Making optical atomic clocks more stable with 10−1610^{-16} level laser stabilization

The superb precision of an atomic clock is derived from its stability. Atomic clocks based on optical (rather than microwave) frequencies are attractive because of their potential for high stability, which scales with operational frequency. Nevertheless, optical clocks have not yet realized this vast potential, due in large part to limitations of the laser used to excite the atomic resonance. To address this problem, we demonstrate a cavity-stabilized laser system with a reduced thermal noise floor, exhibiting a fractional frequency instability of $2 \times 10^{-16}$. We use this laser as a stable optical source in a Yb optical lattice clock to resolve an ultranarrow 1 Hz transition linewidth. With the stable laser source and the signal to noise ratio (S/N) afforded by the Yb optical clock, we dramatically reduce key stability limitations of the clock, and make measurements consistent with a clock instability of $5 \times 10^{-16} / \sqrt{\tau}$

Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US$11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings

Generation of Ultrastable Microwaves via Optical Frequency Division

There has been increased interest in the use and manipulation of optical fields to address challenging problems that have traditionally been approached with microwave electronics. Some examples that benefit from the low transmission loss, agile modulation and large bandwidths accessible with coherent optical systems include signal distribution, arbitrary waveform generation, and novel imaging. We extend these advantages to demonstrate a microwave generator based on a high-Q optical resonator and a frequency comb functioning as an optical-to-microwave divider. This provides a 10 GHz electrical signal with fractional frequency instability <8e-16 at 1 s, a value comparable to that produced by the best microwave oscillators, but without the need for cryogenic temperatures. Such a low-noise source can benefit radar systems, improve the bandwidth and resolution of communications and digital sampling systems, and be valuable for large baseline interferometry, precision spectroscopy and the realization of atomic time

Introduction: looking beyond the walls

In its consideration of the remarkable extent and variety of non-university researchers, this book takes a broader view of ‘knowledge’ and ‘research’ than in the many hot debates about today’s knowledge society, ‘learning age’, or organisation of research. It goes beyond the commonly held image of ‘knowledge’ as something produced and owned by the full-time experts to take a look at those engaged in active knowledge building outside the university walls

Estimation of changes in the force of infection for intestinal and urogenital schistosomiasis in countries with Schistosomiasis Control Initiative-assisted programmes

The last decade has seen an expansion of national schistosomiasis control programmes in Africa based on large-scale preventative chemotherapy. In many areas this has resulted in considerable reductions in infection and morbidity levels in treated individuals. In this paper, we quantify changes in the force of infection (FOI), defined here as the per (human) host parasite establishment rate, to ascertain the impact on transmission of some of these programmes under the umbrella of the Schistosomiasis Control Initiative (SCI)

Evidence for solar cycles in a late Holocene speleothem record from Dongge Cave, China

The association between solar activity and Asian monsoon (AM) remains unclear. Here we evaluate the possible connection between them based on a precisely-dated, high-resolution speleothem oxygen isotope record from Dongge Cave, southwest China during the past 4.2 thousand years (ka). Without being adjusted chronologically to the solar signal, our record shows a distinct peak-to-peak correlation with cosmogenic nuclide 14C, total solar irradiance (TSI) and sunspot number (SN) at multi-decadal to centennial timescales. Further cross-wavelet analyses between our calcite δ18O and atmospheric 14C show statistically strong coherence at three typical periodicities of ~80, 200 and 340 years, suggesting important roles of solar activities in modulating AM changes at those timescales. Our result has further indicated a better correlation between our calcite δ18O record and atmospheric 14C than between our record and TSI. This better correlation may imply that the Sun–monsoon connection is dominated most likely by cosmic rays and oceanic circulation (both associated to atmospheric 14C), instead of the direct solar heating (TSI)

Why is it difficult to implement e-health initiatives? A qualitative study

&lt;b&gt;Background&lt;/b&gt; The use of information and communication technologies in healthcare is seen as essential for high quality and cost-effective healthcare. However, implementation of e-health initiatives has often been problematic, with many failing to demonstrate predicted benefits. This study aimed to explore and understand the experiences of implementers - the senior managers and other staff charged with implementing e-health initiatives and their assessment of factors which promote or inhibit the successful implementation, embedding, and integration of e-health initiatives.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; We used a case study methodology, using semi-structured interviews with implementers for data collection. Case studies were selected to provide a range of healthcare contexts (primary, secondary, community care), e-health initiatives, and degrees of normalization. The initiatives studied were Picture Archiving and Communication System (PACS) in secondary care, a Community Nurse Information System (CNIS) in community care, and Choose and Book (C&#38;B) across the primary-secondary care interface. Implementers were selected to provide a range of seniority, including chief executive officers, middle managers, and staff with 'on the ground' experience. Interview data were analyzed using a framework derived from Normalization Process Theory (NPT).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; Twenty-three interviews were completed across the three case studies. There were wide differences in experiences of implementation and embedding across these case studies; these differences were well explained by collective action components of NPT. New technology was most likely to 'normalize' where implementers perceived that it had a positive impact on interactions between professionals and patients and between different professional groups, and fit well with the organisational goals and skill sets of existing staff. However, where implementers perceived problems in one or more of these areas, they also perceived a lower level of normalization.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Implementers had rich understandings of barriers and facilitators to successful implementation of e-health initiatives, and their views should continue to be sought in future research. NPT can be used to explain observed variations in implementation processes, and may be useful in drawing planners' attention to potential problems with a view to addressing them during implementation planning

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Feasibility and Coverage of Implementing Intermittent Preventive Treatment of Malaria in Pregnant women Contacting Private or Public Clinics in Tanzania: Experience-based Viewpoints of Health Managers in Mkuranga and Mufindi districts.

Evidence on healthcare managers' experience on operational feasibility of malaria intermittent preventive treatment for malaria during pregnancy (IPTp) using sulphadoxine-pyrimethamine (SP) in Africa is systematically inadequate. This paper elucidates the perspectives of District Council Health Management Team (CHMT)s regarding the feasibility of IPTp with SP strategy, including its acceptability and ability of district health care systems to cope with the contemporary and potential challenges. The study was conducted in Mkuranga and Mufindi districts. Data were collected between November 2005 and December 2007, involving focus group discussion (FGD) with Mufindi CHMT and in-depth interviews were conducted with few CHMT members in Mkuranga where it was difficult to summon all members for FGD. Participants in both districts acknowledged the IPTp strategy, considering the seriousness of malaria in pregnancy problem; government allocation of funds to support healthcare staff training programmes in focused antenatal care (fANC) issues, procuring essential drugs distributed to districts, staff remuneration, distribution of fANC guidelines, and administrative activities performed by CHMTs. The identified weaknesses include late arrival of funds from central level weakening CHMT's performance in health supervision, organising outreach clinics, distributing essential supplies, and delivery of IPTp services. Participants anticipated the public losing confidence in SP for IPTp after government announced artemither-lumefantrine (ALu) as the new first-line drug for uncomplicated malaria replacing SP. Role of private healthcare staff in IPTp services was acknowledged cautiously because CHMTs rarely supplied private clinics with SP for free delivery in fear that clients would be required to pay for the SP contrary to government policy. In Mufindi, the District Council showed a strong political support by supplementing ANC clinics with bottled water; in Mkuranga such support was not experienced. A combination of health facility understaffing, water scarcity and staff non-adherence to directly observed therapy instructions forced healthcare staff to allow clients to take SP at home. Need for investigating in improving adherence to IPTp administration was emphasised. High acceptability of the IPTp strategy at district level is meaningless unless necessary support is assured in terms of number, skills and motivation of caregivers and availability of essential supplies