1%) and anal (1%–7.5%) sites. For each model, we identified 2500 parameter sets that fit endemic genital and extragenital prevalences within pre-specified target ranges. In the Base-case analysis, vaccination was girls-only with 40% coverage. Vaccine efficacy was 100% for all sites with lifetime protection. The outcome was the relative reduction in genital HPV16 prevalence among women at post-vaccination equilibrium (RRprev). RRprev was stratified by extragenital prevalence pre-vaccination. Results Under assumptions of site-specific immunity, RRprev with the multi-site model was generally greater than with the uni-site model. Differences between the uni-site and multi-site models were greater when transmission from the extragenital site to the genital site was high. Under assumptions of systemic immunity, the multi-site and uni-site models yielded similar RRprev in the scenario without immunity after extragenital infection. In the scenario with systemic immunity after extragenital infection, the multi-site model yielded lower predictions of RRprev than the uni-site model. Conclusions Modelling genital-site only transmission may overestimate vaccination impact if extragenital infections contribute to systemic natural immunity or underestimate vaccination impact if a high proportion of genital infections originate from extragenital infections. Under current understanding of heterosexual HPV transmission and immunity, a substantial bias from using uni-site models in predicting vaccination effectiveness against genital HPV infection is unlikely to occur.

Background We conducted a systematic review of mathematical models of transmission dynamic of Clostridium difficile infection (CDI) in healthcare settings, to provide an overview of existing models and their assessment of different CDI control strategies. Methods We searched MEDLINE, EMBASE and Web of Science up to February 3, 2016 for transmission-dynamic models of Clostridium difficile in healthcare settings. The models were compared based on their natural history representation of Clostridium difficile, which could include health states (S-E-A-I-R-D: Susceptible-Exposed-Asymptomatic-Infectious-Resistant-Deceased) and the possibility to include healthcare workers and visitors (vectors of transmission). Effectiveness of interventions was compared using the relative reduction (compared to no intervention or current practice) in outcomes such as incidence of colonization, CDI, CDI recurrence, CDI mortality, and length of stay. Results Nine studies describing six different models met the inclusion criteria. Over time, the models have generally increased in complexity in terms of natural history and transmission dynamics and number/complexity of interventions/bundles of interventions examined. The models were categorized into four groups with respect to their natural history representation: S-A-I-R, S-E-A-I, S-A-I, and S-E-A-I-R-D. Seven studies examined the impact of CDI control strategies. Interventions aimed at controlling the transmission, lowering CDI vulnerability and reducing the risk of recurrence/mortality were predicted to reduce CDI incidence by 3–49%, 5–43% and 5–29%, respectively. Bundles of interventions were predicted to reduce CDI incidence by 14–84%. Conclusions Although CDI is a major public health problem, there are very few published transmission-dynamic models of Clostridium difficile. Published models vary substantially in the interventions examined, the outcome measures used and the representation of the natural history of Clostridium difficile, which make it difficult to synthesize results and provide a clear picture of optimal intervention strategies. Future modeling efforts should pay specific attention to calibration, structural uncertainties, and transparent reporting practices.

Energy-phase coupling inside f-2f nonlinear interferometers poses stringent limits on the tolerable pulse-to-pulse energy fluctuations of phase stable laser systems. Here we report a coupling coefficient of −220±20 mrad per 1% energy increase at 800 nm. We also report coefficients from +320 to +820 mrad per 1% energy increase in the 1140–1550 nm (signal) range. Finally, we report coefficients from −180 to +30 mrad per 1% energy variation in the 1636–1940 nm range.

We have used laser pulses with a temporally shaped polarization to demonstrate the multiphoton excitation of the xenon 5g state within a subcycle of a laser pulse. Our polarization gated laser pulses are composed of circularly polarized sections at the leading and trailing edges of the pulse and of an experimentally defined linearly polarized central part. Only the linear part (the gate) of the pulse can excite neutral xenon in the 5g state. The transition cannot be driven with circularly polarized light because the number of photons needed would cause a violation of selection rules for the change of the magnetic quantum number. We show that the linearly polarized central part can be reduced to a subcycle pulse. This allows us to study excitation with an effective pulse as short as 2.3 fs at 800 nm. Electron imaging spectroscopy has been used to visualize the presence of excited states as a function of the pulse duration of the gate.

We demonstrate an alternative approach for attosecond polarization gating. A setup composed of four quartz wedges and a quarter-wave plate allows an easy adjustment of the temporal gate-width and of the total dispersion. A numerical simulation of the pulse propagation beyond the carrier-envelope approximation enables a calibration of the setup and provides a flexible choice of the desired temporal polarization. An electron imaging spectrometer is used to measure the electron momentum distribution resulting from the ionization of xenon with our optical gated laser pulses. This allows us to measure the orientation of the polarization plane in the most intense temporal slice of the laser pulse. We compare the experimental results to theory and we numerically show the robustness of the method against non-ideal laser parameters.

We present a modelocked femtosecond thin disk laser that generates pulse energies beyond the 10-μJ limit. We discuss the first photoelectron imaging spectroscopy measurements at multi-megahertz repetition rate, which is advantageous due to high signal-to-noise ratio and reduced measurement time. A maximum peak intensity of 6·1013 W/cm2 was achieved at 14 MHz repetition rate.

We achieve 10-microjoule pulse energies directly from a femtosecond laser oscillator. We underline its suitability for high field experiments at multi-megahertz repetition rate by demonstrating the first electron spectroscopy measurements driven by an oscillator.

Optimal pulse compression following spectral broadening in a noble gas-filled hollow core fiber is a critical step towards producing isolated attosecond pulses. Here we present a systematic pulse shaping method based on the optimal selection of chirped mirrors and on the optimization of their angle of incidence. Feedback from second harmonic frequency resolved optical gating measurements is used to compute the optimal chirped mirror configuration of the next iteration in a genetic algorithm. Sub-5 fs pulses were achieved after a few iterations.

We demonstrate a four-wave mixing (FWM) technique to measure near- and mid-infrared (IR) laser pulse shapes in time domain. Few cycle 800 nm laser pulses were synchronized with the IR pulse and focused colinearly to generate a plasma filament in air. Second harmonic radiation around 400 nm was generated through FWM, with a yield proportional to the IR pulse intensity. Excellent signal to noise ratio was observed from 2.1 μm to 18 μm. With proper phase stabilization of the IR beam, this technique is a promising step toward direct electric field sensing of near-IR pulses in air.